XXIII.2

2. References

The complete bibliography of the Food Sources book: the citation markers found in the chapters can be traced back here to the original scientific sources.

What is in the bibliography?

This appendix holds the book's complete bibliography in one place: every scientific reference cited in any chapter of the volume. The `[12]`, `[325]` and other numbers in the body text point to the entries listed below — the numbering runs across the entire book, so the same `[N]` reference number always points to the same source. The vast majority of the listed publications appeared in peer-reviewed journals and are also findable in indexed databases (PubMed/NCBI, Crossref), from reputable professional publishers.

Why is there a summary under each entry?

Under each reference there is a 5–6 sentence synopsis. This is not the article's official abstract but a short, plain-language summary presenting the study's background, the method used, the main result, and its clinical or practical significance. Its purpose is to let the reader quickly decide whether the full publication is worth reading and whether it fits their own question or the patient's situation. The summaries help you orient yourself even without direct access to the full text.

How to use it?

Under each entry you will find the "Cited in" line: clicking the chapter number shown there returns you to the part of the book where the source is cited. Within that chapter, clicking the `[N]` marker brings the reader here, to the bibliography — so you can move freely in both directions. Clicking the reference marked "Link" opens the publication on the publisher's or NCBI's site, where — if the article is freely accessible (open access) — the full text can also be read.

References

[85] Holscher, H. D. Dietary fiber and prebiotics and the gastrointestinal microbiota. Gut Microbes. 2017. Link

Review of dietary strategies — fibre and prebiotic consumption — to modulate the gastrointestinal microbiota and its metabolic function for health benefit. Most complex carbohydrates and plant polysaccharides are not digested by human enzymes but are fermented by gut microbes into SCFAs and other bioactive metabolites. The review summarizes mechanisms and clinical applications and frames prebiotic intake as a primary lever for microbiome-targeted disease prevention and treatment.

[105] Bourrie BCT, Willing BP, Cotter PD. The Microbiota and Health Promoting Characteristics of the Fermented Beverage Kefir. Front Microbiol. 2016. Link

Review of kefir, a complex fermented dairy product produced by symbiotic fermentation of milk by lactic acid bacteria and yeasts embedded in a kefir grain. Kefir has been associated with reduced cholesterol and ACE inhibition, antimicrobial activity, tumor suppression, accelerated wound healing, and immunomodulation (including allergy and asthma alleviation). The review synthesizes evidence on kefir's bioactive components and proposes it as a candidate functional food for cardiometabolic and immune health.

[106] Wastyk HC, Fragiadakis GK, Perelman D et al. Gut-microbiota-targeted diets modulate human immune status. Cell. 2021. Link

17-week randomized prospective trial (n=18/arm) in healthy adults comparing high-fibre versus high-fermented-food diets with multi-omics microbiome and host immune profiling. The high-fibre diet increased microbiome-encoded glycan-degrading CAZymes despite stable diversity. The high-fermented-food diet increased microbiome diversity and decreased multiple inflammatory markers. Findings demonstrate diet-specific microbiome–immune effects and support fermented foods as a strong, diversity-promoting modulator of the gut–immune axis.

[112] Marsh AJ, O'Sullivan O, Hill C, Ross RP, Cotter PD. Sequence-based analysis of the bacterial and fungal compositions of multiple kombucha (tea fungus) samples. Food Microbiol. 2014. Link

Review of kombucha, a sweetened tea fermented by a symbiosis of bacteria and yeast embedded in a cellulosic pellicle, producing ethanol, CO2, organic acids (gluconic, acetic, lactic), and bioactive metabolites. The microbial composition has long been the focus of investigation. The review summarizes current evidence on kombucha's microbial ecology and proposed health effects, framing it as a fermented beverage with plausible but incompletely characterized functional properties.

[126] Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev. 2001. Link

Resistant starch (RS) and nonstarch polysaccharides (NSP), the major components of dietary fibre, are fermented by human colonic bacteria to short-chain fatty acids — primarily acetate, propionate and butyrate. SCFAs stimulate colonic blood flow and fluid/electrolyte uptake; butyrate is the preferred colonocyte substrate and supports a normal colonocyte phenotype. Fermentation of certain RS types preferentially favours butyrate production, providing a mechanistic basis for the colon-health benefits of fibre-rich diets.

[768] Sonnante G et al. The Domestication of Artichoke and Cardoon: From Roman Times to the Genomic Age2007;100(5):1095–1100. Annals of Botany. Link

A botanical/genomic review on the domestication of artichoke (Cynara) and cardoon, spanning from Roman times to the genomic age (Annals of Botany).

[769] . European Medicines Agency (HMPC) 2011. Community herbal monograph on Cynara scolymus L., folium. 2011. Link

A European Medicines Agency (EMA/HMPC) community herbal monograph on artichoke leaf, Cynara scolymus L. folium.

[770] Holtmann G et al. Efficacy of artichoke leaf extract in functional dyspepsia: a six-week placebo-controlled, double-blind, multicentre trial2003;18(11):1099–1105. Aliment Pharmacol Ther. Link

BACKGROUND: This study aimed to assess the efficacy of artichoke leaf extract (ALE) in the treatment of patients with functional dyspepsia (FD). METHODS: In a double-blind, randomized controlled trial (RCT), 247 patients with functional dyspepsia were recruited and treated with either a commercial ALE preparation (2 x 320 mg plant extract t.d.s.) or a placebo. The primary efficacy variable was the sum score of the patient's weekly rating of the overall change in dyspeptic symptoms (four-point scale). Secondary variables were the scores of each dyspeptic symptom and the quality of life (QOL) as assessed by the Nepean Dyspepsia Index (NDI). RESULTS: Two hundred and forty-seven patients were enrolled, and data from 244 patients (129 active treatment, 115 placebo) were suitable for inclusion in the statistical analysis (intention-to-treat). The overall symptom improvement over the 6 weeks of treatment was significantly greater with ALE than with the placebo (8.3 +/- 4.6, vs. 6.7 +/- 4.8, P < 0.01).

[771] Bundy R et al. Artichoke leaf extract reduces plasma lipids in mild–moderate hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial2008;15(9):668–675. Phytomedicine. Link

Cardiovascular diseases are the chief causes of death in the UK, and are associated with high circulating levels of total cholesterol in the plasma. Artichoke leaf extracts (ALEs) have been reported to reduce plasma lipids levels, including total cholesterol, although high quality data is lacking. The objective of this trial was to assess the effect of ALE on plasma lipid levels and general well-being in otherwise healthy adults with mild to moderate hypercholesterolemia. 131 adults were screened for total plasma cholesterol in the range 6.0-8.0 mmol/l, with 75 suitable volunteers randomised onto the trial. Volunteers consumed 1280 mg of a standardised ALE, or matched placebo, daily for 12 weeks. Plasma total cholesterol decreased in the treatment group by an average of 4.2\% (from 7.16 (SD 0.62) mmol/l to 6.86 (SD 0.68) mmol/l) and increased in the control group by an average of 1.9\% (6.90 (SD 0.49) mmol/l to 7.03 (0.61) mmol/l), the difference between groups being statistically significant (p=0.025). No significant differences between groups were observed for LDL cholesterol, HDL cholesterol or triglyceride levels.

[772] Costabile A et al. A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke in healthy human subjects2010;104(7):1007–1017. Br J Nutr. Link

There is growing interest in the use of inulins as substrates for the selective growth of beneficial gut bacteria such as bifidobacteria and lactobacilli because recent studies have established that their prebiotic effect is linked to several health benefits. In the present study, the impact of a very-long-chain inulin (VLCI), derived from globe artichoke (Cynara scolymus), on the human intestinal microbiota compared with maltodextrin was determined. A double-blind, cross-over study was carried out in thirty-two healthy adults who were randomised into two groups and consumed 10 g/d of either VLCI or maltodextrin, for two 3-week study periods, separated by a 3-week washout period. Numbers of faecal bifidobacteria and lactobacilli were significantly higher upon VLCI ingestion compared with the placebo. Additionally, levels of Atopobium group significantly increased, while Bacteroides-Prevotella numbers were significantly reduced. No significant changes in faecal SCFA concentrations were observed.

[773] Feiden T et al. Bioactive Compounds from Artichoke and Application Potential2023;61(3):312–327. Food Technol Biotechnol. Link

Cynara cardunculus L. var. scolymus, known as the artichoke, originated in the Mediterranean region and is now cultivated in several countries. The artichoke has leaves, a stem, and a head, also called a floral capitulum, covered with green and pointed bracts. It is rich in polyphenols, flavonoids, anthocyanins, phenolic compounds, inulin, coumarins, terpenes, dietary fibre, enzymes, polysaccharides, minerals and vitamins, and therefore has a wide range of uses, including in the food industry, medicine and biofuels. Several studies have shown that artichokes have properties such as antioxidant, anti-inflammatory, antimicrobial, anticancer, hypocholesterolaemic, anti-HIV, cardioprotective, hepatoprotective and lipid-lowering effects. The aim of this study is to provide a literature review on the phytochemical composition, bioactivity and applications, focusing on the methods of extraction, purification and concentration of enzymes present in artichoke.

[774] Holgado F et al. In vitro fermentability of globe artichoke by-product byand Bifidobacterium bifidum. Bioact Carbohydr Diet Fibre 2021;26:100286. Lactobacillus acidophilus. 2021. Link

An in vitro study examining the fermentability of globe artichoke by-product by Lactobacillus acidophilus and Bifidobacterium bifidum (Bioact Carbohydr Diet Fibre).

[775] EFSA NDA Panel. Scientific Opinion on chicory inulin and maintenance of normal defecation2015;13(1):3951. EFSA Journal. Link

The EFSA NDA Panel assessed the scientific substantiation of a health claim (application by BENEO-Orafti S.A.) pursuant to Article 13.5 of Regulation (EC) No 1924/2006. Based on six studies (86 subjects in total), the Panel established a cause-and-effect relationship between consumption of "native chicory inulin" and maintenance of normal defecation by increasing stool frequency. To obtain the claimed effect, at least 12 g of native chicory inulin should be consumed daily.

[776] Glibowski P, Bukowska A. The effect of pH, temperature and heating time on inulin chemical stability2011;10(2):189–196. Acta Sci Pol Technol Aliment. Link

A food-technology study examining the chemical stability of inulin as a function of pH, temperature and heating time (Acta Sci Pol Technol Aliment).

[777] . Monash UniversityMonash FODMAP database. High and Low FODMAP foods. Link

The Monash University FODMAP database, classifying foods as high or low in FODMAP content.

[778] USDA FoodData Central. Avocados, raw, all commercial varieties. USDA Agricultural Research Service. Link

USDA FoodData Central food-composition data entry for raw avocado (all commercial varieties), from the USDA Agricultural Research Service.

[779] Thompson SV et al. Avocado consumption alters gastrointestinal bacteria abundance and microbial metabolites in adults with overweight or obesity2021;151(4):753–762. J Nutr. Link

Randomized controlled human nutrition trial (J Nutr) examining how avocado consumption alters gastrointestinal bacterial abundance and microbial metabolites in adults with overweight or obesity.

[780] Edwards CG et al. Effects of one avocado per day on the microbiota: 26-week HAT-ancillary RCT. 2025. . 2025. Link

A randomized controlled trial (HAT-ancillary RCT) examining the effect of consuming one avocado per day on the gut microbiota over 26 weeks.

[781] Unlu NZ et al. Carotenoid absorption from salad and salsa by humans is enhanced by the addition of avocado or avocado oil2005;135(3):431–436. J Nutr. Link

Dietary lipids are hypothesized to be an important factor for carotenoid bioavailability. However, most carotenoid-rich fruits and vegetables are low in lipids. The objective of this study was to assess whether the addition of avocado fruit as a lipid source enhances carotenoid absorption in humans. Healthy subjects (n = 11/study) were recruited for 2 crossover, postprandial studies. The effect of avocado addition (150 g) to salsa on lycopene and beta-carotene absorption was examined in Study 1, and the absorption of lutein, alpha-carotene, and beta-carotene from salad in Study 2. Furthermore, the effects of avocado dose (75 vs. 150 g containing 12 vs. 24 g lipid, respectively) and of lipid source (avocado fruit vs. avocado oil) on carotenoid absorption were examined in Study 2.

[782] Galindo-Tovar ME et al. Some aspects of avocado (Persea americana Mill.) diversity and domestication in Mesoamerica2008. Genet Resour Crop Evol. Link

A study on aspects of avocado (Persea americana Mill.) diversity and its domestication in Mesoamerica (Genet Resour Crop Evol).

[783] . Monash University2024. High and Low FODMAP foods — avocado update (perseitol). Link

The 2024 Monash University FODMAP database update for avocado (perseitol), with high/low FODMAP classification.

[784] Scott TM et al. Avocado consumption increases macular pigment density: a randomized controlled trial2017. Nutrients. Link

Lutein is selectively incorporated into the macula and brain. Lutein levels in the macula (macular pigment; MP) and the brain are related to better cognition. MP density (MPD) is a biomarker of brain lutein. Avocados are a bioavailable source of lutein. This study tests the effects of the intake of avocado on cognition. This was a six-month, randomized, controlled trial.

[785] Pacheco LS et al. Avocado consumption and body weight in NHANES adults 2022. J Am Heart Assoc. 2022.

An epidemiological analysis of the association between avocado consumption and body weight in NHANES adults (J Am Heart Assoc).

[786] Gibson GR et al. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics2017;14(8):491–502. Nat Rev Gastroenterol Hepatol. Link

The ISAPP (International Scientific Association for Probiotics and Prebiotics) consensus statement on the definition and scope of prebiotics (Nat Rev Gastroenterol Hepatol).

[787] EFSA NDA Panel. Scientific Opinion on chicory inulin and maintenance of normal defecation2015;13(1):3951. EFSA Journal. Link

[788] Roberfroid M. Prebiotics: the concept revisited2007;137(3 Suppl 2):830S–837S. J Nutr. Link

A prebiotic is "a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-being and health." Today, only 2 dietary nondigestible oligosaccharides fulfill all the criteria for prebiotic classification. The daily dose of the prebiotic is not a determinant of the prebiotic effect, which is mainly influenced by the number of bifidobacteria/g in feces before supplementation of the diet with the prebiotic begins. The ingested prebiotic stimulates the whole indigenous population of bifidobacteria to growth, and the larger that population, the larger is the number of new bacterial cells appearing in feces. The "dose argument" is thus not supported by the scientific data: it is misleading for consumers and should not be allowed. A prebiotic index is proposed, defined as "the increase in the absolute number of bifidobacteria expressed divided by the daily dose of prebiotic ingested."

[789] Wang M et al. Bifidogenic effect of inulin-type fructans: a systematic review 2019. Br J Nutr. 2019.

A systematic review of the bifidogenic effect of inulin-type fructans (Br J Nutr).

[790] Sun W et al. Asparagus polysaccharides: structure and biological activity review 2022. Food Chem. 2022.

A review of the structure and biological activity of asparagus polysaccharides (Food Chem).

[792] Mitchell SC. Food idiosyncrasies: beetroot and asparagus2001;29(4 Pt 2):539–543. Drug Metab Dispos. Link

Anecdotal observations scattered throughout the literature have often provided clues to underlying variations in humans' ability to handle dietary chemicals. Beetroot, the red root of the garden beet used extensively as a food source, is known to produce red urine in some people following its ingestion, whereas others appear to be able to eat the vegetable with impunity. Asparagus, a vegetable whose young shoots have been eaten as a delicacy since the times of the Roman Empire, has been associated with the production of a malodorous urine smelling like rotten cabbage. Those who produce this odor assume that everyone does, and those who do not produce it have no idea of its potential olfactory consequences. These two examples, where the population appears divided in its ability to process food products or more precisely the chemicals contained within them, are reviewed in detail in this article.

[793] . Apicius Liber III (Cepuros). De re coquinaria.

Book III (Cepuros) of Apicius's ancient Roman cookbook De re coquinaria, a historical primary source.

[794] EFSA NDA Panel. Scientific Opinion on the substantiation of a health claim related to "native chicory inulin" and maintenance of normal defecation2015;13(1):3951. EFSA Journal. Link

[795] Roberfroid M et al. Dietary modulation of the human colonic microbiota: updating the concept of prebiotics 2010;23(2):164–185. Nutr Res Rev. 2010.

A review on dietary modulation of the human colonic microbiota that updates the concept of prebiotics (Nutr Res Rev).

[796] Cherbut C. Inulin and oligofructose in the dietary fibre concept2002;87 Suppl 2:S159–S162. Br J Nutr. Link

Dietary fibre consists of remnants of edible plant cell polysaccharides and associated substances resistant to hydrolysis by human alimentary enzymes, which may benefit health through a wide range of physiological effects. Inulin and oligofructose are storage carbohydrates found in a number of vegetables, fruits and whole grains. They resist digestion and absorption in the stomach and small intestine of humans, as shown by their almost full recovery at the end of the ileum of healthy or ileostomised volunteers. Inulin and oligofructose thus enter into the large intestine where they are available to fermentation, as demonstrated by increased breath hydrogen. Fermentation of both substrates is complete and no residue is found in human stools. Inulin and oligofructose improve laxation.

[797] Kolida S, Meyer D, Gibson GR. A double-blind placebo-controlled study to establish the bifidogenic dose of inulin in healthy humans2007;61(10):1189–1195. Eur J Clin Nutr. Link

OBJECTIVE: To evaluate the bifidogenic efficacy of two inulin doses in healthy human adults. DESIGN: A double-blind, placebo-controlled, crossover human study. SETTING: Food Microbial Sciences Unit, The University of Reading, Reading, UK. SUBJECTS: Thirty healthy volunteers, 15 men, 15 women (age range 19-35). INTERVENTIONS: Subjects consumed a chocolate drink containing placebo (maltodextrin, 8 g/day), 5 g/day inulin and 8 g/day inulin for a 2-week treatment period. Each treatment was followed by a 1-week washout at the end of which volunteers progressed to the next treatment.

[798] Micka A et al. Effect of consumption of chicory inulin on bowel function in healthy subjects with constipation: a randomized, double-blind, placebo-controlled trial2017;68(1):82–89. Int J Food Sci Nutr. Link

UNLABELLED: Constipation is among the most common health impairments in Western countries. This study aimed to determine the effect of the chicory-derived fermentable dietary fiber Orafti® Inulin on stool frequency in healthy subjects with constipation. The study was conducted according to recent guidance documents for investigating bowel function and used a randomized, double-blind, placebo-controlled, cross-over design with a 2-week wash-out phase. Each study period comprised a run-in phase followed by 4 weeks daily intake of 3 × 4g inulin or maltodextrin (placebo). Forty-four healthy volunteers with constipation documented stool frequency and consistency, gastrointestinal characteristics and quality of life. Consumption of Orafti® Inulin significantly increased stool frequency compared to placebo (median 4.0 [IQR 2.5-4.5] versus 3.0 [IQR 2.5-4.0] stools/week, p = 0.038).

[799] Le Bastard Q et al. The effects of inulin on gut microbial composition: a systematic review of evidence from human studies2020;39(3):403–413. Eur J Clin Microbiol Infect Dis. Link

BACKGROUND: Inulin, consisting of repetitive fructosyl units linked by β(2,1) bonds, is a readily fermentable fiber by intestinal bacteria that generates large quantities of short-chain fatty acids (SCFA). In individuals with constipation, it was reported that inulin ingestion was associated with a significant increase in stool frequency, suggesting a potential impact of inulin on human gut microbiota composition. Progress in high-throughput technologies allow assessment of human-associated microbiomes in terms of diversity and taxonomic or functional composition, and can identify changes in response to a specific supplementation. Hence, to understand the effects of inulin on the human gut microbiome is pivotal to gain insight into their mechanisms of action. METHODS: Here, we conducted a systematic review of human studies in adult individuals showing the effects of inulin on the gut microbiome. We searched in MEDLINE, EMBASE, Web of Science, and Scopus databases for articles in English published in peer-reviewed journals and indexed up until March 2019.

[800] Apolinário AC et al. Inulin-type fructans: a review on different aspects of biochemical and pharmaceutical technology2014;101:368–378. Carbohydr Polym. Link

Inulin is a natural storage polysaccharide with a large variety of food and pharmaceutical applications. It is widely distributed in plants, being present as storage carbohydrate in more than 30,000 vegetable products. Due to their wide distribution in nature and significant role in industry, the extraction, isolation and characterization of inulin-type fructans are gaining attention in recent years. Inulin sources have recently received increasing interest as they are a renewable raw material for the production of bioethanol, fructose syrup, single-cell protein and single cell oil, obtainment of fructooligosaccharides and other useful products. This review focuses on the state-of-the-art of biochemical and pharmaceutical technology of inulin-type fructans.

[802] Slimestad R et al. Onions: a source of unique dietary flavonoids2007;55(25):10067–10080. J Agric Food Chem. Link

Onion bulbs (Allium cepa L.) are among the richest sources of dietary flavonoids and contribute to a large extent to the overall intake of flavonoids. This review includes a compilation of the existing qualitative and quantitative information about flavonoids reported to occur in onion bulbs, including NMR spectroscopic evidence used for structural characterization. In addition, a summary is given to index onion cultivars according to their content of flavonoids measured as quercetin. Only compounds belonging to the flavonols, the anthocyanins, and the dihydroflavonols have been reported to occur in onion bulbs. Yellow onions contain 270-1187 mg of flavonols per kilogram of fresh weight (FW), whereas red onions contain 415-1917 mg of flavonols per kilogram of FW. Flavonols are the predominant pigments of onions.

[803] Galeone C et al. Onion and garlic use and human cancer2006;84(5):1027–1032. Am J Clin Nutr. Link

BACKGROUND: Interest in the potential benefits of allium vegetables, in particular, onion (Allium cepa) and garlic (Allium sativum), has its origin in antiquity, but the details of these benefits are still open to discussion. OBJECTIVE: We investigated the role of allium vegetables in the etiology of various neoplasms. Previous data are scanty and are based mainly on Chinese studies. DESIGN: Using data from an integrated network of Italian and Swiss case-control studies, we analyzed the relation between frequency of onion and garlic use and cancer at several sites. We calculated odds ratios (ORs) by using multivariate logistic regression models that were adjusted for energy intake and other major covariates. RESULTS: Consumption of onions varied between 0-14 and 0-22 portions/wk among cases and controls, respectively.

[804] Suleria HAR et al. Onion: nature protection against physiological threats2015;55(1):50–66. Crit Rev Food Sci Nutr. Link

Onion (Allium cepa L.) is found in various regions of Europe, North America, Asia, and Africa. It is one of the classic examples of Allium species used not only for culinary preparations but also for medicinal purposes. Onion with a variety of purposes is often used as a raw material in many dishes and accepts almost all of the traditions and culture. Owing to its storage characteristics and durability of shipping, onions have been traded more widely than most vegetables. The pungent fractions of garlic are mostly sulfur-containing moieties while its two chemical groups have marked effect on human health. These are flavonoids and ALK (EN)-based cysteine sulfoxides (ACSOs).

[805] Egert S et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects: a double-blind, placebo-controlled cross-over study2009;102(7):1065–1074. Br J Nutr. Link

A double-blind, placebo-controlled cross-over study examining the effect of quercetin on systolic blood pressure and oxidised LDL concentrations in overweight subjects (Br J Nutr).

[807] Kleijnen J, Knipschild P, ter Riet G. Garlic, onions and cardiovascular risk factors: a review of the evidence from human experiments with emphasis on commercially available preparations1989;28(5):535–544. Br J Clin Pharmacol. Link

1. Claims for beneficial effects on cholesterol levels, fibrinolytic activity, and platelet aggregation are attributed both to fresh garlic and onions (or their extracts) and to commercially available preparations. 2. Regarding fresh garlic, the claims have been confirmed, but so far only at very high dosages. 3. For onions and commercially available supplements contradictory results have been reported. 4. All published trials showed severe methodological shortcomings. Some trials were not randomized and/or not blinded whilst this was possible, and in only one of every three studies more than 25 patients participated in each treatment group.

[808] . EMA/HMPCAssessment report. Community herbal monograph on Allium cepa L., bulbus. Link

An EMA/HMPC assessment report and community herbal monograph on onion (Allium cepa L., bulbus).

[809] Reinhart KM et al. The impact of garlic on lipid parameters: a systematic review 2009 (kontextus Allium-családra). Nutr Res Rev. 2009.

A systematic review of the impact of garlic on lipid parameters, in the context of the Allium family (Nutr Res Rev).

[810] Ried K. Garlic lowers blood pressure in hypertensive subjects, improves arterial stiffness and gut microbiota: a review and meta-analysis2020;19(2):1472–1478. Exp Ther Med. Link

Review and meta-analysis (Exp Ther Med) on garlic's blood-pressure-lowering effect in hypertensive subjects and its impact on arterial stiffness and the gut microbiota.

[811] Cavallito CJ, Bailey JH. Allicin, the antibacterial principle of Allium sativum. I. Isolation, physical properties and antibacterial action1944;66:1950–1951. J Am Chem Soc. 1950. Link

A classic chemistry paper on allicin, the antibacterial principle of Allium sativum: its isolation, physical properties and antibacterial action (J Am Chem Soc).

[812] Lawson LD, Hunsaker SM. Allicin bioavailability and bioequivalence from garlic supplements and garlic foods2018;10(7):812. Nutrients. Link

A study on the bioavailability and bioequivalence of allicin from garlic supplements and garlic foods (Nutrients).

[813] Borrelli F et al. Garlic (Allium sativum L.): adverse effects and drug interactions in humans2007;51(11):1386–1397. Mol Nutr Food Res. Link

A review of the adverse effects and drug interactions of garlic (Allium sativum L.) in humans (Mol Nutr Food Res).

[814] Ried K et al. The effect of aged garlic extract on gut microbiota, inflammation, and cardiovascular markers in hypertensives: The GarGIC Trial 2018;5:122. Front Nutr. 2018. Link

The GarGIC Trial was a 12-week double-blind, randomized, placebo-controlled study in 49 participants with uncontrolled hypertension, investigating the effect of Kyolic aged garlic extract (1.2 g/day, containing 1.2 mg S-allylcysteine) on blood pressure, arterial stiffness, inflammatory markers, and gut microbiota. Compared with placebo, the extract significantly reduced blood pressure (by 10 ± 3.6 mmHg systolic and 5.4 ± 2.3 mmHg diastolic) and favorably modulated the gut microbiota, with increased Lactobacillus and Clostridia species. The authors conclude that the extract is effective in lowering blood pressure in uncontrolled hypertension and may improve arterial stiffness, inflammation, and microbial profile.

[815] Piscitelli SC et al. The effect of garlic supplements on the pharmacokinetics of saquinavir2002;34(2):234–238. Clin Infect Dis. Link

Herbal therapies are widely used, but there are few data on their interactions with conventional medications. This study evaluated the effect of garlic supplements on the pharmacokinetics of saquinavir. Ten healthy volunteers received 10 doses of saquinavir (Fortovase) at a dosage of 1200 mg 3 times daily with meals for 4 days on study days 1-4, 22-25, and 36-39, and they received a total of 41 doses of garlic caplets taken 2 times daily on study days 5-25. Blood samples were obtained on study days 4, 25, and 39 for determination of saquinavir plasma pharmacokinetic parameters. In the presence of garlic, the mean saquinavir area under the curve (AUC) during the 8-h dosing interval decreased by 51\%, trough levels at 8 h after dosing decreased by 49\%, and the mean maximum concentrations (Cmax) decreased by 54\%. After the 10-day washout period, the AUC, trough, and Cmax values returned to 60\%-70\% of their values at baseline.

[816] . EMA/HMPC 2017. Community herbal monograph on Allium sativum L., bulbus. 2017. Link

An EMA/HMPC community herbal monograph on garlic (Allium sativum L., bulbus).

[817] . Linus Pauling InstituteOregon State University. Garlic and organosulfur compounds. Link

A Linus Pauling Institute (Oregon State University) review resource on garlic and organosulfur compounds.

[818] Bystrická J et al. Bioactive compounds in different parts of leek (Allium ampeloprasum L.) 2015;4(Spec. issue 3):39–42. J Microbiol Biotechnol Food Sci. 2015.

A study on the bioactive compounds in different parts of leek (Allium ampeloprasum L.) (J Microbiol Biotechnol Food Sci).

[820] Holgado F et al. In vitro fermentation of Allium by-products by gut bacteria 2021. Bioact Carbohydr Diet Fibre. 2021.

An in vitro study on the fermentation of Allium by-products by gut bacteria (Bioact Carbohydr Diet Fibre).

[821] Pérez-Burillo S et al. Effect of in vitro digestion-fermentation on Allium polyphenols 2018. Food Funct. 2018.

A study on the effect of in vitro digestion-fermentation on Allium polyphenols (Food Funct).

[822] EFSA NDA Panel. Scientific Opinion on dietary reference values for vitamin K2017. EFSA Journal. Link

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derives dietary reference values (DRVs) for vitamin K. In this Opinion, the Panel considers vitamin K to comprise both phylloquinone and menaquinones. The Panel considers that none of the biomarkers of vitamin K intake or status is suitable by itself to derive DRVs for vitamin K. Several health outcomes possibly associated with vitamin K intake were also considered but data could not be used to establish DRVs. The Panel considers that average requirements and population reference intakes for vitamin K cannot be derived for adults, infants and children, and therefore sets adequate intakes (AIs). The Panel considers that available evidence on occurrence, absorption, function and content in the body or organs of menaquinones is insufficient, and, therefore, sets AIs for phylloquinone only.

[823] Capitulare de villis vel curtis imperii (Charlemagne, ca. 800 AD).

Charlemagne's Capitulare de villis vel curtis imperii (ca. 800 AD), a historical primary source.

[824] Lanzotti V. The analysis of onion and garlic2006;1112(1-2):3–22. J Chromatogr A. Link

Onion (Allium cepa L.) and garlic (Allium sativum L.), among the oldest cultivated plants, are used both as a food and for medicinal applications. In fact, these common food plants are a rich source of several phytonutrients recognized as important elements of the Mediterranean diet, but are also used in the treatment and prevention of a number of diseases, including cancer, coronary heart disease, obesity, hypercholesterolemia, diabetes type 2, hypertension, cataract and disturbances of the gastrointestinal tract (e.g. colic pain, flatulent colic and dyspepsia). These activities are related to the thiosulfinates, volatile sulfur compounds, which are also responsible for the pungent of these vegetables. Besides these low-molecular weight compounds, onion and garlic are characterized by more polar compounds of phenolic and steroidal origin, often glycosilated, showing interesting pharmacological properties. These latter compounds, compared to the more studied thiosulfinates, present the advantages to be not pungent and more stable to cooking. Recently, there has been an increasing scientific attention on such compounds.

[825] . Diat L J.B. Lippincott, 1941. Cooking à la Ritz. 1941.

Louis Diat's cookbook Cooking à la Ritz (J.B. Lippincott, 1941), a culinary source.

[826] Fahey JW et al. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens1997;94(19):10367–10372. Proc Natl Acad Sci USA. Link

A study presenting broccoli sprouts as an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens (Proc Natl Acad Sci USA).

[827] Vermeulen M et al. Bioavailability and kinetics of sulforaphane in humans after consumption of cooked versus raw broccoli2008;56(22):10505–10509. J Agric Food Chem. Link

A human study on the bioavailability and kinetics of sulforaphane after consumption of cooked versus raw broccoli (J Agric Food Chem).

[828] Okunade O et al. Supplementation of the diet by exogenous myrosinase via mustard seeds to increase the bioavailability of sulforaphane in healthy human subjects after the consumption of cooked broccoli2018;62(18):e1700980. Mol Nutr Food Res. Link

A human study on supplementing the diet with exogenous myrosinase via mustard seeds to increase sulforaphane bioavailability after consumption of cooked broccoli (Mol Nutr Food Res).

[829] Yanaka A et al. Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and humans2009;2(4):353–360. Cancer Prev Res. Link

The isothiocyanate sulforaphane [SF; 1-isothiocyanato-4(R)-methylsulfinylbutane] is abundant in broccoli sprouts in the form of its glucosinolate precursor (glucoraphanin). SF is powerfully bactericidal against Helicobacter pylori infections, which are strongly associated with the worldwide pandemic of gastric cancer. Oral treatment with SF-rich broccoli sprouts of C57BL/6 female mice infected with H. pylori Sydney strain 1 and maintained on a high-salt (7.5\% NaCl) diet reduced gastric bacterial colonization, attenuated mucosal expression of tumor necrosis factor-alpha and interleukin-1beta, mitigated corpus inflammation, and prevented expression of high salt-induced gastric corpus atrophy. This therapeutic effect was not observed in mice in which the nrf2 gene was deleted, strongly implicating the important role of Nrf2-dependent antioxidant and anti-inflammatory proteins in SF-dependent protection. Forty-eight H. pylori-infected patients were randomly assigned to feeding of broccoli sprouts (70 g/d; containing 420 micromol of SF precursor) for 8 weeks or to consumption of an equal weight of alfalfa sprouts (not containing SF) as placebo. Intervention with broccoli sprouts, but not with placebo, decreased the levels of urease measured by the urea breath test and H. pylori stool antigen (both biomarkers of H. pylori colonization) and serum pepsinogens I and II (biomarkers of gastric inflammation).

[830] Kellingray L et al. Consumption of a diet rich in Brassica vegetables is associated with a reduced abundance of sulphate-reducing bacteria: a randomised crossover study2017;61(9):1600992. Mol Nutr Food Res. Link

Randomised crossover human study (Mol Nutr Food Res) reporting that a diet rich in Brassica vegetables is associated with reduced abundance of sulphate-reducing bacteria.

[831] Li F et al. Variation of glucoraphanin metabolism in vivo and ex vivo by human gut bacteria2011;106(3):408–416. Br J Nutr. Link

Glucosinolates, phytochemicals found in cruciferous vegetables, are metabolised to bioactive isothiocyanates (ITC) by certain bacteria in the human gut. Substantial individual variation in urinary ITC excretion has been observed in previous cruciferous vegetable-feeding studies. We hypothesised that individual differences in gut microbial community contribute to the observed variation in glucosinolate metabolism, i.e. gut microbiota composition between high- and low-ITC excreters differs. We recruited twenty-three healthy individuals and fed them a standardised meal containing 200 g of cooked broccoli. After the meal, 24 h urinary ITC excretion was measured. Study participants with the highest (n 5) and lowest (n 5) ITC excretion provided faecal samples for ex vivo bacterial cultivation with 50 μm-glucoraphanin, the major glucosinolate found in broccoli.

[832] Felker P et al. Concentrations of thiocyanate and goitrin in human plasma, their precursor concentrations in Brassica vegetables2016;74(4):248–258. Nutr Rev. Link

Brassica vegetables are common components of the diet and have beneficial as well as potentially adverse health effects. Following enzymatic breakdown, some glucosinolates in brassica vegetables produce sulforaphane, phenethyl, and indolylic isothiocyanates that possess anticarcinogenic activity. In contrast, progoitrin and indolylic glucosinolates degrade to goitrin and thiocyanate, respectively, and may decrease thyroid hormone production. Radioiodine uptake to the thyroid is inhibited by 194 μmol of goitrin, but not by 77 μmol of goitrin. Collards, Brussels sprouts, and some Russian kale (Brassica napus) contain sufficient goitrin to potentially decrease iodine uptake by the thyroid. However, turnip tops, commercial broccoli, broccoli rabe, and kale belonging to Brassica oleracae contain less than 10 μmol of goitrin per 100-g serving and can be considered of minimal risk.

[834] Verkerk R et al. Glucosinolates in Brassica vegetables: the influence of the food supply chain on intake, bioavailability and human health2009;53 Suppl 2:S219–S265. Mol Nutr Food Res. Link

Glucosinolates (GLSs) are found in Brassica vegetables. Examples of these sources include cabbage, Brussels sprouts, broccoli, cauliflower and various root vegetables (e.g. radish and turnip). A number of epidemiological studies have identified an inverse association between consumption of these vegetables and the risk of colon and rectal cancer. Animal studies have shown changes in enzyme activities and DNA damage resulting from consumption of Brassica vegetables or isothiocyanates, the breakdown products (BDP) of GLSs in the body. Mechanistic studies have begun to identify the ways in which the compounds may exert their protective action but the relevance of these studies to protective effects in the human alimentary tract is as yet unproven. In vitro studies with a number of specific isothiocyanates have suggested mechanisms that might be the basis of their chemoprotective effects.

[835] Bradlow HL et al. 2-hydroxyestrone: the 'good' estrogen1996;150 Suppl:S259–S265. J Endocrinol. Link

The issue of the role of 2-hydroxyestrone (2-OHE1) in breast cancer has been the subject of considerable controversy as to whether it is carcinogenic or anticarcinogenic. The expanding data base outlined below is most consistent with the conclusion that 2-OHE1 is anticarcinogenic. In every experimental model in which 2-hydroxylation was increased, protection against tumors was achieved. Correspondingly, when 2-hydroxylation was decreased, an increase in cancer risk was observed. Even more dramatically, in the case of laryngeal papillomas induction of 2-hydroxylation with indole-3-carbinol (I3C) has resulted in inhibition of tumor growth during the time that the patients continue to take 13C or vegetables rich in this compound.

[836] Reed GA et al. Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3'-diindolylmethane in healthy subjects2008;17(10):2619–2624. Cancer Epidemiol Biomarkers Prev. Link

We have completed a single ascending dose clinical study of the proposed chemopreventive agent 3,3'-diindolylmethane (DIM). The study agent was nutritional-grade, absorption-enhanced BioResponse 3,3'-diindolylmethane (BR-DIM). We determined the safety, tolerability, and pharmacokinetics of single doses of BR-DIM in drug-free, non-smoking, healthy men and women. Groups of four subjects were enrolled for each dose level. After randomization, one subject in each group received placebo whereas three received active BR-DIM. The doses administered were 50, 100, 150, 200, and 300 mg, with the 300-mg dose repeated in an additional group.

[838] Li F et al. Human gut bacterial communities are altered by addition of cruciferous vegetables to a controlled fruit- and vegetable-free diet2009;139(9):1685–1691. J Nutr. Link

In the human gut, commensal bacteria metabolize food components that typically serve as energy sources. These components have the potential to influence gut bacterial community composition. Cruciferous vegetables, such as broccoli and cabbage, contain distinctive compounds that can be utilized by gut bacteria. For example, glucosinolates can be hydrolyzed by certain bacteria, and dietary fibers can be fermented by a range of species. We hypothesized that cruciferous vegetable consumption would alter growth of certain bacteria, thereby altering bacterial community composition. We tested this hypothesis in a randomized, crossover, controlled feeding study.

[839] Volden J et al. Effect of thermal treatment on glucosinolates and antioxidant-related parameters in different cultivars of cauliflower2009;113:1100–1107. Food Chem. Link

A study on the effect of thermal treatment on glucosinolates and antioxidant-related parameters in different cauliflower cultivars (Food Chem).

[840] Picchi V et al. Phytochemical characterization of cauliflower (Brassica oleracea L. var. botrytis) byproducts 2020;9(4):451. Foods. 2020.

A phytochemical characterization of cauliflower (Brassica oleracea L. var. botrytis) by-products (Foods).

[842] Stahl W, Sies H. Lycopene: a biologically important carotenoid for humans?1996;336(1):1–9. Arch Biochem Biophys. 1996. Link

Lycopene is a carotenoid present in human blood (approximately 0.5 micromol/liter plasma), and the tissue levels vary from 1 nmol/g wet wt in adipose tissue to up to 20 nmol/g wet wt in adrenals and testes. Its biological activities include antioxidant activity (singlet oxygen quenching and peroxyl radical scavenging), induction of cell-cell communication, and growth control, but no provitamin A activity. Epidemiological studies suggest protective effects of lycopene on some types of cancer, e.g., prostate cancer. In vitro and in vivo studies on growth of tumor cells support this conclusion. The major sources of lycopene for the human are tomatoes and tomato products, and bioavailability from different food items varies considerably. Lycopene oxidation products have recently been identified in human serum.

[843] Gärtner C et al. Lycopene is more bioavailable from tomato paste than from fresh tomatoes1997;66(1):116–122. Am J Clin Nutr. Link

Lycopene bioavailability from a single dose of fresh tomatoes or tomato paste (23 mg lycopene) ingested together with 15 g corn oil was compared by analyzing carotenoid concentrations in the chylomicron fraction. The lycopene isomer pattern was the same in both fresh tomatoes and tomato paste. The triacylglycerol response in chylomicrons was not significantly different after both treatments. Ingestion of tomato paste was found to yield 2.5-fold higher total and all-trans-lycopene peak concentrations (P < 0.05 and P < 0.005, respectively) and 3.8-fold higher area under the curve (AUC) responses (P < 0.001) than ingestion of fresh tomatoes. The same was calculated for lycopene cis-isomers, but only the AUC response for the cis-isomers was significantly higher after ingestion of tomato paste (P < 0.005). No difference was observed in the alpha- and beta-carotene response.

[844] Fielding JM et al. Increases in plasma lycopene concentration after consumption of tomatoes cooked with olive oil2005;14(2):131–136. Asia Pac J Clin Nutr. Link

Lycopene is the main carotenoid in tomatoes and it has been hypothesised to be responsible for reducing the risk of some cancers and heart disease. The cooking of tomatoes with olive oil is a characteristic combination in the Southern Mediterranean diet. Previous studies have shown that the absorption of lycopene is greater from processed tomatoes than fresh tomatoes, since the processing breaks down the tomato cell matrix and makes the lycopene more available. The aim of the present study was to determine whether consumption of diced tomatoes cooked with olive oil resulted in higher plasma lycopene concentrations than consumption of diced tomatoes cooked without olive oil. Plasma lycopene concentrations were measured after 5 days on a low lycopene diet and again after a five-day dietary intervention, in healthy subjects, who consumed one meal per day of tomatoes (470 g) cooked with or without extra virgin olive oil (25 ml olive oil). There was an 82\% increase in plasma trans-lycopene (P< 0.001) and a 40\% in cis-lycopene (P = 0.002) concentrations in the 11 subjects who consumed tomatoes cooked in olive oil.

[845] Wiese M et al. Prebiotic effect of lycopene and dark chocolate on gut microbiome with systemic changes in liver metabolism, skeletal muscles and skin in moderately obese persons2019;2019:4625279. Biomed Res Int. 2019. Link

A study on the prebiotic effect of lycopene and dark chocolate on the gut microbiome, with systemic changes in liver, skeletal muscle and skin metabolism in moderately obese persons (Biomed Res Int).

[846] Story EN et al. An update on the health effects of tomato lycopene2010;1:189–210. Annu Rev Food Sci Technol. Link

A review updating the health effects of tomato lycopene (Annu Rev Food Sci Technol).

[847] Maiani G et al. Carotenoids: actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans 2009;53 Suppl 2:S194–S218. Mol Nutr Food Res. 2009.

A review of carotenoids covering food sources, intakes, stability, bioavailability and their protective role in humans (Mol Nutr Food Res).

[849] Maintz L, Novak N. Histamine and histamine intolerance2007;85(5):1185–1196. Am J Clin Nutr. Link

A review on histamine and histamine intolerance (Am J Clin Nutr).

[850] Webb AJ et al. Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite2008;51(3):784–790. Hypertension. Link

Diets rich in fruits and vegetables reduce blood pressure (BP) and the risk of adverse cardiovascular events. However, the mechanisms of this effect have not been elucidated. Certain vegetables possess a high nitrate content, and we hypothesized that this might represent a source of vasoprotective nitric oxide via bioactivation. In healthy volunteers, approximately 3 hours after ingestion of a dietary nitrate load (beetroot juice 500 mL), BP was substantially reduced (Delta(max) -10.4/8 mm Hg); an effect that correlated with peak increases in plasma nitrite concentration. The dietary nitrate load also prevented endothelial dysfunction induced by an acute ischemic insult in the human forearm and significantly attenuated ex vivo platelet aggregation in response to collagen and ADP. Interruption of the enterosalivary conversion of nitrate to nitrite (facilitated by bacterial anaerobes situated on the surface of the tongue) prevented the rise in plasma nitrite, blocked the decrease in BP, and abolished the inhibitory effects on platelet aggregation, confirming that these vasoprotective effects were attributable to the activity of nitrite converted from the ingested nitrate.

[851] Siervo M et al. Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis2013;143(6):818–826. J Nutr. Link

Diets including food products rich in inorganic nitrate are associated with lower blood pressure (BP). The evidence for the BP-lowering effects of inorganic nitrate and beetroot in randomized clinical trials has not been systematically assessed. The objective was to conduct a systematic review and meta-analysis of randomized clinical trials that examined the effects of inorganic nitrate and beetroot supplementation on BP. Medline, EMBASE, and Scopus databases were searched from inception to February 2013. The specific inclusion criteria were: 1) randomized clinical trials; 2) trials reporting effects on systolic or diastolic BP or both; and 3) trials comparing inorganic nitrate or beetroot juice supplementation with placebo control groups. Random-effects models were used to assess the pooled BP effect sizes.

[852] Lansley KE et al. Acute dietary nitrate supplementation improves cycling time trial performance2011;43(6):1125–1131. Med Sci Sports Exerc. Link

PURPOSE: Dietary nitrate supplementation has been shown to reduce the O2 cost of submaximal exercise and to improve high-intensity exercise tolerance. However, it is presently unknown whether it may enhance performance during simulated competition. The present study investigated the effects of acute dietary nitrate supplementation on power output (PO), VO2, and performance during 4- and 16.1-km cycling time trials (TT). METHODS: After familiarization, nine club-level competitive male cyclists were assigned in a randomized, crossover design to consume 0.5 L of beetroot juice (BR; containing ∼ 6.2 mmol of nitrate) or 0.5 L of nitrate-depleted BR (placebo, PL; containing ∼ 0.0047 mmol of nitrate), ∼ 2.5 h before the completion of a 4- and a 16.1-km TT. RESULTS: BR supplementation elevated plasma [nitrite] (PL = 241 ± 125 vs BR = 575 ± 199 nM, P < 0.05). The VO2 values during the TT were not significantly different between the BR and PL conditions at any elapsed distance (P > 0.05), but BR significantly increased mean PO during the 4-km (PL = 279 ± 51 vs BR = 292 ± 44 W, P < 0.05) and 16.1-km TT (PL = 233 ± 43 vs BR = 247 ± 44 W, P < 0.01).

[853] Govoni M et al. The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash2008;19(4):333–337. Nitric Oxide. Link

Recent studies surprisingly show that dietary inorganic nitrate, abundant in vegetables, can be metabolized in vivo to form nitrite and then bioactive nitric oxide. A reduction in blood pressure was recently noted in healthy volunteers after dietary supplementation with nitrate; an effect consistent with formation of vasodilatory nitric oxide. Oral bacteria have been suggested to play a role in bioactivation of nitrate by first reducing it to the more reactive anion nitrite. In a cross-over designed study in seven healthy volunteers we examined the effects of a commercially available chlorhexidine-containing antibacterial mouthwash on salivary and plasma levels of nitrite measured after an oral intake of sodium nitrate (10mg/kg dissolved in water). In the control situation the salivary and plasma levels of nitrate and nitrite increased greatly after the nitrate load. Rinsing the mouth with the antibacterial mouthwash prior to the nitrate load had no effect on nitrate accumulation in saliva or plasma but abolished its conversion to nitrite in saliva and markedly attenuated the rise in plasma nitrite.

[854] Clifford T et al. The potential benefits of red beetroot supplementation in health and disease2015;7(4):2801–2822. Nutrients. Link

Review article (Nutrients) on the potential health and disease benefits of red beetroot supplementation.

[855] Hobbs DA et al. Acute ingestion of beetroot bread increases endothelium-independent vasodilation and lowers diastolic blood pressure in healthy men2013;143(9):1399–1405. J Nutr. Link

A human study on how acute ingestion of beetroot bread increases endothelium-independent vasodilation and lowers diastolic blood pressure in healthy men (J Nutr).

[856] Holmes RP et al. Dietary oxalate and the risk for nephrolithiasis 2004;15(12):3225–3232. J Am Soc Nephrol. 2004.

A study on dietary oxalate and the risk for nephrolithiasis (J Am Soc Nephrol).

[858] Tang G. Bioconversion of dietary provitamin A carotenoids to vitamin A in humans2010;91(5):1468S–1473S. Am J Clin Nutr. Link

Recent progress in the measurement of the bioconversion of dietary provitamin A carotenoids to vitamin A is reviewed in this article. Methods to assess the bioavailability and bioconversion of provitamin A carotenoids have advanced significantly in the past 10 y, specifically through the use of stable isotope methodology, which includes the use of labeled plant foods. The effects of the food matrix on the bioconversion of provitamin A carotenoids to vitamin A, dietary fat effects, and the effect of genotype on the absorption and metabolism of beta-carotene have been reported recently. A summary of the major human studies that determined conversion factors for dietary beta-carotene to retinol is presented here, and these data show that the conversion efficiency of dietary beta-carotene to retinol is in the range of 3.6-28:1 by weight. There is a wide variation in conversion factors reported not only between different studies but also between individuals in a particular study. These findings show that the vitamin A value of individual plant foods rich in provitamin A carotenoids may vary significantly and need further investigation.

[859] Mortelé O et al. Consistent prebiotic effects of carrot RG-I on the gut microbiota of four human adult donors in the SHIME® model despite baseline individual variability2021;9(10):2109. Microorganisms. Link

In vitro study (Microorganisms) on the prebiotic effects of carrot RG-I on the gut microbiota of four human adult donors using the SHIME® model.

[860] Van den Abbeele P et al. A novel non-digestible, carrot-derived polysaccharide (cRG-I) selectively modulates the human gut microbiota while promoting gut barrier integrity2020;12(7):1917. Nutrients. 1917. Link

A study on a novel non-digestible, carrot-derived polysaccharide (cRG-I) that selectively modulates the human gut microbiota while promoting gut barrier integrity (Nutrients).

[861] Larsen LR et al. Polyacetylenes (falcarinol type) in vegetables 2019. J Agric Food Chem. 2019.

A study on polyacetylenes (falcarinol type) in vegetables (J Agric Food Chem).

[862] Brown L et al. Polyacetylenes from carrots and their potential health benefits 2020. Food Funct. 2020.

A study on polyacetylenes from carrots and their potential health benefits (Food Funct).

[863] Bode AM et al. Carotenoids and human health 2014. Adv Nutr. 2014.

A review on carotenoids and human health (Adv Nutr).

[864] Iorizzo M et al. A high-quality carrot genome assembly provides new insights into carotenoid accumulation and asterid genome evolution2016;48(6):657–666. Nat Genet. Link

A study presenting a high-quality carrot genome assembly that provides new insights into carotenoid accumulation and asterid genome evolution (Nat Genet).

[866] Barillari J et al. Sulforaphene and sulforaphane in the radish (Raphanus sativus L.) sprouts and seeds 2005;85(15):2587–2594. J Sci Food Agric. 2005.

A study on sulforaphene and sulforaphane in radish (Raphanus sativus L.) sprouts and seeds (J Sci Food Agric).

[867] Hanlon PR et al. Aqueous extract from the vegetative portion of Spanish black radish (Raphanus sativus L. var. niger) induces detoxification enzyme expression in HepG2 cells2009;1(4):356–365. J Funct Foods. Link

A study on how an aqueous extract from the vegetative portion of Spanish black radish (Raphanus sativus L. var. niger) induces detoxification enzyme expression in HepG2 cells (J Funct Foods).

[868] Yang X et al. Radish (Raphanus sativus) glucosinolates modulate gut microbiota and metabolome in mice 2024. Food Funct. 2024.

A mouse study on how radish (Raphanus sativus) glucosinolates modulate the gut microbiota and metabolome (Food Funct).

[869] Li F et al. Human gut bacterial communities are altered by addition of cruciferous vegetables to a controlled diet2009;139(9):1685–1691. J Nutr. Link

[870] Okunade O et al. Supplementation of the diet by exogenous myrosinase via mustard seeds increases sulforaphane bioavailability after cooked broccoli2018. Mol Nutr Food Res. Link

A human study on how supplementing the diet with exogenous myrosinase via mustard seeds increases sulforaphane bioavailability after cooked broccoli (Mol Nutr Food Res).

[871] Manchali S et al. Crucial facts about health benefits of popular cruciferous vegetables2012;4(1):94–106. J Funct Foods. Link

A review of crucial facts about the health benefits of popular cruciferous vegetables (J Funct Foods).

[872] Beevi SS et al. Polyphenolics profile, antioxidant and radical scavenging activity of leaves and stem of Raphanus sativus L2010;65(1):8–17. Plant Foods Hum Nutr. Link

Aerial parts (leaves and stem) of Raphanus sativus, which are usually discarded were found to possess potent antioxidant and radical scavenging activity, as measured by standard antioxidant assays. Methanolic and acetone extracts of R. sativus leaves had total polyphenolic content of 86.16 and 78.77 mg/g dry extract, which were comparable to the traditional rich sources such as green tea and black tea. HPLC identification of polyphenolics indicated the presence of catechin, protocatechuic acid, syringic acid, vanillic acid, ferulic acid, sinapic acid, o-coumaric acid, myricetin, and quercetin in leaves and stem. Among the different extraction solvents, methanolic extract of leaves and stem showed potent reductive capacity, significantly inhibited linoleic acid peroxidation and displayed metal chelating activity. Further, they scavenged free radicals effectively with IC50 (half maximal inhibitory concentration) of 31 and 42 microg/ml for DPPH radical, 23 and 52 microg/ml for superoxide radical, 67 and 197 microg/ml for hydrogen peroxide,and 56 and 62 microg/ml for nitric oxide, respectively. Leaves showed most potent antioxidant and radical scavenging activity as compared to stem, which may be accounted for the high polyphenolic content.

[874] Kellingray L et al. Consumption of a diet rich in Brassica vegetables is associated with a reduced abundance of sulphate-reducing bacteria — a randomised controlled trial2017;61(9):1600992. Mol Nutr Food Res. Link

Randomised controlled human trial (Mol Nutr Food Res) reporting that a diet rich in Brassica vegetables is associated with reduced abundance of sulphate-reducing bacteria.

[875] Roberfroid M. Inulin-type fructans: functional food ingredients2007;137(11 Suppl):2493S–2502S. J Nutr. Link

A food (ingredient) is regarded as functional if it is satisfactorily demonstrated to affect beneficially 1 or more target functions in the body beyond adequate nutritional effects. The term inulin-type fructans covers all beta(2<--1) linear fructans including native inulin (DP 2-60, DP(av) = 12), oligofructose (DP 2-8, DP(av) = 4), and inulin HP (DP 10-60, DP(av) = 25) as well as Synergy 1, a specific combination of oligofructose and inulin HP. Inulin-type fructans resist digestion and function as dietary fiber improving bowel habits. But, unlike most dietary fibers, their colonic fermentation is selective, thus causing significant changes in the composition of the gut microflora with increased and reduced numbers of potentially health-promoting bacteria and potentially harmful species, respectively. Both oligofructose and inulin act in this way and thus are prebiotic: they also induce changes in the colonic epithelium and in miscellaneous colonic functions. In particular, the claim "inulin-type fructans enhance calcium and magnesium absorption" is scientifically substantiated, and the most active product is oligofructose-enriched inulin (Synergy 1).

[876] EFSA NDA Panel. Scientific Opinion on the substantiation of a health claim related to "native chicory inulin" and maintenance of normal defecation2015;13(1):3951. EFSA Journal. Link

[877] Niness KR. Inulin and oligofructose: what are they?1999;129(7 Suppl):1402S–1406S. J Nutr. 1999. Link

A review explaining what inulin and oligofructose are (J Nutr).

[878] van Loo J et al. On the presence of inulin and oligofructose as natural ingredients in the western diet1995;35(6):525–552. Crit Rev Food Sci Nutr. Link

The classic definitions of inulin and oligofructose are constructively criticized. It is observed that inulin cannot unequivocally be described as a polydisperse 1-kestose-based (GFn) beta (2-->1) linear fructan chain, but that inulin always contains small amounts of Fm and branched molecules. This review article describes the presence of inulin and oligofructose in common foodstuffs. Historical data on human consumption add an extra dimension. Modern analytical techniques (HPLC, LGC, HPAEC-PAD) are used to check the variety of data mentioned in the literature throughout the past century. Methods to determine inulin and oligofructose in natural foodstuffs (cereals, fruit, and vegetables) are optimized and used to determine the loss of inulin during storage and during preparation of the food.

[879] Slavin J. Fiber and prebiotics: mechanisms and health benefits2013;5(4):1417–1435. Nutrients. Link

Review article in Nutrients on fiber and prebiotics, discussing their mechanisms of action and health benefits.

[880] Bouhnik Y et al. The capacity of nondigestible carbohydrates to stimulate fecal bifidobacteria in healthy humans: a double-blind, randomized, placebo-controlled, parallel-group, dose-response relation study2004;80(6):1658–1664. Am J Clin Nutr. Link

BACKGROUND: Nondigestible carbohydrates (NDCHs) are fermented in the colon, where they can selectively promote the growth of bifidobacteria. OBJECTIVE: Our aim was to determine the bifidogenic potential of different NDCHs used in human diets. DESIGN: Two hundred healthy volunteers participated in this double-blind study. During phase 1 (screening), 64 volunteers were randomly assigned to 8 groups of 8 subjects each; for 7 d, they ingested 10 g/d of 1 of the 7 NDCHs tested or of the placebo. During phase 2 (dose-response study), 136 volunteers were randomly assigned to 4 groups of 32 subjects who received 2.5, 5.0, 7.5, or 10 g/d, respectively (8 subjects/dose), of one of the NDCHs that were proven to be bifidogenic during phase 1 and a fifth group of 8 subjects (control subjects) who received the placebo. Stools were recovered before and after NDCH consumption.

[881] Carabin IG, Flamm WG. Evaluation of safety of inulin and oligofructose as dietary fiber1999;30(3):268–282. Regul Toxicol Pharmacol. Link

In the United States, most individuals consume far less dietary fiber than the daily value (DV) set at 25 g. The average daily consumption for inulin and oligofructose is estimated to be between 1 and 4 g in this country, with a higher intake of 3 to 11 g seen in Europe. Inulin and oligofructose are soluble, fermentable dietary fibers, of low net caloric value having many of the possible health benefits attributed to fiber. Such fiber consists of poly- and oligomers of fructose joined by beta(2-->1) fructosyl-fructose bonds. This class of fiber has been studied in a series of standard toxicological test systems. The studies have demonstrated that inulin-type fructans, when administered in the diet at high levels, do not result in mortality, morbidity, target organ toxicity, reproductive or developmental toxicity, or carcinogenicity.

[883] Sonia S et al. Effect of cooling of cooked white rice on resistant starch content and glycemic response2015;24(4):620–625. Asia Pac J Clin Nutr. Link

Cooling of cooked starch is known to cause starch retrogradation which increases resistant starch content. This study aimed to determine the effect of cooling of cooked white rice on resistant starch content and glycemic response in healthy subjects. Resistant starch contents were analyzed on freshly cooked white rice (control rice), cooked white rice cooled for 10 hours at room temperature (test rice I), and cooked white rice cooled for 24 hours at 4°C then reheated (test rice II). The results showed that resistant starch contents in control rice, test rice I, and test rice II were 0.64 g/100 g, 1.30 g/100 g, and 1.65 g/100 g, respectively. Test rice II had higher resistant starch content than test rice I, hence used in the clinical study along with control rice to characterize glycemic response in 15 healthy adults. The clinical study was a randomized, single-blind crossover study.

[884] Robertson MD et al. Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism2005;82(3):559–567. Am J Clin Nutr. Link

BACKGROUND: Resistant starch may modulate insulin sensitivity, although the precise mechanism of this action is unknown. OBJECTIVE: We studied the effects of resistant starch on insulin sensitivity and tissue metabolism. DESIGN: We used a 4-wk supplementation period with 30 g resistant starch/d, compared with placebo, in 10 healthy subjects and assessed the results by using arteriovenous difference methods. RESULTS: When assessed by euglycemic-hyperinsulinemic clamp, insulin sensitivity was higher after resistant starch supplementation than after placebo treatment (9.7 and 8.5 x 10(-2) mg glucose x kg(-1) x min(-1) x (mU insulin/L)(-1), respectively; P = 0.03); insulin sensitivity during the meal tolerance test (MTT) was 33\% higher (P = 0.05). Forearm muscle glucose clearance during the MTT was also higher after resistant starch supplementation (P = 0.03) despite lower insulin concentrations (P = 0.02); glucose clearance adjusted for insulin was 44\% higher. Subcutaneous abdominal adipose tissue nonesterified fatty acid (NEFA; P = 0.02) and glycerol (P = 0.05) release were lower with resistant starch supplementation, although systemic NEFA concentrations were not significantly altered.

[885] Wang Y et al. Resistant starch from potatoes improves stool frequency and consistency: a randomized controlled trial 2024. Sci Rep. 2024.

Randomized controlled trial (RCT) in Sci Rep examining the effect of potato-derived resistant starch on stool frequency and consistency.

[886] Bouchard J et al. Resistant starch type 3 (RS3) and the gut microbiome: a review 2022. Foods. 2022.

Review article in Foods on resistant starch type 3 (RS3) and its relationship with the gut microbiome.

[887] EFSA Panel on Contaminants in the Food Chain (CONTAM). Risks for human health related to the presence of glycoalkaloids in feed and food, in particular in potatoes and potato-derived products2020;18(8):e06222. EFSA Journal. Link

The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of glycoalkaloids (GAs) in feed and food. This risk assessment covers edible parts of potato plants and other food plants containing GAs, in particular, tomato and aubergine. In humans, acute toxic effects of potato GAs (α-solanine and α-chaconine) include gastrointestinal symptoms such as nausea, vomiting and diarrhoea. For these effects, the CONTAM Panel identified a lowest-observed-adverse-effect level of 1 mg total potato GAs/kg body weight (bw) per day as a reference point for the risk characterisation following acute exposure. In humans, no evidence of health problems associated with repeated or long-term intake of GAs via potatoes has been identified. No reference point for chronic exposure could be identified from the experimental animal studies.

[888] Mottram DS et al. Acrylamide is formed in the Maillard reaction2002;419(6906):448–449. Nature. Link

Nature paper reporting that acrylamide is formed during the Maillard reaction.

[889] Ostman EM et al. Vinegar dressing and cold storage of potatoes lowers postprandial glycaemic and insulinaemic responses in healthy subjects2005;59(9):983–988. Eur J Clin Nutr. Link

OBJECTIVE: To investigate the effects of cold storage and vinegar addition on glycaemic and insulinaemic responses to a potato meal in healthy subjects. SUBJECTS AND SETTING: A total of 13 healthy subjects volunteered for the study, and the tests were performed at Applied Nutrition and Food Chemistry, Lund University, Sweden. Experimental design and test meals:The study included four meals; freshly boiled potatoes, boiled and cold stored potatoes (8 degrees C, 24 h), boiled and cold stored potatoes (8 degrees C, 24 h) with addition of vinaigrette sauce (8 g olive oil and 28 g white vinegar (6\% acetic acid)) and white wheat bread as reference. All meals contained 50 g available carbohydrates and were served as a breakfast in random order after an overnight fast. Capillary blood samples were collected at time intervals during 120 min for analysis of blood glucose and serum insulin. Glycaemic (GI) and insulinaemic indices (II) were calculated from the incremental areas using white bread as reference.

[891] Hotz C et al. A large-scale intervention to introduce orange sweet potato in rural Mozambique increases vitamin A intakes among children and women2012;108(1):163–176. Br J Nutr. Link

β-Carotene-rich orange sweet potato (OSP) has been shown to improve vitamin A status of infants and young children in controlled efficacy trials and in a small-scale effectiveness study with intensive exposure to project inputs. However, the potential of this important food crop to reduce the risk of vitamin A deficiency in deficient populations will depend on the ability to distribute OSP vines and promote its household production and consumption on a large scale. In rural Mozambique, we conducted a randomised, controlled effectiveness study of a large-scale intervention to promote household-level OSP production and consumption using integrated agricultural, demand creation/behaviour change and marketing components. The following two intervention models were compared: a low-intensity (1 year) and a high-intensity (nearly 3 years) training model. The primary nutrition outcomes were OSP and vitamin A intakes by children 6-35 months and 3-5·5 years of age, and women. The intervention resulted in significant net increases in OSP intakes (model 1: 46, 48 and 97 g/d) and vitamin A intakes (model 1: 263, 254 and 492 μg retinol activity equivalents/d) among the younger children, older children and women, respectively.

[893] Sun H et al. Anthocyanins from purple sweet potato: composition, bioavailability, and health benefits 2019;8(11):528. Foods. 2019.

Review article in Foods on anthocyanins from purple sweet potato: their composition, bioavailability, and health benefits.

[894] Wang YJ et al. Acylated anthocyanins from purple sweet potato confer thermal and pH stability 2022. J Food Sci. 2022.

J Food Sci study on the thermal and pH stability conferred by acylated anthocyanins from purple sweet potato.

[895] Mohanraj R, Sivasankar S. Sweet potato (Ipomoea batatas [L.] Lam) — a valuable medicinal food: a review2014;17(7):733–741. J Med Food. Link

Review article in J Med Food on the sweet potato (Ipomoea batatas [L.] Lam) as a valuable medicinal food.

[896] Ji H et al. Purple sweet potato anthocyanins modulate gut microbiota: in vitro and in vivo evidence 2022. Food Funct. 2022.

Food Funct study examining, with in vitro and in vivo evidence, how purple sweet potato anthocyanins modulate the gut microbiota.

[897] Roullier C et al. Historical collections reveal patterns of diffusion of sweet potato in Oceania2013;110(6):2205–2210. PNAS. Link

PNAS study using historical collections to investigate the patterns of diffusion of sweet potato in Oceania.

[900] Cheney G. Rapid healing of peptic ulcers in patients receiving fresh cabbage juice1949;70(1):10–15. Calif Med. Link

Thirteen patients with peptic ulcer were treated with fresh cabbage juice, which, experiments have indicated, contains an antipeptic ulcer factor. This factor (vitamin U) prevents the development of histamin-induced peptic ulcers in guinea pigs. The average crater healing time for seven of these patients who had duodenal ulcer was only 10.4 days, while the average time as reported in the literature, in 62 patients treated by standard therapy, was 37 days. The average crater healing time for six patients with gastric ulcer treated with cabbage juice was only 7.3 days, compared with 42 days, as reported in the literature, for six patients treated by standard therapy. The rapid healing of peptic ulcers observed radiologically and gastroscopically in 13 patients treated with fresh cabbage juice indicates that the anti-peptic ulcer dietary factor may play an important role in the genesis of peptic ulcer in man.

[903] Hanschen FS et al. Reactivity and stability of glucosinolates and their breakdown products in foods2014;53(43):11430–11450. Angew Chem Int Ed Engl. Link

The chemistry of glucosinolates and their behavior during food processing is very complex. Their instability leads to the formation of a bunch of breakdown and reaction products that are very often reactive themselves. Although excessive consumption of cabbage varieties has been thought for long time to have adverse, especially goitrogenic effects, nowadays, epidemiologic studies provide data that there might be beneficial health effects as well. Especially Brassica vegetables, such as broccoli, radish, or cabbage, are rich in these interesting plant metabolites. However, information on the bioactivity of glucosinolates is only valuable when one knows which compounds are formed during processing and subsequent consumption. This review provides a comprehensive, in-depth overview on the chemical reactivity of different glucosinolates and breakdown products thereof during food preparation.

[904] Beganović J et al. Lactic acid bacteria in fermented vegetables: from selection to industrial application 2014. Front Microbiol. 2014.

Review article in Front Microbiol on lactic acid bacteria in fermented vegetables, from selection to industrial application.

[905] . Cook J , Hakluyt Society ed., 1955. The journals of Captain James Cook on his voyages of discovery. 1955.

Book edited by the Hakluyt Society (1955): the journals of Captain James Cook on his voyages of discovery.

[907] Siervo M et al. Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis. J Nutr 2013;143(6):818–826. . 2013. Link

[908] Chai W, Liebman M. Effect of different cooking methods on vegetable oxalate content. J Agric Food Chem 2005;53(8):3027–3030. . 2005. Link

J Agric Food Chem study on the effect of different cooking methods on the oxalate content of vegetables.

[909] Bondonno CP et al. Antibacterial mouthwash blunts oral nitrate reduction and increases blood pressure in treated hypertensive men. Am J Hypertens 2015;28(5):572–575. . 2015. Link

BACKGROUND: Endothelial nitric oxide (NO) is fundamental to cardiovascular health. Dietary nitrate and nitrate from endothelial derived NO metabolism provides a significant contribution to the circulating NO pool through the nitrate-nitrite-NO pathway. A critical step in this pathway is the reduction of nitrate to nitrite by the oral microbiota. We aimed to assess the effects of antibacterial mouthwash use on markers of nitrate-nitrite-NO metabolism and blood pressure in treated hypertensive men and women. METHODS: Fifteen treated hypertensive men and women (mean age 65 years) were recruited to a randomized controlled cross-over trial. The effects of 3-day use of antibacterial mouthwash on oral nitrate to nitrite reduction, salivary and plasma nitrate and nitrite, plasma cyclic guanosine monophosphate (cGMP) and systolic and diastolic blood pressure were compared to control (water).

[910] Sanchez-Echaniz J et al. Methemoglobinemia and consumption of vegetables in infants. Pediatrics 2001;107(5):1024–1028. . 2001. Link

OBJECTIVE: To assess clinical and epidemiologic data of 7 infants diagnosed with acquired methemoglobinemia at the pediatric emergency department between 1993 and 1998. All cases were attributed to the consumption of mixed vegetables. METHODS: Medical records were reviewed to collect anamnestic data; history of food ingestion; and results of physical examination, pulse oximetry, gasometry, cooximetry, urinalysis, and outcome. Local health authorities provided information on nitrate concentration in running water and in vegetables of common consumption in the area. RESULTS: The mean age of the patients was 8.14 months (range: 7-13). None of the infants was undernourished, had diarrhea, or was given any drug.

[911] Lidder S, Webb AJ. Vascular effects of dietary nitrate via the nitrate-nitrite-nitric oxide pathway. Br J Clin Pharmacol 2013;75(3):677–696. . 2013. Link

The discovery that dietary (inorganic) nitrate has important vascular effects came from the relatively recent realization of the 'nitrate-nitrite-nitric oxide (NO) pathway'. Dietary nitrate has been demonstrated to have a range of beneficial vascular effects, including reducing blood pressure, inhibiting platelet aggregation, preserving or improving endothelial dysfunction, enhancing exercise performance in healthy individuals and patients with peripheral arterial disease. Pre-clinical studies with nitrate or nitrite also show the potential to protect against ischaemia-reperfusion injury and reduce arterial stiffness, inflammation and intimal thickness. However, there is a need for good evidence for hard endpoints beyond epidemiological studies. Whilst these suggest reduction in cardiovascular risk with diets high in nitrate-rich vegetables (such as a Mediterranean diet), others have suggested possible small positive and negative associations with dietary nitrate and cancer, but these remain unproven. Interactions with other nutrients, such as vitamin C, polyphenols and fatty acids may enhance or inhibit these effects.

[912] EFSA Panel on Contaminants. Nitrate in vegetables — scientific opinion. EFSA Journal 2008;689:1–79. . 2008. Link

At the request of the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) performed a scientific risk assessment of nitrate in vegetables. The opinion reviews the sources of nitrate exposure and its possible health consequences, weighing the risks associated with nitrate intake against the beneficial effects of vegetable consumption. The document was published in the EFSA Journal (2008; 689:1-79).

[913] USDA FoodData Central. Spinach, raw — FDC ID 168462. Link

USDA FoodData Central database entry for raw spinach (FDC ID 168462).

[914] Hamblin TJ. Fake!1981;283(6307):1671–1674. BMJ. 1981. Link

Hamblin TJ's "Fake!" article published in the BMJ (1981).

[922] EFSA NDA Panel. Scientific Opinion on chicory inulin and maintenance of normal defecation2015;13(1):3951. EFSA Journal. Link

[925] Faris MA-IE et al. Lentils: nutritional value, health benefits and gut microbiota modulation2024. Nutrients. Link

This paper describes how lentils (Lens culinaris species) can positively affect health by reducing inflammation, providing antioxidants, and displaying antimicrobial properties. Lentils are rich in proteins, essential amino acids, minerals, and fibers, making them a valuable source of nutrition, particularly in low and middle-income countries. Lentils have many health benefits, including positive effects on diabetes management, support for cardiovascular health, and antioxidative properties. The antioxidative properties of lentils, attributed to their phenolic content, and their ability to inhibit inflammation-related enzymes are also discussed. We discuss the potential of lentils as a dietary tool in promoting immunity, reducing disease burdens, and preventing nutritional deficiencies. Overall, lentils are a highly nutritious food with various health benefits, including anti-inflammatory and antimicrobial effects.

[926] Mollard RC et al. The acute effects of a pulse-containing meal on glycaemic responses and measures of satiety2014;112(7):1117–1126. Br J Nutr. Link

Pulses are low glycaemic foods; however, their effect on satiation is unknown. The objective was to determine the effects of an ad libitum pulse meal on food intake (FI), appetite and blood glucose (BG) before and after a test meal (4 h later) and on FI at the test meal. Males (n 24, 22·8 kg/m2) received one of four treatments or control. The pulse treatments contained pasta and tomato sauce and 44 \% of energy from: (1) chickpeas, (2) lentils, (3) navy beans or (4) yellow peas. The control was pasta and tomato sauce (pasta and sauce). FI (satiation) was measured at the treatment meal (0-20 min) and at an ad libitum pizza meal 4 h later.

[927] Padhi EM, Ramdath DD. A review of the clinical evidence for cardiometabolic effects of pulses2017;9(11):1241. Nutrients. Link

Review article in Nutrients on the clinical evidence for the cardiometabolic effects of pulses.

[928] Johnson CR et al. The acute and longer-term effects of lentils on glucose metabolism2020;12(4):1110. Nutrients. Link

Lentils have potential to improve metabolic health but there are limited randomized clinical trials evaluating their comprehensive impact on metabolism. The aim of this study was to assess the impact of lentil-based vs. meat-based meals on fasting and postprandial measures of glucose and lipid metabolism and inflammation. Thirty-eight adults with an increased waist circumference (male ≥ 40 inches and female ≥ 35 inches) participated in a 12-week dietary intervention that included seven prepared midday meals totaling either 980 g (LEN) or 0 g (CON) of cooked green lentils per week. Linear models were used to assess changes in fasting and postprandial markers from pre- to post-intervention by meal group. Gastrointestinal (GI) symptoms were assessed through a survey randomly delivered once per week during the intervention. We found that regular consumption of lentils lowered fasting LDL (F = 5.53, p = 0.02) and total cholesterol levels (F = 8.64, p < 0.01) as well as postprandial glucose (β = -0.99, p = 0.01), IL-17 (β = -0.68, p = 0.04), and IL-1β (β = -0.70, p = 0.03) responses.

[929] Monk JM et al. Lentil consumption modulates gut microbiota composition in healthy adults 2024. Crit Rev Food Sci Nutr. 2024.

Crit Rev Food Sci Nutr study on how lentil consumption modulates gut microbiota composition in healthy adults.

[930] Costa GT et al. The role of pulse-based diets in microbiome-mediated metabolic improvements in prediabetes: an RCT2025. Nature Communications. Link

Randomized controlled trial (RCT) in Nature Communications on the role of pulse-based diets in microbiome-mediated metabolic improvements in prediabetes.

[931] Carbonero F et al. Resistant starch content of lentil varieties under different cooking and cooling regimens2023. Food Chemistry. Link

Food Chemistry study on the resistant starch content of lentil varieties under different cooking and cooling regimens.

[932] EFSA NDA Panel. Scientific opinion on dietary reference values for iron2015. EFSA Journal. Link

The EFSA NDA Panel derived Dietary Reference Values (DRVs) for iron, including the Average Requirement (AR) and Population Reference Intake (PRI). Predicted absorption values at a serum ferritin concentration of 30 µg/L (16% for men, 18% for women) were used to convert physiological requirements into dietary iron intakes. For adult men, median whole-body iron losses are 0.95 mg/day, the AR is 6 mg/day, and the PRI is 11 mg/day; the opinion describes the physiological role of iron in oxygen transport and energy metabolism.

[934] . Clemson Cooperative Extension 2022. Soaking and sprouting legumes: effects on RFOs. 2022.

Clemson Cooperative Extension publication (2022) on soaking and sprouting legumes and the effects on RFOs (raffinose-family oligosaccharides).

[935] Fernando WMU et al. Diets supplemented with chickpea or its main oligosaccharide component raffinose modify faecal microbial composition in healthy adults2010;106(8):1217–1224. Br J Nutr. Link

The effects of diets supplemented with either chickpea or its main oligosaccharide raffinose on the composition of the faecal microbial community were examined in 12 healthy adults (18-65 years) in a randomised crossover intervention study. Subjects consumed their usual diet supplemented with soups and desserts that were unfortified, or fortified with either 200 g/d of canned chickpeas or 5 g/d of raffinose for 3 week periods. Changes in faecal bacterial populations of subjects were examined using 16S rRNA-based terminal restriction fragment length polymorphisms (T-RFLP) and clone libraries generated from the diet pools. Classification of the clone libraries and T-RFLP analysis revealed that Faecalibacterium prausnitzii, reported to be an efficient butyrate producer and a highly metabolically active bacterium in the human intestinal microbiota, was more abundant in the raffinose diet and the chickpea diet compared to the control diet. However, no significant difference was observed in the faecal total short chain fatty acid concentration or in the levels of the components (butyrate, acetate and propionate) with the chickpea diet or the raffinose diet compared to the control diet. Bifidobacterium species were detected by T-RFLP in all three diet groups and quantitative real-time PCR (qPCR) analysis showed a marginal increase in 16S rRNA gene copies of Bifidobacterium with the raffinose diet compared to control (P>0.05).

[936] Wallace TC et al. The nutritional value and health benefits of chickpeas and hummus2016;8(12):766. Nutrients. Link

Review article (Nutrients) on the nutritional value and health benefits of chickpeas and hummus.

[937] Murty CM et al. Chickpea supplementation in an Australian diet affects food choice, satiety and bowel health2010;54(2):282–288. Appetite. Link

Appetite study on the effect of chickpea supplementation in an Australian diet on food choice, satiety, and bowel health.

[938] Singh B et al. Chickpea (Cicer arietinum L.) as a functional food: a comprehensive review 2024;11:1370450. Front Nutr. 2024.

Comprehensive review article in Front Nutr on chickpea (Cicer arietinum L.) as a functional food.

[939] EFSA NDA Panel. Scientific opinion on dietary reference values for protein2012. EFSA Journal. Link

The EFSA NDA Panel established Dietary Reference Values for protein, deriving the Population Reference Intake (PRI) from nitrogen balance studies. For healthy adults of both sexes, the Average Requirement (AR) is 0.66 g protein/kg body weight/day and the PRI is 0.83 g protein/kg body weight/day. Several health outcomes possibly associated with protein intake were also considered, but the data were insufficient to establish further DRVs.

[940] Costa GT et al. Pulse-based diets in microbiome-mediated metabolic improvements2025. Nature Communications. Link

Nature Communications study on pulse-based diets in microbiome-mediated metabolic improvements.

[941] Lazarte CE et al. Effect of cooking and cooling on resistant starch and in vitro digestibility of chickpea-based pasta2023;12(7):1442. Foods. Link

Foods study on the effect of cooking and cooling on the resistant starch and in vitro digestibility of chickpea-based pasta.

[943] Roy F et al. Bioactive proteins and peptides in pulse crops: nutritional, functional and cardiometabolic properties2010. Food Research International. Link

Food Research International study on bioactive proteins and peptides in pulse crops and their nutritional, functional, and cardiometabolic properties.

[944] Sonnante G, Hammer K, Pignone D. From the cradle of agriculture a handful of lentils: history of domestication2009;20(1):21–37. Rendiconti Lincei. Link

This review discusses the history of lentil (Lens culinaris) domestication, considering archaeobotanical, phylogenetic, and molecular evidence. The authors conclude that lentil domestication took place in the Near East, in the region known as the "cradle of agriculture". A wide range of morphological and molecular evidence supports Lens culinaris ssp. orientalis as the wild progenitor of the cultivated lentil.

[945] Zhang X et al. BE GONE: bean-based feasibility randomized clinical trial in obese individuals at risk for colorectal neoplasia2023. eClinicalMedicine. Link

"BE GONE" bean-based feasibility randomized clinical trial in eClinicalMedicine, conducted in obese individuals at risk for colorectal neoplasia.

[946] Hill EB et al. A legume-enriched diet improves metabolic health in prediabetes mediated through gut microbiome: a randomized controlled trial2025;16:56084. Nat Commun. Link

Randomized controlled trial (RCT) in Nat Commun showing that a legume-enriched diet improves metabolic health in prediabetes mediated through the gut microbiome.

[947] Bessada SMF et al. Pulses and food security: dietary protein, digestibility, bioactive and functional properties2019. Trends Food Sci Technol. Link

Trends Food Sci Technol article on pulses and food security, covering their dietary protein, digestibility, bioactive, and functional properties.

[948] Ganesan K, Xu B. Polyphenol-rich dry common beans (Phaseolus vulgaris L.) and their health benefits2017;18(11):2331. Int J Mol Sci. Link

Review article in Int J Mol Sci on polyphenol-rich dry common beans (Phaseolus vulgaris L.) and their health benefits.

[949] Tan SY et al. Beans and health: a review of clinical trials 2024. Crit Rev Food Sci Nutr. 2024.

Review article in Crit Rev Food Sci Nutr surveying clinical trials on beans and health.

[950] Birt DF et al. Resistant starch: promise for improving human health2013;4(6):587–601. Adv Nutr. Link

Review article in Adv Nutr on resistant starch and its promise for improving human health.

[951] Bento APN et al. Resistant starch and gut microbiota interactions: a current review of pulses 2024;13(4):506. Foods. 2024.

Current review in Foods on resistant starch and gut microbiota interactions in the context of pulses.

[952] . U.S. Food and Drug AdministrationFDA Foodborne Pathogenic Microorganisms 2nd Edition. Bad Bug Book: Phytohaemagglutinin. Link

Chapter on phytohaemagglutinin from the U.S. FDA "Bad Bug Book" (Foodborne Pathogenic Microorganisms, 2nd Edition).

[954] Bitocchi E, Nanni L et al. Mesoamerican origin of the common bean (Phaseolus vulgaris L.) is revealed by sequence data2012;109(14):E788–E796. Proc Natl Acad Sci USA. Link

Proc Natl Acad Sci USA study revealing the Mesoamerican origin of the common bean (Phaseolus vulgaris L.) through sequence data.

[955] Dahl WJ et al. Effects of pea hull fiber on bowel function in elderly people2003. Br J Nutr. Link

Dietary fiber fortification of food offers a preventative strategy that is a less invasive alternative to laxatives and enemas in the management of constipation in elderly individuals. To determine if a moderate increase in fiber provided in foods would increase bowel movement frequency among elderly institutionalized residents, data were collected on the same elderly residents (n=114) before and during a 6-week intervention. The intervention consisted of adding finely processed pea hull fiber (1-3 g/serving) to 3 to 4 foods each day. Laxative and enema use was monitored. Mean number of bowel movements/month increased from 18.7+/-9.4 to 20.1+/-9.6 (n=114, P=.034), and in 17 residents with low baseline frequency, the increase was highly significant (8.8+/-1.0 to 12.6+/-3.8 bowel movements/month, P=.001). With treatment, prune-based laxative administration decreased (P<.001).

[956] Lambert JE et al. Consuming yellow pea fiber reduces voluntary energy intake: a randomized trial2017. Nutrients. Link

BACKGROUND \& AIMS: The purpose of this randomized, double-blind, placebo-controlled study was to assess the effects of yellow pea fiber intake on body composition and metabolic markers in overweight/obese adults. METHODS: Participants (9 M/41 F; age 44 ± 15 y, BMI 32.9 ± 5.9 kg/m2) received isocaloric doses of placebo (PL) or pea fiber (PF; 15 g/d) wafers for 12 weeks. Outcome measures included changes in anthropometrics, body composition (DXA), oral glucose tolerance test (OGTT), food intake (ad libitum lunch buffet), and biochemical indices. RESULTS: The PF group lost 0.87 ± 0.37 kg of body weight, primarily due to body fat (-0.74 ± 0.26 kg), whereas PL subjects gained 0.40 ± 0.39 kg of weight over the 12 weeks (P = 0.022). The PF group consumed 16\% less energy at the follow-up lunch buffet (P = 0.026), whereas the PL group did not change. During the OGTT, glucose area under the curve (AUC) was lower in PF subjects at follow-up (P = 0.029); insulin increased in both groups over time (P = 0.008), but more so in the PL group (38\% higher AUC vs. 10\% higher in the PF group).

[957] Tosh SM, Yada S. Dietary fibres in pulse seeds and fractions: characterization, functional attributes, and applications2010. Food Res Int. Link

Food Res Int study on dietary fibres in pulse seeds and fractions: their characterization, functional attributes, and applications.

[958] Vidal-Valverde C et al. Galacto-oligosaccharides and effects on gut microbiota in pea-based diets 2019. J Sci Food Agric. 2019.

J Sci Food Agric study on galacto-oligosaccharides and their effects on gut microbiota in pea-based diets.

[959] Marinangeli CPF et al. The effect of pulse-based pasta on gut microbiota composition: a randomized pilot 2023. Frontiers in Nutrition. 2023.

Randomized pilot trial in Frontiers in Nutrition on the effect of pulse-based pasta on gut microbiota composition.

[960] Petropoulou K et al. A high-protein high-fibre breakfast promotes ileal appetite-relevant peptide release and modulates short-chain fatty acid production 2024;131(8):1346–1358. Br J Nutr. 2024.

Br J Nutr study showing that a high-protein high-fibre breakfast promotes ileal appetite-relevant peptide release and modulates short-chain fatty acid production.

[961] EFSA NDA Panel. Scientific opinion on dietary fibre2010. EFSA Journal. Link

The EFSA NDA Panel established Dietary Reference Values for carbohydrates and dietary fibre. In this opinion, dietary fibre is defined as non-digestible carbohydrates plus lignin. The Panel proposes a reference intake range of 45-60 E% for carbohydrates (for adults and children older than one year) and sets the fibre requirement at 25 g/day.

[963] Pavanello A et al. Pea hull fibre as a functional food ingredient: technological and clinical perspectives 2022. Trends Food Sci Technol. 2022.

Trends Food Sci Technol article on pea hull fibre as a functional food ingredient, from technological and clinical perspectives.

[964] Smýkal P et al. The role of the testa during development and in establishment of dormancy of the legume seed2014;5:351. Front Plant Sci. Link

Front Plant Sci study on the role of the testa during development and in the establishment of dormancy of the legume seed.

[965] Smith SC et al. The effect of lupin kernel fibre on faecal microbial activity and bowel function in healthy adults2006;45(4):205–212. Eur J Nutr. Link

BACKGROUND: Changes in the composition of gastrointestinal microbiota by dietary interventions using pro- and prebiotics provide opportunity for improving health and preventing disease. However, the capacity of lupin kernel fiber (LKFibre), a novel legume-derived food ingredient, to act as a prebiotic and modulate the colonic microbiota in humans needed investigation. AIM OF THE STUDY: The present study aimed to determine the effect of LKFibre on human intestinal microbiota by quantitative fluorescent in situ hybridization (FISH) analysis. DESIGN: A total of 18 free-living healthy males between the ages of 24 and 64 years consumed a control diet and a LKFibre diet (containing an additional 17-30 g/day fiber beyond that of the control-incorporated into daily food items) for 28 days with a 28-day washout period in a single-blind, randomized, crossover dietary intervention design. METHODS: Fecal samples were collected for 3 days towards the end of each diet and microbial populations analyzed by FISH analysis using 16S rRNA gene-based oligonucleotide probes targeting total and predominant microbial populations. RESULTS: Significantly higher levels of Bifidobacterium spp. (P = 0.001) and significantly lower levels of the clostridia group of C. ramosum, C. spiroforme and C. cocleatum (P = 0.039) were observed on the LKFibre diet compared with the control.

[966] Fechner A, Kiehntopf M, Jahreis G. The formation of short-chain fatty acids is positively associated with the blood lipid-lowering effect of lupin kernel fiber in moderately hypercholesterolemic adults2014;144(2):134–140. J Nutr. Link

Lupin kernel fiber beneficially modifies blood lipids because of its bile acid-binding capacity. The aim of this study was to evaluate the preventive effects of a lupin kernel fiber preparation on cardiovascular diseases and to clarify possible mechanisms. In a randomized, double-blind, controlled crossover trial, 60 moderately hypercholesterolemic adults (plasma total cholesterol: >5.2 mmol/L) passed 3 intervention periods in different orders with a 2-wk washout phase between each. Participants consumed either a high-fiber diet containing 25-g/d lupin kernel fiber (LF) or citrus fiber (CF), or a low-fiber control diet (CD) for 4 wk each. Anthropometric, plasma, and fecal variables were assessed at baseline and after the interventions. Contrary to the CF period, total (9\%) and LDL (12\%) cholesterol as well as triacylglycerols (10\%) were lower after the LF period when compared with the CD period [P ≤ 0.02, adjusted for baseline, age, gender, and body mass index (BMI)].

[967] Belski R et al. Effects of lupin-enriched foods on body composition and cardiovascular disease risk factors: an RCT2011. Int J Obes. Link

Randomized controlled trial (RCT) in Int J Obes on the effects of lupin-enriched foods on body composition and cardiovascular disease risk factors.

[968] Lee YP et al. Effects of lupin kernel flour-enriched bread on blood pressure: a controlled trial2009;89(3):766–772. Am J Clin Nutr. Link

Controlled trial in Am J Clin Nutr on the effects of lupin kernel flour-enriched bread on blood pressure.

[969] Hall RS et al. Lupin kernel fibre-enriched foods beneficially modify serum lipids: a randomized trial2005;59(3):325–333. Eur J Clin Nutr. Link

OBJECTIVE: To examine the effect of a diet containing a novel legume food ingredient, Australian sweet lupin (Lupinus angustifolius) kernel fibre (LKFibre), compared to a control diet without the addition of LKFibre, on serum lipids in men. DESIGN: Randomized crossover dietary intervention study. SETTING: Melbourne, Australia--Free-living men. SUBJECTS: A total of 38 healthy males between the ages of 24 and 64 y completed the intervention. INTERVENTION: Subjects consumed an LKFibre and a control diet for 1 month each. Both diets had the same background menus with seven additional experimental foods that either contained LKFibre or did not.

[970] Lambert C et al. Lupin kernel fibre as functional food ingredient: nutritional and technological perspectives2022;14(9):1873. Nutrients. Link

Nutrients article on lupin kernel fibre as a functional food ingredient, from nutritional and technological perspectives.

[971] EFSA NDA Panel. Scientific opinion on the safety of sweet lupin protein as a novel food 2014. EFSA Journal. 2014.

EFSA NDA Panel scientific opinion (2014) on the safety of sweet lupin protein as a novel food.

[972] Goggin DE et al. Quinolizidine alkaloid composition of Australian sweet and bitter lupin varieties 2013. J Agric Food Chem. 2013.

J Agric Food Chem study on the quinolizidine alkaloid composition of Australian sweet and bitter lupin varieties.

[973] AAAAI. Lupin allergy and peanut cross-reactivity. American Academy of Allergy, Asthma & Immunology 2023. . 2023.

American Academy of Allergy, Asthma & Immunology (AAAAI) resource (2023) on lupin allergy and peanut cross-reactivity.

[975] Holscher HD et al. Walnut consumption alters the gastrointestinal microbiota, microbially derived secondary bile acids, and health markers in healthy adults: a randomized controlled trial2018;148(6):861–867. J Nutr. Link

Randomized controlled trial (RCT) in J Nutr on how walnut consumption alters the gastrointestinal microbiota, microbially derived secondary bile acids, and health markers in healthy adults.

[976] Bamberger C et al. A walnut-enriched diet affects gut microbiome in healthy Caucasian subjects: a randomized, controlled trial2018;10(2):244. Nutrients. Link

Randomized controlled trial (RCT) in Nutrients on how a walnut-enriched diet affects the gut microbiome in healthy Caucasian subjects.

[977] Sala-Vila A et al. Effect of a 2-year diet intervention with walnuts on cognitive decline: the Walnuts and Healthy Aging (WAHA) Study2020;111(3):590–600. Am J Clin Nutr. Link

Am J Clin Nutr study from the Walnuts and Healthy Aging (WAHA) Study, examining the effect of a 2-year diet intervention with walnuts on cognitive decline.

[978] Andreux PA et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans2019;1:595–603. Nat Metab. Link

Nat Metab study on the mitophagy activator urolithin A, its safety, and the molecular signature of improved mitochondrial and cellular health it induces in humans.

[979] Tomás-Barberán FA et al. Urolithins, the rescue of "old" metabolites to understand a "new" concept: metabotypes as a nexus among diet, microbiota, and health2017;61(1). Mol Nutr Food Res. Link

Urolithins are dibenzo[b,d]pyran-6-one derivatives that are produced by the human gut microbiota from ellagitannins and ellagic acid (EA). These metabolites are much better absorbed than their precursors and have been suggested to be responsible for the health effects attributed to ellagitannins and EA that occur in food products as berries and nuts. In the present review, the role and potential of urolithins in human health are critically reviewed, and a perspective of the research approach needed to demonstrate these health effects is presented, based on the existing knowledge. The analytical methods available for urolithin analysis, their occurrence in different tissues and biological fluids, and their metabolism by human gut microbiota are considered. In addition, the interindividual variability observed for the production of urolithins (metabotypes) and its relationship with health status and dysbiosis are also reviewed. The potential mechanisms of action of urolithins are also critically discussed, paying attention to the concentration and the type of metabolites used in the in vitro and in vivo assays and the physiological significance of the results obtained.

[980] Reiter RJ et al. Melatonin in walnuts: influence on levels of melatonin and total antioxidant capacity of blood2005;21(9):920–924. Nutrition. Link

Nutrition study on melatonin in walnuts and its influence on blood melatonin levels and total antioxidant capacity.

[981] Bolling BW et al. Tree nut phytochemicals: composition, antioxidant capacity, bioactivity, impact factors2011;24(2):244–275. Nutr Res Rev. Link

Tree nuts contain an array of phytochemicals including carotenoids, phenolic acids, phytosterols and polyphenolic compounds such as flavonoids, proanthocyanidins (PAC) and stilbenes, all of which are included in nutrient databases, as well as phytates, sphingolipids, alkylphenols and lignans, which are not. The phytochemical content of tree nuts can vary considerably by nut type, genotype, pre- and post-harvest conditions, as well as storage conditions. Genotype affects phenolic acids, flavonoids, stilbenes and phytosterols, but data are lacking for many other phytochemical classes. During the roasting process, tree nut isoflavones, flavanols and flavonols were found to be more resistant to heat than the anthocyanins, PAC and trans-resveratrol. The choice of solvents used for extracting polyphenols and phytosterols significantly affects their quantification, and studies validating these methods for tree nut phytochemicals are lacking. The phytochemicals found in tree nuts have been associated with antioxidant, anti-inflammatory, anti-proliferative, antiviral, chemopreventive and hypocholesterolaemic actions, all of which are known to affect the initiation and progression of several pathogenic processes.

[983] FDA. Qualified health claims: letter of enforcement discretion — nuts and coronary heart disease, 2003. Docket No. 02P-0505. 2003. Link

An FDA letter of enforcement discretion (Docket No. 02P-0505) permitting a qualified health claim about nuts and coronary heart disease.

[984] Mandalari G et al. Bioaccessibility of macronutrients in almonds: implications for nutrition 2008;100(2):282–289. Br J Nutr. 2008.

A Br J Nutr article on the bioaccessibility of macronutrients in almonds and its nutritional implications.

[985] Liu Z et al. Prebiotic effects of almonds and almond skins on intestinal microbiota in healthy adult humans2014;26:1–6. Anaerobe. Link

A human study (Anaerobe) examining the prebiotic effects of almonds and almond skins on the intestinal microbiota in healthy adults.

[986] Burns AM et al. Diet quality improves for parents and children when almonds are incorporated into their daily diet 2016;36(1):80–89. Nutr Res. 2016. Link

A randomized crossover study evaluated how incorporating almonds into the daily diet affects diet quality in parents and their children. Participants consumed almonds and/or almond butter daily for three weeks (parents ~1.5 oz/day, children ~0.5 oz/day) as part of their usual diet, with a 6-week washout and an almond-free control period. Almond intake improved overall diet quality by displacing empty calories, and almonds were well-liked by both adults and children.

[987] Holscher HD et al. Almond consumption and processing affects the composition of the gastrointestinal microbiota of healthy adults: a randomized controlled trial2018;10(2):126. Nutrients. Link

Randomized controlled human trial (Nutrients) examining how almond consumption and processing affect the gastrointestinal microbiota composition of healthy adults.

[988] Musa-Veloso K et al. The effects of almond consumption on fasting blood lipid levels: a systematic review and meta-analysis of randomised controlled trials2016;5:e34. J Nutr Sci. Link

Systematic review and meta-analysis of randomised controlled trials (J Nutr Sci) on the effects of almond consumption on fasting blood lipid levels.

[989] Berryman CE et al. Effects of daily almond consumption on cardiometabolic risk and abdominal adiposity in healthy adults with elevated LDL-cholesterol: a randomized controlled trial2015;4(1):e000993. J Am Heart Assoc. Link

A randomized controlled trial (J Am Heart Assoc) on the effects of daily almond consumption on cardiometabolic risk and abdominal adiposity in healthy adults with elevated LDL-cholesterol.

[991] Ukhanova M et al. Effects of almond and pistachio consumption on gut microbiota composition in a randomised cross-over human feeding study2014;111(12):2146–2152. Br J Nutr. Link

A randomized cross-over human feeding study (Br J Nutr) on the effects of almond and pistachio consumption on gut microbiota composition.

[992] Liu AG, Ford NA, Hu FB, Zelman KM, Mozaffarian D, Kris-Etherton PM. A healthy approach to dietary fats: understanding the science and taking action to reduce consumer confusion 2017;16(1):53. Nutr J. 2017.

A Nutr J article on a science-based approach to dietary fats and actions to reduce consumer confusion.

[993] Hernández-Alonso P et al. Beneficial effect of pistachio consumption on glucose metabolism, insulin resistance, inflammation, and related metabolic risk markers: a randomized clinical trial2014;37(11):3098–3105. Diabetes Care. Link

A randomized clinical trial (Diabetes Care) on the effect of pistachio consumption on glucose metabolism, insulin resistance, inflammation and related metabolic risk markers.

[994] Bulló M et al. Nutrition attributes and health effects of pistachio nuts2015;113(S2):S79–S93. Br J Nutr. Link

A review article (Br J Nutr) on the nutritional attributes and health effects of pistachio nuts.

[995] Mandalari G et al. Pistachios as a potential source of carotenoids: a review 2020. Int J Food Sci Nutr. 2020.

A review article (Int J Food Sci Nutr) on pistachios as a potential source of carotenoids.

[996] Painter JE et al. The use of pistachio shells as a visual cue to reduce caloric intake 2011;57(2):418–420. Appetite. 2011. Link

This study examined whether leaving consumed pistachio shells in view as a visual cue reduces caloric intake. Among faculty and staff at a university (n=118), shells were either left in the bowl until the end of the day or removed every two hours; with shells visible, participants consumed fewer calories on average (about 216 vs. 264 calories). The authors conclude that leaving pistachio shells as a visual cue of consumption may help people eat fewer calories.

[997] Sankaranarayanan R et al. Nuts and the gut microbiome: a systematic review of randomized controlled trials 2022. Adv Nutr. 2022.

A systematic review of randomized controlled trials (Adv Nutr) on nuts and the gut microbiome.

[999] Pelvan E, Olgun EO, Karadağ A, Alasalvar C. Phenolic profiles and antioxidant activity of Turkish Tombul hazelnut samples (natural, roasted, and roasted hazelnut skin)2018;244:102–108. Food Chem. 2018. Link

The phenolic profiles and antioxidant status of hazelnut samples [natural (raw) hazelnut, roasted hazelnut, and roasted hazelnut skin] were compared. Free and bound (ester-linked and glycoside-linked) phenolic acids were examined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Comprehensive identification of phenolics was carried out using Q-exactive hybrid quadrupole-orbitrap mass spectrometer (Q-OT-MS). Samples were also assessed for their total phenolics and antioxidant activities using three different assays. Ten free and bound phenolic acids were quantified in hazelnut samples. Roasted hazelnut skin contained the highest content of total phenolic acids, followed by natural and roasted hazelnuts.

[1000] Tey SL et al. Long-term consumption of high energy-dense snack foods on sensory-specific satiety and intake 2013;109(2):320–328. Br J Nutr. 2013.

A Br J Nutr article on the effect of long-term consumption of high energy-dense snack foods on sensory-specific satiety and intake.

[1001] Perna S et al. Effect of hazelnut consumption on blood lipids and body weight: a systematic review and Bayesian meta-analysis2016;8(12):747. Nutrients. Link

Hazelnuts are rich in monounsaturated fatty acids and antioxidant bioactive substances: their consumption has been associated with a decreased risk of cardiovascular disease events. A systematic review and a meta-analysis was performed to combine the results from several trials and to estimate the pooled (overall) effect of hazelnuts on blood lipids and body weight outcomes. Specifically, a Bayesian random effect meta-analysis of mean differences of Δ-changes from baseline across treatment (MDΔ) (i.e., hazelnut-enriched diet vs. control diet) has been conducted. Nine studies representing 425 participants were included in the analysis. The intervention diet lasted 28-84 days with a dosage of hazelnuts ranging from 29 to 69 g/day. Out of nine studies, three randomized studies have been meta-analyzed showing a significant reduction in low-density lipoprotein (LDL) cholesterol (pooled MDΔ = -0.150 mmol/L; 95\% highest posterior density interval (95\%HPD) = -0.308; -0.003) in favor of a hazelnut-enriched diet.

[1002] Liccardo D et al. Pediatric NAFLD and hazelnut: an 8-week pilot trial 2019. Children. 2019.

An 8-week pilot trial (Children) on hazelnut in pediatric NAFLD (non-alcoholic fatty liver disease).

[1003] Di Renzo L et al. Hazelnut and the gut: an in vitro and in vivo study 2017. Frontiers in Microbiology. 2017.

An in vitro and in vivo study (Frontiers in Microbiology) on hazelnut and the gut.

[1004] Mistry HD et al. Hazelnut skin extract: a source of natural antioxidants 2021. Food Chemistry. 2021.

A Food Chemistry article on hazelnut skin extract as a source of natural antioxidants.

[1005] Sankaranarayanan R et al. Nuts and the gut microbiome: a systematic review of RCTs 2022. Adv Nutr. 2022.

A systematic review of RCTs (Adv Nutr) on nuts and the gut microbiome.

[1007] Du Toit G et al. Randomized trial of peanut consumption in infants at risk for peanut allergy2015;372(9):803–813. (LEAP study). N Engl J Med. Link

A randomized trial (N Engl J Med, LEAP study) of peanut consumption in infants at risk for peanut allergy.

[1008] Du Toit G et al. Effect of avoidance on peanut allergy after early peanut consumption2016;374(15):1435–1443. (LEAP-On). N Engl J Med. Link

An N Engl J Med article (LEAP-On) on the effect of avoidance on peanut allergy after early peanut consumption.

[1009] NIAID. Addendum guidelines for the prevention of peanut allergy in the United States 2017;139(1):29–44. J Allergy Clin Immunol. 2017.

A NIAID addendum guideline (J Allergy Clin Immunol) for the prevention of peanut allergy in the United States.

[1010] Parilli-Moser I et al. Consumption of peanut products modulates gut microbiota composition and short-chain fatty acid production in adults: a randomized clinical trial 2021. Clin Nutr. 2021.

A randomized clinical trial (Clin Nutr) on how peanut product consumption modulates gut microbiota composition and short-chain fatty acid production in adults.

[1011] Luu HN et al. Prospective evaluation of the association of nut/peanut consumption with total and cause-specific mortality 2015;175(5):755–766. JAMA Intern Med. 2015.

A prospective study (JAMA Intern Med) evaluating the association of nut/peanut consumption with total and cause-specific mortality.

[1012] Toomer OT. A comprehensive review of the value-added uses of peanut (Arachis hypogaea) skins and by-products 2020. Crit Rev Food Sci Nutr. 2020. Link

This review summarizes the value-added uses of peanut (Arachis hypogaea) skins and by-products. Globally, peanuts are grown mainly for oil, peanut butter, confections, and snacks, leaving by-products (skins, hulls) typically discarded as waste. The author identifies peanut skins and their extracts as having value-added attributes as an antioxidant, functional food ingredient, animal feed ingredient, and antimicrobial agent.

[1013] Bonku R, Yu J. Health aspects of peanuts as an outcome of its chemical composition 2020. Food Sci Hum Wellness. 2020.

A Food Sci Hum Wellness article on the health aspects of peanuts as an outcome of their chemical composition.

[1015] Vuksan V et al. Reduction in postprandial glucose excursion and prolongation of satiety: possible explanation of the long-term effects of whole grain Salba (Salvia hispanica L.)2010;64(4):436–438. Eur J Clin Nutr. 2010. Link

A Eur J Clin Nutr article on whole grain Salba (Salvia hispanica L.) and postprandial glucose excursion and satiety.

[1016] Vuksan V et al. Salba-chia (Salvia hispanica L.) in the treatment of overweight and obese patients with type 2 diabetes: a double-blind randomized controlled trial2017;27(2):138–146. Nutr Metab Cardiovasc Dis. Link

A double-blind randomized controlled trial (Nutr Metab Cardiovasc Dis) of Salba-chia (Salvia hispanica L.) in overweight and obese patients with type 2 diabetes.

[1017] Nieman DC et al. Chia seed supplementation and disease risk factors in overweight women: a metabolomics investigation 2012;18(7):700–708. J Altern Complement Med. 2012. Link

A double-blind, randomized, placebo-controlled study used a metabolomics approach to assess the effects of milled and whole chia seed on disease risk factors in overweight postmenopausal women. Sixty-two overweight (BMI ≥25), nonsmoking, postmenopausal women (aged 49-75) consumed 25 g/day of chia seed (whole or milled) or placebo (poppy seed) for 10 weeks. Milled chia seed at 25 g/day increased plasma ALA and EPA but had no effect on inflammation or disease risk factors by either traditional or metabolomics-based measures.

[1018] EFSA Panel on Dietetic Products Nutrition, Allergies. Scientific Opinion on the substantiation of health claims related to ALA 2009;7(9):1252. EFSA Journal. 2009.

A Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (EFSA Journal) on the substantiation of health claims related to ALA.

[1019] Rawla P et al. Dysphagia, esophageal obstruction, and chia seeds 2017;35(8):1212.e1–1212.e2. Am J Emerg Med. 2017.

A case report (Am J Emerg Med) on dysphagia and esophageal obstruction associated with chia seeds.

[1020] Sandoval-Oliveros MR, Paredes-López O. Isolation and characterization of proteins from chia seeds (Salvia hispanica L.)2013;61(1):193–201. J Agric Food Chem. 2013. Link

Chia ( Salvia hispanica L.) is a plant that produces seeds rich in some nutraceutical compounds with high protein content, but little is known about them; for this reason the aim of this study was to characterize the seed storage proteins. Protein fractions were extracted from chia seed flour. The main protein fraction corresponded to globulins (52\%). Sedimentation coefficient studies showed that the globulin fraction contains mostly 11S and 7S proteins. The molecular sizes of all the reduced fractions were about 15-50 kDa. Electrophoretic experiments under native conditions exhibited four bands of globulins in the range of 104-628 kDa.

[1021] Knez Hrnčič M et al. Chia seeds (Salvia hispanica L.): an overview — phytochemical profile, isolation methods, and application2019;25(1):11. Molecules. Link

A review article (Molecules) providing an overview of chia seeds (Salvia hispanica L.), their phytochemical profile, isolation methods and application.

[1023] Kuijsten A et al. The relative bioavailability of enterolignans in humans is enhanced by milling and crushing of flaxseed2005;135(12):2812–2816. J Nutr. Link

Flaxseed is one of the richest sources of lignans and is increasingly used in food products or as a supplement. Plant lignans can be converted by intestinal bacteria into the so-called enterolignans, enterodiol and enterolactone. For a proper evaluation of potential health effects of enterolignans, information on their bioavailability is essential. The aim of this study was to investigate whether crushing and milling of flaxseed enhances the bioavailability of enterolignans in plasma. In a randomized, crossover study, 12 healthy subjects supplemented their diet with 0.3 g whole, crushed, or ground flaxseed/(kg body weight . d). Each subject consumed flaxseed for 10 successive days separated by 11-d run-in/wash-out periods, in which the subjects consumed a diet poor in lignans.

[1024] Brahe LK et al. Dietary modulation of the gut microbiota — a randomised controlled trial in obese postmenopausal women2015;114(3):406–417. Br J Nutr. Link

The gut microbiota has been implicated in obesity and its progression towards metabolic disease. Dietary interventions that target the gut microbiota have been suggested to improve metabolic health. The aim of the present study was to investigate the effect of interventions with Lactobacillus paracasei F19 or flaxseed mucilage on the gut microbiota and metabolic risk markers in obesity. A total of fifty-eight obese postmenopausal women were randomised to a single-blinded, parallel-group intervention of 6-week duration, with a daily intake of either L. paracasei F19 (9.4 × 1010 colony-forming units), flaxseed mucilage (10 g) or placebo. Quantitative metagenomic analysis of faecal DNA was performed to identify the changes in the gut microbiota. Diet-induced changes in metabolic markers were explored using adjusted linear regression models.

[1025] Soltanian N, Janghorbani M. A randomized trial of the effects of flaxseed to manage constipation, weight, glycemia, and lipids in constipated patients with type 2 diabetes 2018;15:36. Nutr Metab (Lond). 2018. Link

A single-blind, randomized controlled trial in 53 constipated patients with type 2 diabetes evaluated the effects of flaxseed. Patients received either 10 g of flaxseed pre-mixed in cookies twice daily or placebo cookies for 12 weeks. After the 12-week intervention, compared with baseline, constipation symptom scores improved significantly, and body weight (−3.8 kg), BMI, fasting plasma glucose, total cholesterol, triglycerides, and LDL-cholesterol decreased while HDL-cholesterol increased.

[1026] Khalesi S et al. Flaxseed consumption may reduce blood pressure: a systematic review and meta-analysis of controlled trials2015;145(4):758–765. J Nutr. Link

A systematic review and meta-analysis of controlled trials (J Nutr) on whether flaxseed consumption may reduce blood pressure.

[1027] Lowcock EC et al. Consumption of flaxseed, a rich source of lignans, is associated with reduced breast cancer risk 2013;24(4):813–816. Cancer Causes Control. 2013. Link

A case-control study (Ontario Women's Diet and Health Study, 2002-2003) examined the association between flaxseed intake -- the richest dietary source of lignans (phytoestrogens) -- and breast cancer risk. A food frequency questionnaire measured flaxseed and flax bread consumption in 2,999 women with breast cancer and 3,370 healthy controls; 21% of controls consumed flaxseed or flax bread at least weekly. The study reports an association between flaxseed consumption and reduced breast cancer risk.

[1028] Schrenk D et al. (EFSA Panel CONTAM). Evaluation of the health risks related to the presence of cyanogenic glycosides in foods other than raw apricot kernels 2019;17(4):e05662. EFSA Journal. 2019. Link

The EFSA CONTAM Panel evaluated the health risks related to the presence of cyanogenic glycosides (CNGs) in foods other than raw apricot kernels. The Panel considered its previously (2016) established acute reference dose (ARfD) for cyanide of 20 µg/kg bw to be applicable regardless of dietary source. Estimated mean acute cyanide exposure did not exceed the ARfD in any age group, but at the 95th percentile it was exceeded up to about 2.5-fold in some surveys for children and adolescents; the main contributors were biscuits, juice or nectar, and pastries and cakes.

[1029] Adolphe JL et al. Health effects with consumption of the flax lignan secoisolariciresinol diglucoside 2010;103(7):929–938. Br J Nutr. 2010. Link

This review summarizes the health effects of consuming the flax lignan secoisolariciresinol diglucoside (SDG). Flaxseed is the richest source of SDG; after ingestion, SDG is converted to secoisolariciresinol, which is further metabolized into the mammalian lignans enterodiol and enterolactone. The review discusses the potential health effects of SDG and its metabolites.

[1031] Penalvo JL et al. Quantification of lignans in food using isotope dilution gas chromatography/mass spectrometry2005;53(24):9342–9347. J Agric Food Chem. Link

A methodological J Agric Food Chem article on the quantification of lignans in food using isotope dilution gas chromatography/mass spectrometry.

[1032] Khalesi S et al. Sesame fractions and lipid profiles: a systematic review and meta-analysis of controlled trials2016;115(5):764–773. Br J Nutr. Link

Increased plasma lipid profiles are among the most important risk factors of CHD and stroke. Sesame contains considerable amounts of vitamin E, MUFA, fibre and lignans, which are thought to be associated with its plasma lipid-lowering properties. This study aimed to systematically review the evidence and identify the effects of sesame consumption on blood lipid profiles using a meta-analysis of controlled trials. PubMed, CINAHL and Cochrane Library databases were searched (from 1960 to May 2015). A total of ten controlled trials were identified based on the eligibility criteria. Both the Cochrane Collaboration tool and the Rosendal scale were used to assess the risk of bias of the included studies.

[1033] Wu WH et al. Sesame ingestion affects sex hormones, antioxidant status, and blood lipids in postmenopausal women2006;136(5):1270–1275. J Nutr. Link

Sesame ingestion has been shown to improve blood lipids in humans and antioxidative ability in animals. Sesamin, a sesame lignan, was recently reported to be converted by intestinal microflora to enterolactone, a compound with estrogenic activity and also an enterometabolite of flaxseed lignans, which are known to be phytoestrogens. Whether sesame can be a source of phytoestrogens is unknown. This study was designed to investigate the effect of sesame ingestion on blood sex hormones, lipids, tocopherol, and ex vivo LDL oxidation in postmenopausal women. Twenty-six healthy subjects attended, and 24 completed, this randomized, placebo-controlled, crossover study. Half of them consumed 50 g sesame seed powder daily for 5 wk, followed by a 3-wk washout period, then a 5-wk 50-g rice powder placebo period.

[1034] Coulman KD et al. Whole sesame seed is as rich a source of mammalian lignan precursors as whole flaxseed2005;52(2):156–165. Nutr Cancer. Link

The mammalian lignans enterolactone and enterodiol, which are produced by the microflora in the colon of humans and animals from precursors in foods, have been suggested to have potential anticancer effects. This study determined the production of mammalian lignans from precursors in food bars containing 25 g unground whole flaxseed (FB), sesame seed (SB), or their combination (FSB; 12.5 g each). In a randomized crossover study, healthy postmenopausal women supplemented their diets with the bars for 4 wk each separated by 4-wk washout periods, and urinary mammalian lignan excretion was measured at baseline and after 4 wk as a marker of mammalian lignan production. Results showed an increase with all treatments (65.1-81.0 mumol/day; P < 0.0001), which did not differ among treatments. Lignan excretion with the whole flaxseed was similar to results of other studies using ground flaxseed. An unidentified lignan metabolite was detected after consumption of SB and FSB but not of FB.

[1035] Warren CM et al. Prevalence and severity of sesame allergy in the United States2019;2(8):e199144. JAMA Netw Open. Link

Epidemiological study (JAMA Netw Open) on the prevalence and severity of sesame allergy in the United States.

[1036] FDA. FASTER Act of 2021 — sesame as the 9th major food allergen. Effective January 1, 2023. . 2021. Link

The FDA's FASTER Act of 2021, designating sesame as the 9th major food allergen in the United States (effective January 1, 2023).

[1037] Pathak N et al. Bioactive constituents of Sesamum indicum: a comprehensive review 2014. J Pharm Pharmacol. 2014.

A comprehensive review article (J Pharm Pharmacol) on the bioactive constituents of Sesamum indicum.

[1039] Cabello-Olmo M et al. Tiger nut (Cyperus esculentus) consumption modulates gut microbiota and short-chain fatty acid production in healthy adults: a pilot study 2021;13(6):1903. Nutrients. 2021.

A pilot study (Nutrients) on how tiger nut (Cyperus esculentus) consumption modulates gut microbiota and short-chain fatty acid production in healthy adults.

[1040] Macho GA. Baboon feeding ecology informs the dietary niche of Paranthropus boisei2014;9(1):e84942. PLOS ONE. Link

A PLOS ONE article using baboon feeding ecology to inform the dietary niche of Paranthropus boisei.

[1041] Sánchez-Zapata E et al. Tiger nut (Cyperus esculentus) commercialization: health aspects, composition, properties, and food applications 2012;11(4):366–377. Compr Rev Food Sci Food Saf. 2012. Link

This review discusses the commercialization of tiger nut (Cyperus esculentus), covering its health aspects, composition, properties, and food applications. Tiger nut is rich in starch (26-38%) and lipid (19-41%), with abundant oleic acid and glucose, as well as phosphorus, potassium, and vitamins C and E, and its cell walls contain various antioxidant phenols. In Spain it is mainly used to produce a milky beverage called "horchata de chufa".

[1042] Roselló-Soto E et al. Tiger nut and its by-products valorization: from extraction of oil and valuable compounds to development of novel healthy products 2018. Innov Food Sci Emerg Technol. 2018. Link

This review discusses the valorization of tiger nut (Cyperus esculentus) and its by-products, from the extraction of oil and valuable compounds to the development of new healthy products. The authors evaluated conventional (Soxhlet) and innovative (e.g., supercritical CO2) extraction methods for the efficient recovery of tiger nut oil and high-added-value compounds (monounsaturated fatty acids, phytosterols, vitamin E, phenolic acids). They highlight the potential of by-products in developing fibre-rich, oxidatively stable functional products.

[1043] Bamishaiye EI, Bamishaiye OM. Tiger nut: as a plant, its derivatives and benefits 2011;11(5):5157–5170. Afr J Food Agric Nutr Dev. 2011.

A review article (Afr J Food Agric Nutr Dev) on tiger nut as a plant, its derivatives and benefits.

[1044] Pascual B et al. Chufa (Cyperus esculentus L. var. sativus Boeck.): an unconventional crop — studies related to applications and cultivation 2000;54(4):439–448. Econ Bot. 2000. Link

This paper discusses the cultivation and applications of chufa (Cyperus esculentus L. var. sativus Boeck.) as an unconventional crop, drawing on the results of a twenty-year research program (nutrition, fertilization, lodging control, planting date, soil texture, herbicide use). The authors describe new uses: chufa as a source of dietary fibre, as a high-quality cooking/salad oil or biodiesel, as caramel, as a source of starch, and as an antioxidant-containing food.

[1045] Cortés C et al. Determination of carotenoids, vitamins A and E, and crystalline carbohydrates in tiger nut 2005. Food Chem. 2005.

A Food Chem article on the determination of carotenoids, vitamins A and E, and crystalline carbohydrates in tiger nut.

[1047] . EMA/HMPC 2013. Community herbal monograph on Plantago ovata Forssk., seminis tegumentum. 2013. Link

An EMA/HMPC community herbal monograph on Plantago ovata Forssk., seminis tegumentum (seed husk).

[1048] Jalanka J et al. The effect of psyllium husk on intestinal microbiota in constipated patients and healthy controls2019;20(2):433. Int J Mol Sci. Link

An Int J Mol Sci article on the effect of psyllium husk on intestinal microbiota in constipated patients and healthy controls.

[1049] Christodoulides S et al. Systematic review with meta-analysis: effect of fibre supplementation on chronic idiopathic constipation in adults2016;44(2):103–116. Aliment Pharmacol Ther. Link

BACKGROUND: Chronic idiopathic constipation is a common symptom-based gastrointestinal disorder responsible for a substantial economic health service burden. Current guidelines recommend the use of fibre as a first-line treatment. AIM: To investigate the effect of fibre (including prebiotic) supplementation on global symptom response, stool output, gut microbiota composition and adverse events in adults with chronic idiopathic constipation. METHODS: Medline, EmBase, Web of Science, Scopus and the Cochrane central register of controlled trials were searched through to February 2016. Conference proceedings from 2003 to 2015 were hand-searched. There were no language restrictions.

[1050] Moayyedi P et al. The effect of fiber supplementation on irritable bowel syndrome: a systematic review and meta-analysis2014;109(9):1367–1374. Am J Gastroenterol. Link

OBJECTIVES: Fiber has been used for many years to treat irritable bowel syndrome (IBS). This approach had fallen out of favor until a recent resurgence, which was based on new randomized controlled trial (RCT) data that suggested it might be effective. We have previously conducted a systematic review of fiber in IBS, but new RCT data for fiber therapy necessitate a new analysis; thus, we have conducted a systematic review of this intervention. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched up to December 2013. Trials recruiting adults with IBS, which compared fiber supplements with placebo, control therapy, or "usual management", were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy as well as number needed to treat (NNT) with a 95\% confidence interval (CI).

[1051] Lambeau KV, McRorie JW. Fiber supplements and clinically proven health benefits 2017;29(4):216–223. J Am Assoc Nurse Pract. 2017.

A review article (J Am Assoc Nurse Pract) on fiber supplements and clinically proven health benefits.

[1052] Ramkumar D, Rao SS. Efficacy and safety of traditional medical therapies for chronic constipation: systematic review 2005;100(4):936–971. Am J Gastroenterol. 2005. Link

A systematic review of the efficacy and safety of traditional medical therapies for chronic constipation, based on randomized trials in adults published as full manuscripts (MEDLINE/PUBMED, 1966-2003). The results showed good evidence (Grade A) for polyethylene glycol (PEG) and tegaserod, and moderate evidence (Grade B) for psyllium and lactulose. For many commonly used agents (milk of magnesia, senna, bisacodyl, stool softeners), there was a paucity of quality data.

[1053] Gunn D et al. Psyllium reduces inulin-induced colonic gas production in IBS 2020. Gut. 2020.

A Gut article on psyllium reducing inulin-induced colonic gas production in IBS.

[1054] ACG (American College of Gastroenterology). Clinical guideline: management of irritable bowel syndrome 2021. Am J Gastroenterol. 2021.

An ACG (American College of Gastroenterology) clinical guideline (Am J Gastroenterol) on the management of irritable bowel syndrome.

[1055] FDA. Health claim — soluble fiber from psyllium husk and risk of coronary heart disease, 1998. 21 CFR 101.81. 1998. Link

An FDA health claim (1998, 21 CFR 101.81) on soluble fiber from psyllium husk and risk of coronary heart disease.

[1056] Thomson CD et al. Brazil nuts: an effective way to improve selenium status. Am J Clin Nutr 2008;87(2):379–384. . 2008. Link

BACKGROUND: Brazil nuts provide a rich natural source of selenium, yet no studies have investigated the bioavailability of selenium in humans. OBJECTIVE: We investigated the efficacy of Brazil nuts in increasing selenium status in comparison with selenomethionine. DESIGN: A randomized controlled trial was conducted with 59 New Zealand adults. Participants consumed 2 Brazil nuts thought to provide approximately 100 mug Se, 100 mug Se as selenomethionine, or placebo daily for 12 wk. Actual intake from nuts averaged 53 mug Se/d (possible range: 20-84 mug Se). Plasma selenium and plasma and whole blood glutathione peroxidase (GPx) activities were measured at baseline and at 2, 4, 8, and 12 wk, and effects of treatments were compared.

[1057] Stockler-Pinto MB et al. Effect of Brazil nut supplementation on the blood levels of selenium and glutathione peroxidase in hemodialysis patients. Nutrition 2010;26(11–12):1065–1069. . 2010. Link

In hemodialysis patients who were selenium-deficient at baseline, the effect of consuming one Brazil nut per day (approximately 290 µg selenium) for three months was assessed. Supplementation significantly increased blood selenium levels and glutathione peroxidase (GSH-Px) activity, indicating attenuated oxidative stress. The authors conclude that Brazil nut, as a rich dietary selenium source, can effectively enhance antioxidant defenses in this population.

[1058] Kerdel-Vegas F. The depilatory and cytotoxic action of "Coco de Mono" (Lecythis ollaria) and its relationship to chronic seleniosis. Econ Bot 1966;20(2):187–195. . 1966. Link

Kerdel-Vegas built on clinical observations of temporary hair loss (alopecia) following ingestion of Lecythis ollaria ("coco de mono") nuts, accompanied by acute intoxication, fever, diarrhea, and neurological manifestations. The marked cytotoxic effect of the nut was demonstrated in vitro on mouse fibroblasts, and the active principle was isolated and identified as the selenium analog of the sulfur amino acid cystathionine. The work linked these depilatory and cytotoxic effects to chronic seleniosis.

[1059] Toulis KA et al. Selenium supplementation in the treatment of Hashimoto's thyroiditis: a systematic review and meta-analysis. Thyroid 2010;20(10):1163–1173. . 2010. Link

A systematic review and meta-analysis of selenium supplementation as adjunctive therapy to levothyroxine in the treatment of Hashimoto's thyroiditis. Pooled results showed significantly lower anti-TPO (thyroid peroxidase) antibody titers after only 3 months of supplementation, along with improvement in mood and general well-being. The authors interpret the clinical benefit cautiously given the limited strength of evidence.

[1060] Stranges S et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med 2007;147(4):217–223. . 2007. Link

A secondary analysis of a randomized, double-blind, placebo-controlled trial (1202 participants without type 2 diabetes at baseline) in low-selenium areas of the eastern United States, using 200 µg/day selenium. Over an average 7.7-year follow-up, more new cases of type 2 diabetes developed in the selenium group than in the placebo group (58 vs. 39 cases). The finding cautions that long-term selenium supplementation may increase type 2 diabetes risk in selenium-replete individuals.

[1061] Hadrup N, Ravn-Haren G. Acute human toxicity and mortality after selenium ingestion: a review. J Trace Elem Med Biol 2020;58:126435. . 2020. Link

A review (J Trace Elem Med Biol) on acute human toxicity and mortality after selenium ingestion.

[1062] Silva Junior EC et al. Natural variation of selenium in Brazil nuts and soils from the Amazon region. Chemosphere 2017;188:650–658. . 2017. Link

This study examined the natural variation of selenium content in Brazil nuts and their soils across the Amazon region. Selenium content in nuts varied widely by region (the study reports roughly 2 mg/kg up to more than 68 mg/kg), and uptake was governed less by total soil selenium than by other soil properties such as acidity and selenium availability. It was the first study to directly relate soil properties to selenium accumulation in Brazil nuts.

[1063] Combs GF Jr. Selenium in global food systems. Br J Nutr 2001;85(5):517–547. . 2001. Link

A comprehensive review of the role of selenium in global food systems and human health. It discusses that food systems must supply sufficient selenium to support maximal expression of selenoenzymes (an adult intake of at least ~40 µg/day) and collates data on the selenium status of populations worldwide. It emphasizes that selenium deprivation impairs antioxidant protection, redox regulation, and energy production.

[1064] EFSA. Scientific opinion on dietary reference values for selenium. EFSA Journal 2014;12(10):3846. . 2014. Link

An EFSA Scientific Opinion (EFSA Journal) on dietary reference values for selenium.

[1065] Vahlensieck W et al. Effects of pumpkin seed in men with lower urinary tract symptoms due to benign prostatic hyperplasia in the one-year, randomized, placebo-controlled GRANU study. Urol Int 2015;94(3):286–295. . 2015. Link

A one-year, randomized, placebo-controlled trial (Urol Int, GRANU study) on the effect of pumpkin seed in men with lower urinary tract symptoms due to benign prostatic hyperplasia.

[1066] Hudson C et al. Protein source tryptophan versus pharmaceutical grade tryptophan as an efficacious treatment for chronic insomnia. Nutr Neurosci 2005;8(2):121–127. . 2005. Link

A randomized comparative study in chronic insomnia comparing tryptophan from a protein source (deoiled gourd seed, ~22 mg tryptophan/g protein) given with glucose against pharmaceutical-grade tryptophan (with carbohydrate) and carbohydrate alone. Both natural-protein-source and pure tryptophan improved subjective and objective sleep measures in insomniacs. The authors suggest the natural source may be similarly efficacious yet potentially safer.

[1067] Strate LL et al. Nut, corn, and popcorn consumption and the incidence of diverticular disease. JAMA 2008;300(8):907–914. . 2008. Link

A JAMA article on nut, corn and popcorn consumption and the incidence of diverticular disease.

[1068] Damiano R et al. The role of Cucurbita pepo in the management of patients affected by lower urinary tract symptoms due to benign prostatic hyperplasia: a narrative review. Arch Ital Urol Androl 2016;88(2):136–143. . 2016. Link

A narrative review of the role of Cucurbita pepo (pumpkin/pumpkin seed) in managing lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). After a database search, 16 relevant articles were analyzed (10 in vitro, showing anti-inflammatory and antiandrogen effects; 6 clinical). The clinical studies consistently reported improvements in the International Prostatic Symptoms Score (IPSS) and uroflowmetry, though the authors note further trials are needed to confirm these promising results.

[1069] Yadav M et al. Medicinal and biological potential of pumpkin: an updated review. Nutr Res Rev 2010;23(2):184–190. . 2010. Link

An updated review of the medicinal and biological potential of pumpkin (Cucurbita). It describes that pumpkin contains numerous phytoconstituents (alkaloids, flavonoids, palmitic, oleic and linoleic acids) and that the literature ascribes to it antidiabetic, antihypertensive, antitumor, immunomodulatory, antibacterial, hypocholesterolemic, intestinal antiparasitic, anti-inflammatory, and analgesic effects. As a review, it primarily synthesizes the existing literature.

[1070] EMA/HMPC. Community herbal monograph on Cucurbita pepo L., semen. 2012. . 2012. Link

An EMA/HMPC community herbal monograph on Cucurbita pepo L., semen (seed).

[1071] USDA FoodData Central. Seeds, pumpkin and squash seed kernels — FDC ID 170557. Link

A USDA FoodData Central database entry (FDC ID 170557) for pumpkin and squash seed kernels.

[1072] Glew RH et al. Amino acid, mineral and fatty acid content of pumpkin seeds (Cucurbita spp.) and Cyperus esculentus nuts in the Republic of Niger. Plant Foods Hum Nutr 2006;61(2):51–56. . 2006. Link

This study analyzed the nutrient composition of Cucurbita spp. pumpkin seeds and Cyperus esculentus nuts in the Republic of Niger, where these seeds are widely consumed. On a dry-weight basis, pumpkin seed was high in protein (~58.8%) and fat (~29.8%), with useful amounts of linoleic acid and minerals (e.g., potassium, magnesium, zinc) but low calcium and iron; the protein's lysine score was only ~65% relative to the FAO/WHO standard. The study characterized these seeds as dietary resources for indigenous western Sahel populations.

[1073] EFSA NDA Panel. Scientific Opinion on pectins and maintenance of normal blood cholesterol concentrations2010;8(10):1747. EFSA Journal. Link

A Scientific Opinion of the EFSA NDA Panel (EFSA Journal) on pectins and the maintenance of normal blood cholesterol concentrations.

[1074] EFSA NDA Panel. Scientific Opinion on pectins and reduction of post-prandial glycaemic responses2010;8(10):1747. EFSA Journal. Link

A Scientific Opinion of the EFSA NDA Panel (EFSA Journal) on pectins and the reduction of post-prandial glycaemic responses.

[1075] FDA. Health claims: soluble fiber from certain foods and risk of coronary heart disease. 21 CFR 101.81. Link

An FDA health claim (21 CFR 101.81) on soluble fiber from certain foods and risk of coronary heart disease.

[1076] Koutsos A et al. Apples and cardiovascular health: is the gut microbiota a core consideration?2015;7(6):3959-3998. Nutrients. 2015. Link

There is now considerable scientific evidence that a diet rich in fruits and vegetables can improve human health and protect against chronic diseases. However, it is not clear whether different fruits and vegetables have distinct beneficial effects. Apples are among the most frequently consumed fruits and a rich source of polyphenols and fiber. A major proportion of the bioactive components in apples, including the high molecular weight polyphenols, escape absorption in the upper gastrointestinal tract and reach the large intestine relatively intact. There, they can be converted by the colonic microbiota to bioavailable and biologically active compounds with systemic effects, in addition to modulating microbial composition. Epidemiological studies have identified associations between frequent apple consumption and reduced risk of chronic diseases such as cardiovascular disease.

[1077] Tenore GC et al. Annurca apple polyphenols influence the gut microbiota of healthy subjects 2017;8(5):1837-1846. Food Funct. 2017.

A Food Funct article on how Annurca apple polyphenols influence the gut microbiota of healthy subjects.

[1078] Ravn-Haren G et al. Intake of whole apples or clear apple juice has contrasting effects on plasma lipids in healthy volunteers 2013;52(8):1875-1889. Eur J Nutr. 2013. Link

A dietary crossover study (5x4 weeks) in 23 healthy volunteers comparing the effects of whole apples (550 g/day), apple pomace (22 g/day), clear and cloudy apple juice (500 ml/day), and no supplement on plasma lipids. Whole apples, pomace, and cloudy juice trended toward lower LDL-cholesterol, whereas clear juice raised it relative to whole apples. The authors conclude the fibre component is necessary for the cholesterol-lowering effect of apples and that clear juice is not a suitable surrogate for whole fruit.

[1079] Davis MA et al. Association between apple consumption and physician visits2015;175(5):777-783. JAMA Intern Med. Link

IMPORTANCE: Fruit consumption is believed to have beneficial health effects, and some claim, "An apple a day keeps the doctor away." OBJECTIVE: To examine the relationship between eating an apple a day and keeping the doctor away. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study of a nationally representative sample of the noninstitutionalized US adult population. A total of 8728 adults 18 years and older from the 2007-2008 and 2009-2010 National Health and Nutrition Examination Survey completed a 24-hour dietary recall questionnaire and reported that the quantity of food they ate was reflective of their usual daily diet. EXPOSURES: Daily apple eaters (consuming the equivalent of at least 1 small apple daily, or 149 g of raw apple) vs non-apple eaters, based on the reported quantity of whole apple consumed during the 24-hour dietary recall period. MAIN OUTCOMES AND MEASURES: The primary outcome measure was success at "keeping the doctor away," measured as no more than 1 visit (self-reported) to a physician during the past year; secondary outcomes included successful avoidance of other health care services (ie, no overnight hospital stays, visits to a mental health professional, or prescription medications). RESULTS: Of 8399 eligible study participants who completed the dietary recall questionnaire, we identified 753 adult apple eaters (9.0\%)--those who typically consume at least 1 small apple per day.

[1080] Cornille A et al. New insight into the history of domesticated apple2012;8(5):e1002703. PLoS Genet. Link

PLoS Genetics population-genetics/genomics study examining the origin and evolutionary history of the domesticated apple (Malus).

[1081] Boyer J, Liu RH. Apple phytochemicals and their health benefits2004;3:5. Nutr J. Link

Evidence suggests that a diet high in fruits and vegetables may decrease the risk of chronic diseases, such as cardiovascular disease and cancer, and phytochemicals including phenolics, flavonoids and carotenoids from fruits and vegetables may play a key role in reducing chronic disease risk. Apples are a widely consumed, rich source of phytochemicals, and epidemiological studies have linked the consumption of apples with reduced risk of some cancers, cardiovascular disease, asthma, and diabetes. In the laboratory, apples have been found to have very strong antioxidant activity, inhibit cancer cell proliferation, decrease lipid oxidation, and lower cholesterol. Apples contain a variety of phytochemicals, including quercetin, catechin, phloridzin and chlorogenic acid, all of which are strong antioxidants. The phytochemical composition of apples varies greatly between different varieties of apples, and there are also small changes in phytochemicals during the maturation and ripening of the fruit. Storage has little to no effect on apple phytochemicals, but processing can greatly affect apple phytochemicals.

[1083] Reiland H, Slavin J. Systematic review of pears and health2015;50(6):301-305. Nutr Today. Link

Nutrition Today systematic review of the relationships between pear consumption and health.

[1084] EFSA NDA Panel. Scientific Opinion on pectins2010;8(10):1747. EFSA Journal. Link

EFSA NDA Panel scientific opinion on pectins, published in the EFSA Journal.

[1085] Li X et al. Composition and biological activities of polyphenols in pear fruits 2015;6(3):745-756. Food Funct. 2015.

Food & Function study examining the composition and biological activities of polyphenols in pear fruits.

[1086] Salta J et al. Antioxidant phenolic compounds in selected pear varieties 2010;90(7):1230-1235. J Sci Food Agric. 2010.

Journal of the Science of Food and Agriculture article examining antioxidant phenolic compounds in selected pear varieties.

[1088] Wojdyło A et al. Polyphenolic compounds and antioxidant activity of new and old apple and pear varieties 2014;19(11):18650-18669. Molecules. 2014.

Molecules study examining the polyphenolic compounds and antioxidant activity of new and old apple and pear varieties.

[1089] USDA FoodData Central. Pears, raw — full nutrient profile. Link

USDA FoodData Central database entry for the full nutrient profile of raw pears.

[1090] Fang Z et al. Pectin from pear pomace: extraction and prebiotic effects 2022;278:118970. Carbohydr Polym. 2022.

Carbohydrate Polymers article on the extraction and prebiotic effects of pectin from pear pomace.

[1091] Chan AO et al. Increasing dietary fiber intake in terms of kiwifruit improves constipation in Chinese patients2007;13(35):4771-4775. World J Gastroenterol. Link

AIM: To investigate if increased dietary fiber, in terms of kiwifruit, is effective in Chinese constipated patients. METHODS: 33 constipated patients and 20 healthy volunteers were recruited for a 4-wk treatment of kiwi fruit twice daily. Response during wk 1-4 was defined as an increase in complete spontaneous bowl, motion (CSBM) > or = 1/wk. Secondary efficacy included response during wk 1-4, individual symptoms and scores of bowel habits and constipation. Responses were compared with the baseline run-in period. Colonic transit time and anorectal manometry were performed before and after treatment.

[1092] Eady SL et al. The effect of 'Zesy002' kiwifruit (Actinidia chinensis var. chinensis) on gut health function: a randomised cross-over clinical trial 2019;8:e18. J Nutr Sci. 2019. Link

A randomized, single-blind crossover clinical trial (32 participants, 16 weeks) comparing the effect of three 'Zesy002' kiwifruit (Actinidia chinensis var. chinensis) daily against Metamucil (5 g fibre/day, positive control) on gut function over 4-week treatment periods. During kiwifruit consumption, the number of complete spontaneous bowel movements per week was significantly greater than at baseline and than with Metamucil, and stool consistency improved (softer stools, less straining). The results support a beneficial effect of kiwifruit on gut function.

[1093] Bayer SB et al. Two kiwifruit a day for functional constipation: a randomized controlled trial2022;55(8):961-973. Aliment Pharmacol Ther. Link

Alimentary Pharmacology & Therapeutics randomized controlled trial of consuming two kiwifruit a day for functional constipation.

[1094] Chan AO et al. Kiwifruit vs. psyllium in IBS-C: randomised crossover trial 2021;53(11):1207-1216. Aliment Pharmacol Ther. 2021.

Alimentary Pharmacology & Therapeutics randomised crossover trial comparing kiwifruit with psyllium in constipation-predominant IBS (IBS-C).

[1095] Kaur L et al. Actinidin enhances gastric protein digestion in humans 2010;58(8):5068-5073. J Agric Food Chem. 2010.

Journal of Agricultural and Food Chemistry human study of how actinidin enhances gastric protein digestion.

[1096] Blatchford P et al. Kiwifruit fermentation drives changes in human gut microbiota 2017;6:e52. J Nutr Sci. 2017.

Journal of Nutritional Science study examining changes in the human gut microbiota driven by kiwifruit fermentation.

[1097] Drummond L. The composition and nutritional value of kiwifruit 2013;68:33-57. Adv Food Nutr Res. 2013.

Advances in Food and Nutrition Research review chapter on the composition and nutritional value of kiwifruit.

[1098] Lucas-González R et al. Actinidin: properties and food applications 2021;10(7):1611. Foods. 2021.

Foods review of the properties and food applications of actinidin.

[1099] Lucas JS et al. Kiwifruit allergy: a review 2003;14(6):420-428. Pediatr Allergy Immunol. 2003.

Pediatric Allergy and Immunology review of kiwifruit allergy.

[1101] González-Sarrías A et al. Clustering of pomegranate ETs-metabolising enterotypes in humans 2017;61(5):1600830. Mol Nutr Food Res. 2017.

Molecular Nutrition & Food Research study examining the clustering of pomegranate ellagitannin (ET)-metabolising enterotypes in humans.

[1102] Espín JC, García-Conesa MT, Tomás-Barberán FA. Nutraceuticals: facts and fiction 2007;68(22-24):2986-3008. Phytochemistry. 2007. Link

A review of nutraceuticals contrasting the scientific knowledge on polyphenol bioavailability and biological activity ('fact') with the often poorly substantiated health claims ascribed to polyphenol-containing products ('fiction'). It discusses anthocyanins, proanthocyanidins, flavanones, isoflavones, resveratrol, and ellagic acid. The authors conclude that while the biological activity of many food phytochemicals is scientifically supported, the health claims attached to marketed nutraceutical products often have little or doubtful scientific foundation.

[1103] Xia H, Zhang Y, Zhang Y et al. Pomegranate juice supplemented with inulin modulates gut microbiota and promotes the production of microbiota-associated metabolites in overweight/obese individuals: a randomized, double-blind, placebo-controlled trial 2024;72(15):8472-8484. J Agric Food Chem. 2024. Link

A randomized, double-blind, placebo-controlled trial in 68 overweight/obese individuals (25<=BMI<=35) who received 200 mL/day pomegranate juice (PJ), PJ supplemented with inulin (PJ+inulin), or placebo for 3 weeks. Anthropometric and blood biochemical indicators did not change significantly over 3 weeks, but there was an increasingly significant effect from placebo to PJ to PJ+inulin on gut microbiota composition. PJ+inulin promoted the production of microbiota-associated short-chain fatty acids and pomegranate polyphenol metabolites.

[1104] Andreux PA et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans2019;1(6):595-603. Nat Metab. Link

Nature Metabolism human study examining the safety of the mitophagy activator urolithin A and a molecular signature of improved mitochondrial and cellular health.

[1105] Tomás-Barberán FA et al. Urolithins, the rescue of "old" metabolites to understand a "new" concept2017;61(1):1500901. Mol Nutr Food Res. Link

[1106] Cerdá B et al. Identification of urolithin A as a metabolite produced by human colon microflora from ellagic acid 2005;44(8):491-499. Eur J Nutr. 2005. Link

An in vitro fermentation study in which fecal samples from six volunteers were incubated under anaerobic conditions with ellagic acid, the ellagitannin punicalagin, and an ellagitannin-rich walnut extract. Urolithin A was produced from these sources in all fecal cultures, albeit at very different production rates and concentrations. The work identified urolithin A as a metabolite produced by the human colon microflora from ellagic acid and related compounds.

[1107] Selma MV et al. The gut microbiota metabolism of pomegranate or walnut ETs yields urolithins 2014;5(8):1779-1784. Food Funct. 2014.

Food & Function study examining the gut microbiota metabolism of pomegranate or walnut ellagitannins (ET) yielding urolithins.

[1108] Larrosa M et al. Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A2010;54(3):311-322. Mol Nutr Food Res. Link

Whether the beneficial effects of pomegranate are due to the ellagitannins or to their microbiota-derived urolithins is not known. Our objectives were to evaluate the effects of pomegranate intake and its main microbiota-derived metabolite urolithin-A (UROA) on colon inflammation and to assess whether UROA is the main anti-inflammatory compound. In addition, the effect of the inflammation on the phenolic metabolism was also explored. Male Fisher rats were fed with 250 mg kg(-1) day(-1) pomegranate extract (PE) or 15 mg kg(-1) day(-1) UROA for 25 days. Dextran sodium sulfate (5\%) (DSS) was administered for the five last days and then rats were euthanized. DSS is a well-known model of inflammatory bowel disease.

[1110] Queipo-Ortuño MI et al. Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers2012;95(6):1323-1334. Am J Clin Nutr. Link

BACKGROUND: Few studies have investigated the effect of dietary polyphenols on the complex human gut microbiota, and they focused mainly on single polyphenol molecules and select bacterial populations. OBJECTIVE: The objective was to evaluate the effect of a moderate intake of red wine polyphenols on select gut microbial groups implicated in host health benefits. DESIGN: Ten healthy male volunteers underwent a randomized, crossover, controlled intervention study. After a washout period, all of the subjects received red wine, the equivalent amount of de-alcoholized red wine, or gin for 20 d each. Total fecal DNA was submitted to polymerase chain reaction(PCR)-denaturing gradient gel electrophoresis and real-time quantitative PCR to monitor and quantify changes in fecal microbiota. Several biochemical markers were measured.

[1111] Yang J et al. Standardized whole grape powder modulates the human gut microbiota and cholesterol metabolism2021;151(3):686-695. J Nutr. Link

Human nutrition study (J Nutr) on how standardized whole grape powder modulates the human gut microbiota and cholesterol metabolism.

[1112] Sano A et al. Beneficial clinical effects of grape seed proanthocyanidin extract on the progression of carotid atherosclerotic plaques2007;53(2):174-182. J Nutr Sci Vitaminol (Tokyo). Link

Clinical study (J Nutr Sci Vitaminol) on the beneficial effects of grape seed proanthocyanidin extract on the progression of carotid atherosclerotic plaques.

[1113] Tresserra-Rimbau A et al. Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial2014;12:77. BMC Med. Link

BMC Medicine paper examining the association between polyphenol intake and mortality risk through a re-analysis of the PREDIMED trial.

[1114] Castro-Barquero S et al. Dietary polyphenol intake is associated with HDL-cholesterol and a better profile of other components of the metabolic syndrome2020;12(3):689. Nutrients. Link

Nutrients study examining associations of dietary polyphenol intake with HDL-cholesterol and other components of the metabolic syndrome.

[1115] McGovern PE et al. Beginning of viniculture in France2013;110(25):10147-10152. PNAS. Link

PNAS archaeological/biomolecular study on the beginning of viniculture in France.

[1116] Janssens PL et al. Acute effects of a single dose of resveratrol on satiety and appetite in healthy lean men 2017;110:177-184. Appetite. 2017.

Appetite study examining the acute effects of a single dose of resveratrol on satiety and appetite in healthy lean men.

[1117] . Monash University. High and Low FODMAP foods —. 2024. Link

Monash University FODMAP database listing the classification of foods into high and low FODMAP categories.

[1118] EFSA NDA Panel. Scientific Opinion on the substantiation of health claims related to grape extract and antioxidant activity 2011;9(4):2030. EFSA Journal. 2011.

EFSA NDA Panel scientific opinion on the substantiation of health claims related to grape extract and antioxidant activity, in the EFSA Journal.

[1119] Morand C et al. Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers2011;93(1):73-80. Am J Clin Nutr. Link

BACKGROUND: Although numerous human studies have shown consistent effects of some polyphenol-rich foods on several intermediate markers for cardiovascular diseases, it is still unknown whether their action could be specifically related to polyphenols. OBJECTIVE: We investigated the effect of orange juice and its major flavonoid, hesperidin, on microvascular reactivity, blood pressure, and cardiovascular risk biomarkers through both postprandial and chronic intervention studies. DESIGN: Twenty-four healthy, overweight men (age 50-65 y) were included in a randomized, controlled, crossover study. Throughout the three 4-wk periods, volunteers daily consumed 500 mL orange juice, 500 mL control drink plus hesperidin (CDH), or 500 mL control drink plus placebo (CDP). All measurements and blood collections were performed in overnight-fasted subjects before and after the 4-wk treatment periods. The postprandial study was conducted at the beginning of each experimental period.

[1120] Constans J et al. HESPER-HEALTH protocol: hesperidin and cardiovascular health 2015;69(6):737-742. Eur J Clin Nutr. 2015.

European Journal of Clinical Nutrition paper on the HESPER-HEALTH protocol examining hesperidin and cardiovascular health.

[1121] Buscemi S et al. Effects of red orange juice intake on endothelial function and inflammatory markers2012;95(5):1089-1095. Am J Clin Nutr. Link

BACKGROUND: Oxidative and inflammatory stresses are involved in the pathogenesis of atherosclerosis. The consumption of fruit and vegetables is associated with improved health and reduced cardiovascular risk. Red oranges have a high content of antioxidant and antiinflammatory substances, but there is a paucity of data concerning their effects on cardiovascular biomarkers in subjects with increased cardiovascular risk. OBJECTIVE: We investigated the effect of red orange juice intake on endothelial function, oxidative stress, and markers of inflammation in subjects with increased cardiovascular risk. DESIGN: Nineteen nondiabetic subjects with increased cardiovascular risk (aged 27-56 y) were included in a randomized, placebo-controlled, single-blind crossover study and compared with 12 healthy, nonobese control subjects. In 2 periods of 7 d each with a 3-d interval, each participant alternatively received 500 mL red orange juice/d and 500 mL placebo/d in a random sequence.

[1122] Pereira-Caro G et al. Orange juice (poly)phenols are highly bioavailable in humans2014;100(5):1378-1384. Am J Clin Nutr. Link

BACKGROUND: We assessed the bioavailability of orange juice (poly)phenols by monitoring urinary flavanone metabolites and ring fission catabolites produced by the action of the colonic microbiota. OBJECTIVE: Our objective was to identify and quantify metabolites and catabolites excreted in urine 0-24 h after the acute ingestion of a (poly)phenol-rich orange juice by 12 volunteers. DESIGN: Twelve volunteers [6 men and 6 women; body mass index (in kg/m(2)): 23.9-37.2] consumed a low (poly)phenol diet for 2 d before first drinking 250 mL pulp-enriched orange juice, which contained 584 μmol (poly)phenols of which 537 μmol were flavanones, and after a 2-wk washout, the procedure was repeated, and a placebo drink was consumed. Urine collected for a 24-h period was analyzed qualitatively and quantitatively by using high-performance liquid chromatography-mass spectrometry (HPLC-MS) and gas chromatography-mass spectrometry (GC-MS). RESULTS: A total of 14 metabolites were identified and quantified in urine by using HPLC-MS after orange juice intake. Hesperetin-O-glucuronides, naringenin-O-glucuronides, and hesperetin-3'-O-sulfate were the main metabolites.

[1123] Tomás-Barberán FA, Andrés-Lacueva C. Polyphenols and health: current state and progress 2012;60(36):8773-8775. J Agric Food Chem. 2012. Link

A brief symposium introduction in J Agric Food Chem summarizing the latest advances presented at the 5th International Conference on Polyphenols and Health (Sitges, Spain, 2011). It outlines the current state and progress of polyphenol research in a framing/editorial capacity rather than as an original experimental study.

[1124] Bailey DG et al. Grapefruit-medication interactions: forbidden fruit or avoidable consequences?2013;185(4):309-316. CMAJ. 2013. Link

Review article (CMAJ) on grapefruit-medication interactions, their mechanisms and clinical consequences.

[1125] Wu T et al. Hesperidin gut microbiota interactions: a review 2020;60(8):1339-1353. Crit Rev Food Sci Nutr. 2020.

Critical Reviews in Food Science and Nutrition review of hesperidin–gut microbiota interactions.

[1126] . Lind J Edinburgh: Sands, Murray & Cochran, 1753. A Treatise of the Scurvy.

James Lind's 1753 book, A Treatise of the Scurvy (Edinburgh: Sands, Murray & Cochran), on scurvy.

[1128] Rabbani GH et al. Green banana-supplemented diet in the home management of acute and prolonged diarrhoea in children: a community-based trial in rural Bangladesh2010;15(10):1132-1139. Trop Med Int Health. Link

SUMMARY OBJECTIVE: To determine the effectiveness of green banana in the home management of acute (<7 days) or prolonged (≥ 7 days) diarrhoea at the community level. METHODS: A cluster randomized field trial was conducted among 2968 Bangladeshi rural children 6-36 months old. Wards (villages) were randomly assigned to either a standard care group or a standard care plus green banana group where mothers were instructed to add cooked green banana to the diets of diarrhoeal children. Through a village-based surveillance system, diarrhoeal morbidity data (severity, duration, compliance) were collected for 14 days. Treatment effects were determined by analysing cumulative probability of cure by testing Cox proportional hazards models and relative risk (RR). RESULTS: The cumulative probability of cure was significantly (P < 0.001) different in children receiving GB for both acute [hazard ratio (HR) = 0.63 (95\% CI: 0.56-0.67)] and prolonged diarrhoea [HR = 0.38 (95\% CI: 0.26-0.59)].

[1129] Pereira MdC et al. Green banana biomass: a nutritional approach for chronic functional constipation 2010;25(6):988-994. Nutr Hosp. 2010.

Nutrición Hospitalaria study examining green banana biomass as a nutritional approach for chronic functional constipation.

[1130] Menezes EW et al. Chemical composition and nutritional value of unripe banana flour (Musa cavendishii) 2011;66(3):231-237. Plant Foods Hum Nutr. 2011.

Plant Foods for Human Nutrition study examining the chemical composition and nutritional value of unripe banana flour (Musa cavendishii).

[1131] Englyst HN et al. Classification and measurement of nutritionally important starch fractions 1992;46 Suppl 2:S33-S50. Eur J Clin Nutr. 1992.

European Journal of Clinical Nutrition methodological paper on the classification and measurement of nutritionally important starch fractions.

[1134] Falcomer AL et al. Health benefits of green banana consumption: a systematic review2019;11(6):1222. Nutrients. Link

Nutrients systematic review of the health benefits of green banana consumption.

[1135] Denardin CC, Walter M. Resistant starch and its health implications 2020;50:e20200043. Cienc Rural. 2020.

Ciência Rural review of resistant starch and its health implications.

[1137] Venancio VP et al. Polyphenol-rich mango (Mangifera indica L.) ameliorate functional constipation symptoms in humans beyond equivalent amount of fiber2018;62(12):1701034. Mol Nutr Food Res. Link

SCOPE: Chronic constipation is a common gastrointestinal condition associated with intestinal inflammation and considerably impaired quality of life, affecting about 20\% of Americans. Dietary fiber and laxatives aid in its treatment but do not fully address all symptoms, such as intestinal inflammation. Mango (Mangifera indica L.), a fiber- and polyphenol-rich fruit may provide anti-inflammatory effects in constipation. METHODS AND RESULTS: The 4 week consumption of mango fruit (300 g) or the equivalent amount of fiber is investigated in otherwise healthy human volunteers with chronic constipation who are randomly assigned to either group. Blood and fecal samples and digestive wellness questionnaires are collected at the beginning and end of the study. Results show that mango consumption significantly improve constipation status (stool frequency, consistency, and shape) and increase gastrin levels and fecal concentrations of short chain fatty acid (valeric acid) while lowering endotoxin and interleukin 6 concentrations in plasma.

[1138] Barbosa Lima H et al. Fresh mango consumption and gut microbiota: a randomized controlled trial 2024;16(5):721. Nutrients. 2024.

Nutrients randomized controlled trial examining fresh mango consumption and the gut microbiota.

[1139] Kim H et al. Mango fruit polyphenols modify gut microbiota composition 2020;11(11):9982-9994. Food Funct. 2020.

Food & Function study examining how mango fruit polyphenols modify gut microbiota composition.

[1140] Lauricella M et al. Multifaceted health benefits of Mangifera indica L. (Mango)2017;9(5):525. Nutrients. 2017. Link

Nutrients review of the multifaceted health benefits of Mangifera indica L. (Mango).

[1141] Quirós-Sauceda AE et al. Mango (Mangifera indica L.) polyphenols: insights from animal models 2017;67:9-23. Trends Food Sci Technol. 2017.

Trends in Food Science & Technology review of mango (Mangifera indica L.) polyphenols, drawing on insights from animal models.

[1142] Imran M et al. Mangiferin: a natural miracle bioactive compound against lifestyle related disorders2017;16:84. Lipids Health Dis. Link

Lipids in Health and Disease review of mangiferin as a natural bioactive compound against lifestyle-related disorders.

[1143] Oliver-Cervelló L et al. Anacardiaceae cross-reactivity and mango contact dermatitis 2018;78(1):75-77. Contact Dermatitis. 2018.

Contact Dermatitis paper examining Anacardiaceae cross-reactivity and mango contact dermatitis.

[1145] USDA FoodData Central. Mangos, raw — full nutrient profile. Link

USDA FoodData Central database entry for the full nutrient profile of raw mangos.

[1146] Park E et al. Strawberry consumption modulates gut microbiota: a 6-week randomized controlled trial in obese adults 2022;14(13):2787. Nutrients. 2022.

Nutrients 6-week randomized controlled trial examining how strawberry consumption modulates the gut microbiota in obese adults.

[1147] Sandhu KV et al. Feasibility of a 10-week strawberry-rich intervention in older adults: gut microbiota and cognitive endpoints 2018;7:e18. J Nutr Sci. 2018.

Journal of Nutritional Science study examining the feasibility of a 10-week strawberry-rich intervention in older adults, with gut microbiota and cognitive endpoints.

[1148] Henning SM et al. Pomegranate ellagitannins stimulate the growth of Akkermansia muciniphila in vivo (mint a metabotípus-mechanizmus mintapélda) 2017;43:56-60. — eper-specifikus PK alternatíva: Lee S et al. Food Funct 2018;9(6):3214-3223. Anaerobe. 2017. Link

This study examined the relationship between pomegranate ellagitannins and the gut bacterium Akkermansia muciniphila (in vivo human samples and in vitro). About 70% of participants formed urolithin A from ellagitannins in the intestine, and urolithin A formation was associated with a high proportion of A. muciniphila in fecal samples (16S rRNA sequencing). In vitro, certain concentrations of pomegranate extract inhibited A. muciniphila growth, partly explaining the in vivo findings; this was the first report of A. muciniphila's role in ellagitannin hydrolysis. (The strawberry-specific PK alternative linked in the bibliographic entry, Lee et al. Food Funct 2018, is a separate publication.)

[1149] Puupponen-Pimiä R et al. Berry phenolics: antimicrobial properties and mechanisms of action against severe human pathogens 2013;65(suppl):20-26. Nutr Cancer. 2013.

Nutrition and Cancer paper examining the antimicrobial properties and mechanisms of action of berry phenolics against severe human pathogens.

[1150] Hannum SM. Potential impact of strawberries on human health: a review of the science 2004;44(1):1-17. Crit Rev Food Sci Nutr. 2004.

Critical Reviews in Food Science and Nutrition review of the potential impact of strawberries on human health.

[1151] Basu A et al. Strawberries decrease atherosclerotic markers in subjects with metabolic syndrome2010;30(7):462-469. Nutr Res. Link

Human study (Nutr Res) reporting that strawberries decrease atherosclerotic markers in subjects with metabolic syndrome.

[1152] Giampieri F et al. The strawberry: composition, nutritional quality, and impact on human health2012;28(1):9-19. Nutrition. Link

Strawberries are a common and important fruit in the Mediterranean diet because of their high content of essential nutrients and beneficial phytochemicals, which seem to have relevant biological activity in human health. Among these phytochemicals, anthocyanin and ellagitannins are the major antioxidant compounds. Although individual phytochemical constituents of strawberries have been studied for their biological activities, human intervention studies using whole fruits are still lacking. Here, the nutritional contribution and phytochemical composition of the strawberry are reviewed, as is the role played by the maturity, genotype, and storage effects on this fruit. Specific attention is focused on fruit absorption, metabolism, and the possible beneficial biological activity on human health.

[1153] Tomás-Barberán FA et al. Urolithins, the rescue of "old" metabolites2017;61(1):1500901. Mol Nutr Food Res. Link

[1155] Xiao D et al. Red raspberries supplementation modifies microbial composition and metabolism in prediabetic adults 2019;9(2):243-256. J Berry Res. 2019.

Journal of Berry Research study examining how red raspberry supplementation modifies microbial composition and metabolism in prediabetic adults.

[1156] Ludwig IA et al. New insights into the bioavailability of red raspberry anthocyanins and ellagitannins2015;89:758-769. Free Radic Biol Med. Link

Red raspberries, containing ellagitannins and cyanidin-based anthocyanins, were fed to volunteers and metabolites appearing in plasma and urine were analysed by UHPLC-MS. Anthocyanins were not absorbed to any extent with sub nmol/L concentrations of cyanidin-3-O-glucoside and a cyanidin-O-glucuronide appearing transiently in plasma. Anthocyanins excreted in urine corresponded to 0.007\% of intake. More substantial amounts of phase II metabolites of ferulic acid and isoferulic acid, along with 4'-hydroxyhippuric acid, potentially originating from pH-mediated degradation of cyanidin in the proximal gastrointestinal tract, appeared in urine and also plasma where peak concentrations were attained 1-1.5h after raspberry intake. Excretion of 18 anthocyanin-derived metabolites corresponded to 15.0\% of intake, a figure substantially higher than obtained in other anthocyanin feeding studies. Ellagitannins pass from the small to the large intestine where the colonic microbiota mediate their conversion to urolithins A and B which appeared in plasma and were excreted almost exclusively as sulfate and glucuronide metabolites.

[1157] Burton-Freeman BM et al. Red raspberries and their bioactive polyphenols: cardiometabolic and neuronal health links2016;7(1):44-65. Adv Nutr. Link

Diet is an essential factor that affects the risk of modern-day metabolic diseases, including cardiovascular disease, diabetes mellitus, obesity, and Alzheimer disease. The potential ability of certain foods and their bioactive compounds to reverse or prevent the progression of the pathogenic processes that underlie these diseases has attracted research attention. Red raspberries (Rubus idaeus L.) are unique berries with a rich history and nutrient and bioactive composition. They possess several essential micronutrients, dietary fibers, and polyphenolic components, especially ellagitannins and anthocyanins, the latter of which give them their distinctive red coloring. In vitro and in vivo studies have revealed various mechanisms through which anthocyanins and ellagitannins (via ellagic acid or their urolithin metabolites) and red raspberry extracts (or the entire fruit) could reduce the risk of or reverse metabolically associated pathophysiologies. To our knowledge, few studies in humans are available for evaluation.

[1158] Mazur SP et al. Quality and chemical composition of ten red raspberry cultivars 2014;160:233-240. Food Chem. 2014.

Food Chemistry study examining the quality and chemical composition of ten red raspberry cultivars.

[1159] McDougall GJ et al. Anthocyanins from red wine — their stability under simulated gastrointestinal digestion 2005;66(21):2540-2548. Phytochemistry. 2005. Link

This study examined the stability of red-wine anthocyanins during simulated gastrointestinal digestion. Anthocyanins remained stable under gastric conditions (only small loss of total phenols), but after pancreatic digestion they were poorly recovered in the 'serum-available' fraction, with most recovered in the 'colon-available' fraction. Vitisin A-like modified aglycones were considerably more stable to pancreatic digestion, which could lead to enhanced bioavailability and in vivo bio-effectiveness.

[1161] Bobinaitė R et al. Phenolic compounds and antioxidant activities of raspberry cultivars 2012;132(3):1495-1501. Food Chem. 2012.

Food Chemistry study examining the phenolic compounds and antioxidant activities of raspberry cultivars.

[1163] Holton TR. The case for raspberry ketones in weight loss — a critical review 2017;18(2):237-249. Obes Rev. 2017.

Obesity Reviews critical review of the case for raspberry ketones in weight loss.

[1164] Strathearn KE et al. Neuroprotective effects of anthocyanin- and proanthocyanidin-rich extracts in cellular models of Parkinson's disease (mechanizmus, NEM humán RCT) 2014;1555:60-77. Brain Res. 2014. Link

This study assessed the neuroprotective effects of anthocyanin- and proanthocyanidin-rich botanical extracts in cellular (in vitro) models of Parkinson's disease. Extracts from blueberry, grape seed, hibiscus, blackcurrant, and Chinese mulberry suppressed rotenone-induced dopaminergic cell death, with anthocyanin/proanthocyanidin-rich extracts showing greater protection than those rich in other polyphenols. Blueberry and grape seed extracts rescued rotenone-induced defects in mitochondrial respiration. (A mechanistic study, NOT a human RCT.)

[1165] Cook MD et al. Blackcurrant extract and partially hydrolysed guar gum: a randomized controlled trial on gut microbiota in healthy adults 2024;16(8):1198. Nutrients. 2024.

Nutrients randomized controlled trial examining the effect of blackcurrant extract and partially hydrolysed guar gum on the gut microbiota in healthy adults.

[1166] Molan AL et al. Effects of blackcurrant-based functional beverage on colonic microbiota in healthy humans 2014;53(2):157-167. J Food Nutr Res. 2014.

Journal of Food and Nutrition Research study examining the effects of a blackcurrant-based functional beverage on the colonic microbiota in healthy humans.

[1167] Rodríguez-Daza MC et al. Berry-derived polyphenol bioactives: from microbiota modulation to clinical impact2021;8:689456. Front Nutr. Link

Frontiers in Nutrition review of berry-derived polyphenol bioactives, from microbiota modulation to clinical impact.

[1168] Slimestad R, Solheim H. Anthocyanins from black currants (Ribes nigrum L.)2002;50(11):3228-3231. J Agric Food Chem. 2002. Link

Fifteen anthocyanin structures are reported from an extract of black currant berries (Ribes nigrum L.). These are the 3-O-glucosides and the 3-O-rutinosides of pelargonidin, cyanidin, peonidin, delphinidin, petunidin, and malvidin, cyanidin 3-O-arabinoside, and the 3-O-(6' '-p-coumaroylglucoside)s of cyanidin and delphinidin. The anthocyanins were characterized by means of size exclusion chromatography, high-performance liquid chromatography, UV-visible spectroscopy, and electrospray mass spectrometry. The four main pigments (the 3-O-glucosides and the 3-O-rutinosides of delphinidin and cyanidin) made up >97\% of the total anthocyanin content. The minor pigments were enriched from the extract by successive partition against ethyl acetate and by gel fractionation. These chromatographic steps were successfully used to isolate the acylated anthocyanins from the ethyl acetate layer and to separate cyanidin 3-O-arabinoside from the mixture of anthocyanins.

[1169] Cyboran-Mikołajczyk S et al. The phenolic compounds and protective effects of blackcurrant pomace 2017;22(10):1647. Molecules. 2017.

Journal article by Cyboran-Mikołajczyk et al. (Molecules, 2017) examining the phenolic compounds and protective effects of blackcurrant pomace.

[1170] Watson AW et al. Acute supplementation with blackcurrant extracts modulates cognitive functioning and inhibits monoamine oxidase-B in healthy young adults2015;17:524-539. J Funct Foods. Link

A randomized, double-blind, placebo-controlled crossover study in 36 healthy young adults (18-35 years) assessing the acute effects of two blackcurrant extracts on cognitive performance, mood, and monoamine oxidase-B (MAO-B) inhibition. After consuming the extracts, attention and mood improved and mental fatigue was reduced; phenolic acids in the 'Blackadder' variety caused near-total (~96%) MAO-B inhibition. The data indicate that compounds other than anthocyanins may also be responsible for the observed in vivo MAO inhibition.

[1172] EU Commission. Health claim — vitamin C and immune function. Regulation (EC) No 1924/2006. . 1924.

EU Regulation (EC) No 1924/2006 on nutrition and health claims; cited here as the regulatory reference for the vitamin C and immune function health claim.

[1173] Williams G et al. Cranberries for preventing urinary tract infections — Cochrane review update2024;4:CD001321. Cochrane Database Syst Rev. Link

Updated Cochrane systematic review by Williams et al. (Cochrane Database Syst Rev, 2024) on cranberries for preventing urinary tract infections.

[1174] Howell AB et al. A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity2005;66(18):2281-2291. Phytochemistry. Link

Clinical, epidemiological and mechanistic studies support the role of cranberry (Vaccinium macrocarpon Ait.) in maintaining urinary tract health. Cranberry proanthocyanidins contain A-type linkages and have been associated with preventing adhesion of P-fimbriated uropathogenic Escherichia coli to uroepithelial cells. It is not known if the presence of the A-type linkage is a prerequisite for anti-adhesion activity. Other commercial sources of proanthocyanidins with all B-type linkages have not previously been screened for this activity. The goals of this study were to compare the in vitro anti-adhesion activity of A-linked proanthocyanidins from cranberry juice cocktail with the anti-adhesion activities of B-linked proanthocyanidins from commercial grape and apple juices, green tea and dark chocolate, and determine if anti-adhesion activity is detectable in human urine following consumption of single servings of each commercial food product. Structural heterogeneity and presence of the A-type linkage in cranberry proanthocyanidins was confirmed utilizing MALDI-TOF/MS and DI/ESI MS, as was the presence of all B-type linkages in the proanthocyanidins from the other commercial products.

[1175] Bekiares N et al. Effect of sweetened dried cranberry consumption on urinary proteome and fecal microbiome in healthy human subjects 2018;22(2):145-153. OMICS. 2018. Link

A prospective study in 10 healthy individuals consuming one serving (42 g) of sweetened dried cranberries daily for 2 weeks, examining the urinary proteome and fecal microbiome. Consumption resulted in changes to 22 urinary proteins (mass spectrometry) and increased the Firmicutes:Bacteroidetes ratio and the relative abundance of Akkermansia in feces. Given the small sample size, the findings are exploratory.

[1176] Sobota AE. Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections 1984;131(5):1013-1016. J Urol. 1984. Link

An early mechanistic study analyzing the antibacterial-adherence effect of cranberry juice on 77 clinical E. coli isolates. Cranberry juice inhibited adherence by at least 75% in over 60% of isolates; in mice, urine from animals given cranberry cocktail reduced E. coli adhesion to uroepithelial cells by about 80%, and 15 of 22 human subjects showed antiadherence activity in their urine. The author concludes that the purported benefit of cranberry juice may stem from its inhibition of bacterial adherence rather than urine acidification.

[1177] Hisano M et al. Cranberries and lower urinary tract infection prevention 2012;67(6):661-668. Clinics (Sao Paulo). 2012. Link

A review of the role of cranberries in preventing lower urinary tract infections (UTIs), summarizing in vitro studies and clinical findings. The authors note that cranberries inhibit E. coli adhesion to the urothelium and may be useful in treating/preventing urinary infections; clinical studies suggest a probable benefit as prophylaxis for female cystitis. As a review, it primarily synthesizes the existing evidence.

[1178] Aston JL et al. Interaction between warfarin and cranberry juice2006;26(9):1314-1319. Pharmacotherapy. Link

Warfarin is extensively used for anticoagulation to a target international normalized ratio of 2.0-3.0 for most indications or 2.5-3.5 for high-risk indications; however, many drugs and dietary supplements induce fluctuations in the international normalized ratio. Such fluctuations may lead to therapeutic failure or bleeding complications. Cranberry juice is increasingly used for the prevention and adjunctive treatment of urinary tract infections. The United Kingdom's Committee on Safety of Medicines has alerted clinicians to a potential interaction between warfarin and cranberry juice and has advised that patients avoid their concurrent use. Review and analysis of the literature revealed that ingestion of large volumes of cranberry juice destabilize warfarin therapy. Small amounts of juice are not expected to cause such an interaction.

[1179] Pappas E, Schaich KM. Phytochemicals of cranberries and cranberry products 2009;49(9):741-781. Crit Rev Food Sci Nutr. 2009.

Review article by Pappas and Schaich (Crit Rev Food Sci Nutr, 2009) on the phytochemicals of cranberries and cranberry products.

[1180] Liska DJ et al. Cranberries and urinary tract infections: how can the same evidence lead to conflicting advice? 2016;7(3):498-506. Adv Nutr. 2016. Link

A narrative/methodological review of how the same body of cranberry evidence for preventing recurrent urinary tract infections (UTIs) can yield conflicting recommendations. The authors argue the divergent conclusions stem mainly from differences in study design and meta-analytic methodology (heterogeneity in included trials, dose preparations, and outcomes).

[1181] FDA. Cranberry beverages and reduction of risk of recurrent urinary tract infections 2020;85. Federal Register. 2020.

U.S. FDA notice (Federal Register, 2020) on cranberry beverages and the reduction of risk of recurrent urinary tract infections.

[1182] Loo BM et al. Cardiovascular and metabolic effects of Aronia melanocarpa polyphenols: a double-blind RCT 2024;131(7):1198-1212. Br J Nutr. 2024.

Double-blind randomized controlled trial by Loo et al. (Br J Nutr, 2024) on the cardiovascular and metabolic effects of Aronia melanocarpa polyphenols.

[1183] Sidor A et al. Aronia melanocarpa L. — a comprehensive review on health-promoting effects 2024;64(15):4880-4901. Crit Rev Food Sci Nutr. 2024.

Comprehensive review by Sidor et al. (Crit Rev Food Sci Nutr, 2024) on the health-promoting effects of Aronia melanocarpa L.

[1184] Kulling SE, Rawel HM. Chokeberry (Aronia melanocarpa) — a review on the characteristic components and potential health effects2008;74(13):1625-1634. Planta Med. Link

The intention of this review is to contribute to a better understanding of the potentials of the nutritional contribution of ARONIA berries ( ARONIA MELANOCARPA). The paper gives a short background to their botanical classification and cultivation practice, going in detail to describe the chemical composition of the berries. The emphasis is laid thereby upon the phenolic constituents. The paper finally gives a short resume of their beneficial effects in biological systems IN VITRO, in animals, and in humans, thus underlining their medicinal potential.

[1185] Wu X et al. Concentrations of anthocyanins in common foods2006;54(11):4069-4075. J Agric Food Chem. Link

Article by Wu et al. (J Agric Food Chem, 2006) examining the concentrations of anthocyanins in common foods.

[1186] Park S et al. Effects of black chokeberry on the gut microbiota of healthy subjects 2023;15(8):1854. Nutrients. 2023.

Study by Park et al. (Nutrients, 2023) on the effects of black chokeberry on the gut microbiota of healthy subjects.

[1187] Sosnowska D et al. Bioactive components of chokeberry (Aronia melanocarpa) berries and their effects on gut microbiota 2022;88:104897. J Funct Foods. 2022.

Article by Sosnowska et al. (J Funct Foods, 2022) on the bioactive components of chokeberry (Aronia melanocarpa) berries and their effects on gut microbiota.

[1188] Borowska S, Brzóska MM. Chokeberries (Aronia melanocarpa) and their products as a possible means for the prevention and treatment of noncommunicable diseases2016;15(6):982-1017. Compr Rev Food Sci Food Saf. Link

Aronia melanocarpa berries (chokeberries) constitute a very rich source of numerous substances exerting a beneficial impact on health, including mainly polyphenols (proanthocyanidins, anthocyanins, flavonoids, and phenolic acids), possessing antioxidative, anti-inflammatory, antiviral, anticancer, antiatherosclerotic, hypotensive, antiplatelet, and antidiabetic properties. Thus, the consumption of products made from chokeberries is of vital importance for health maintenance and protection. Nowadays, due to the growing prevalence of noncommunicable diseases and ubiquitous human exposure to numerous man-made and naturally occurring toxic substances, some of which are dangerous even at low amounts, it is very important to look for effective means of health protection. An important role in this regard may be played by A. melanocarpa berries; however, up to now the attention of scientists, nutritionists, and health practitioners has been focused mainly on the effectiveness of chokeberry products in the prevention and treatment of noncommunicable diseases, while only little attention has been paid to the possibility of their use to counteract the adverse health effects of exposure to xenobiotics. That is why in this review article the main interest has been focused on the possibility of using chokeberries in the protection against unfavorable health effects caused by the action of substances to which humans may be exposed environmentally and/or occupationally. The available experimental data indicate that not only the fruit but also the leaves of A. melanocarpa and their products may be effective means for prevention and treatment of the effects of toxic action of some xenobiotics in humans; however, further studies on this subject are necessary.

[1189] Tian Y et al. High-pressure processing of chokeberry juice: bioactive compound retention and microbiological quality 2022;11(15):2280. Foods. 2022.

Study by Tian et al. (Foods, 2022) on high-pressure processing of chokeberry juice, addressing bioactive compound retention and microbiological quality.

[1190] . USDA Database for the Flavonoid Content of Selected Foods, Release 3.3.

USDA Database for the Flavonoid Content of Selected Foods (Release 3.3).

[1191] Rodriguez-Mateos A et al. Circulating anthocyanin metabolites mediate vascular benefits of blueberries: insights from randomized controlled trials. J Gerontol A Biol Sci Med Sci 2019;74(7):967–976. . 2019. Link

Potential health benefits of blueberries may be due to vascular effects of anthocyanins that predominantly circulate in blood as phenolic acid metabolites. We investigated which role blueberry anthocyanins and circulating metabolites play in mediating improvements in vascular function and explore potential mechanisms using metabolomics and nutrigenomics. Purified anthocyanins exerted a dose-dependent improvement of endothelial function in healthy humans, as measured by flow-mediated dilation. The effects were similar to those of wild blueberries containing similar amounts of anthocyanins, whereas control drinks containing fiber, minerals, or vitamins had no significant effect. Daily 1-month wild blueberry consumption increased flow-mediated dilation and lowered 24-hour ambulatory systolic blood pressure. Of the 63 anthocyanin plasma metabolites quantified, 14 and 21 correlated with acute and chronic flow-mediated dilation improvements, respectively.

[1192] Bowtell JL et al. Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation. Appl Physiol Nutr Metab 2017;42(7):773–779. . 2017. Link

Randomized, placebo-controlled trial in healthy older adults: 12 weeks of 30 mL/day anthocyanin-rich blueberry concentrate (~387 mg anthocyanidins) versus isoenergetic placebo. Supplementation increased brain perfusion and task-related activation in brain regions associated with cognitive (memory and executive) function.

[1193] Whyte AR et al. A randomized, double-blinded, placebo-controlled study of wild blueberry supplementation on cognition in 7–10 year-old children. Eur J Nutr 2016;55(6):2151–2162. . 2016. Link

PURPOSE: Previously, anthocyanin-rich blueberry treatments have shown positive effects on cognition in both animals and human adults. However, little research has considered whether these benefits transfer to children. Here we describe an acute time-course and dose-response investigation considering whether these cognitive benefits extend to children. METHODS: Using a double-blind cross-over design, on three occasions children (n = 21; 7-10 years) consumed placebo (vehicle) or blueberry drinks containing 15 or 30 g freeze-dried wild blueberry (WBB) powder. A cognitive battery including tests of verbal memory, word recognition, response interference, response inhibition and levels of processing was performed at baseline, and 1.15, 3 and 6 h following treatment. RESULTS: Significant WBB-related improvements included final immediate recall at 1.15 h, delayed word recognition sustained over each period, and accuracy on cognitively demanding incongruent trials in the interference task at 3 h.

[1194] Rocha DMUP et al. The role of dietary anthocyanins in glucose metabolism: a systematic review of randomized controlled trials. J Nutr Biochem 2020;76:108313. . 2020.

Systematic review of randomized controlled trials by Rocha et al. (J Nutr Biochem, 2020) on the role of dietary anthocyanins in glucose metabolism.

[1195] Krikorian R et al. Blueberry supplementation improves memory in older adults. J Agric Food Chem 2010;58(7):3996–4000. . 2010. Link

The prevalence of dementia is increasing with expansion of the older adult population. In the absence of effective therapy, preventive approaches are essential to address this public health problem. Blueberries contain polyphenolic compounds, most prominently anthocyanins, which have antioxidant and anti-inflammatory effects. In addition, anthocyanins have been associated with increased neuronal signaling in brain centers, mediating memory function as well as improved glucose disposal, benefits that would be expected to mitigate neurodegeneration. This study investigated the effects of daily consumption of wild blueberry juice in a sample of nine older adults with early memory changes. At 12 weeks, improved paired associate learning (p = 0.009) and word list recall (p = 0.04) were observed.

[1196] Lee S et al. Blueberry supplementation in midlife for dementia risk reduction: a randomized controlled trial. Nutrients 2022;14(8):1619. . 2022.

Randomized controlled trial by Lee et al. (Nutrients, 2022) on blueberry supplementation in midlife for dementia risk reduction.

[1197] Ozdal T et al. The reciprocal interactions between polyphenols and gut microbiota. Nutrients 2016;8(2):78. . 2016.

Review by Ozdal et al. (Nutrients, 2016) on the reciprocal interactions between polyphenols and gut microbiota.

[1198] Joseph JA, Shukitt-Hale B et al. Reversing the deleterious effects of aging on neuronal communication and behavior: beneficial properties of blueberries. J Neurosci 1999;19(18):8114–8121. . 1999.

Article by Joseph, Shukitt-Hale et al. (J Neurosci, 1999) on the beneficial properties of blueberries in relation to aging effects on neuronal communication and behavior.

[1199] Zhang Y, Neogi T, Chen C, Chaisson C, Hunter DJ, Choi HK Arthritis Rheum. 2012;64(12):4004–4011. Cherry consumption and decreased risk of recurrent gout attacks. 2012. Link

OBJECTIVE: To study the relationship between cherry intake and the risk of recurrent gout attacks among individuals with gout. METHODS: We conducted a case-crossover study to examine the associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed up online for 1 year. Participants were asked to provide the following information regarding gout attacks: the onset date of the gout attack, symptoms and signs, medications (including antigout medications), and exposure to potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression.

[1200] Pigeon WR, Carr M, Gorman C, Perlis ML J Med Food. 2010;13(3):579–583. Effects of a tart cherry juice beverage on the sleep of older adults with insomnia: a pilot study. 2010. Link

This study ascertained whether a proprietary tart cherry juice blend (CherryPharm, Inc., Geneva, NY, USA) associated with anecdotal reports of sleep enhancement improves subjective reports of insomnia compared to a placebo beverage. The pilot study used a randomized, double-blind, crossover design where each participant received both treatment and placebo for 2 weeks with an intervening 2-week washout period. Sleep continuity (sleep onset, wake after sleep onset, total sleep time, and sleep efficiency) was assessed by 2-week mean values from daily sleep diaries and disease severity by the Insomnia Severity Index in a cohort of 15 older adults with chronic insomnia who were otherwise healthy. The tart cherry juice beverage was associated with statistically significant pre- to post-treatment improvements on all sleep variables. When compared to placebo, the study beverage produced significant reductions in insomnia severity (minutes awake after sleep onset); no such improvements were observed for sleep latency, total sleep time, or sleep efficiency compared to placebo. Effect sizes were moderate and in some cases negligible.

[1201] Howatson G, Bell PG, Tallent J, Middleton B, McHugh MP, Ellis J Eur J Nutr. 2012;51(8):909–916. Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality. 2012. Link

BACKGROUND: Tart Montmorency cherries have been reported to contain high levels of phytochemicals including melatonin, a molecule critical in regulating the sleep-wake cycle in humans. PURPOSE: The aim of our investigation was to ascertain whether ingestion of a tart cherry juice concentrate would increase the urinary melatonin levels in healthy adults and improve sleep quality. METHODS: In a randomised, double-blind, placebo-controlled, crossover design, 20 volunteers consumed either a placebo or tart cherry juice concentrate for 7 days. Measures of sleep quality recorded by actigraphy and subjective sleep questionnaires were completed. Sequential urine samples over 48 h were collected and urinary 6-sulfatoxymelatonin (major metabolite of melatonin) determined; cosinor analysis was used to determine melatonin circadian rhythm (mesor, acrophase and amplitude). In addition, total urinary melatonin content was determined over the sampled period.

[1202] Bell PG, Walshe IH, Davison GW, Stevenson E, Howatson G Nutrients. 2014;6(2):829–843. Montmorency cherries reduce the oxidative stress and inflammatory responses to repeated days high-intensity stochastic cycling. 2014.

Study by Bell et al. (Nutrients, 2014) on whether Montmorency cherries reduce oxidative stress and inflammatory responses to repeated days of high-intensity stochastic cycling.

[1203] Mayta-Apaza AC, Pottgen E, De Bodt J, et al. J Nutr Biochem. 2018;59:160–172. Impact of tart cherries polyphenols on the human gut microbiota and phenolic metabolites in vitro and in vivo. 2018.

In vitro and in vivo study by Mayta-Apaza et al. (J Nutr Biochem, 2018) on the impact of tart cherry polyphenols on the human gut microbiota and phenolic metabolites.

[1204] Kelley DS, Adkins Y, Laugero KD Nutrients. 2018;10(3):368. A review of the health benefits of cherries. 2018.

Review by Kelley et al. (Nutrients, 2018) of the health benefits of cherries.

[1205] Schumacher HR Jr, Pullman-Mooar S, Gupta SR, et al. Osteoarthritis Cartilage. 2013;21(8):1035–1041. Randomized double-blind crossover study of the efficacy of a tart cherry juice blend in treatment of osteoarthritis. 2013.

Randomized double-blind crossover study by Schumacher et al. (Osteoarthritis Cartilage, 2013) on the efficacy of a tart cherry juice blend in the treatment of osteoarthritis.

[1206] Stacewicz-Sapuntzakis M Crit Rev Food Sci Nutr. 2013;53(12):1277–1302. Dried plums and their products: composition and health effects—an updated review. 2013. Link

This paper describes composition of dried plums and their products (prune juice and dried plum powder) with special attention to possibly bioactive compounds. Dried plums contain significant amounts of sorbitol, quinic acid, chlorogenic acids, vitamin K1, boron, copper, and potassium. Synergistic action of these and other compounds, which are also present in dried plums in less conspicuous amounts, may have beneficial health effects when dried plums are regularly consumed. Snacking on dried plums may increase satiety and reduce the subsequent intake of food, helping to control obesity, diabetes, and related cardiovascular diseases. Despite their sweet taste, dried plums do not cause large postprandial rise in blood glucose and insulin. Direct effects in the gastrointestinal tract include prevention of constipation and possibly colon cancer.

[1207] Gallaher CM, Gallaher DD Br J Nutr. 2009;101(2):233–239. Dried plums (prunes) reduce atherosclerosis lesion area in apolipoprotein E-deficient mice. 2009.

Animal study by Gallaher and Gallaher (Br J Nutr, 2009) on dried plums (prunes) reducing atherosclerosis lesion area in apolipoprotein E-deficient mice.

[1208] Yang JF, Yang CH, Liang MT, et al. J Food Sci. 2015;80(4):H712–H720. Chemical composition, antioxidant, and biological activities of plum (Prunus domestica) cultivar extracts. 2015.

Article by Yang et al. (J Food Sci, 2015) on the chemical composition, antioxidant, and biological activities of plum (Prunus domestica) cultivar extracts.

[1209] Igwe EO, Charlton KE Phytother Res. 2016;30(5):701–731. A systematic review on the health effects of plums (Prunus domestica and Prunus salicina). 2016. Link

Systematic review by Igwe and Charlton (Phytother Res, 2016) on the health effects of plums (Prunus domestica and Prunus salicina).

[1210] Hooshmand S, Arjmandi BH Ageing Res Rev. 2009;8(2):122–127. (összehasonlítás aszalt változattal)**. Viewpoint: dried plum, an emerging functional food that may effectively improve bone health. 2009.

Viewpoint article by Hooshmand and Arjmandi (Ageing Res Rev, 2009) on dried plum as an emerging functional food that may improve bone health.

[1211] Hooshmand S et al. Br J Nutr. 2011;106(6):923–930. Comparative effects of dried plum and dried apple on bone in postmenopausal women. 2011. Link

Aside from existing drug therapies, certain lifestyle and nutritional factors are known to reduce the risk of osteoporosis. Among the nutritional factors, dried plum or prunes (Prunus domestica L.) is the most effective fruit in both preventing and reversing bone loss. The objective of the present study was to examine the extent to which dried plum reverses bone loss in osteopenic postmenopausal women. We recruited 236 women, 1-10 years postmenopausal, not on hormone replacement therapy or any other prescribed medication known to influence bone metabolism. Qualified participants (n 160) were randomly assigned to one of the two treatment groups: dried plum (100 g/d) or dried apple (comparative control). Participants received 500 mg Ca plus 400 IU (10 μg) vitamin D daily.

[1212] Klimek-Szczykutowicz M, Szopa A, Ekiert H Plants. 2020;9(7):871. Chemical composition, traditional and professional use in medicine, application in environmental protection, position in food and cosmetics industries, and biotechnological studies of apricot. 2020.

Review by Klimek-Szczykutowicz et al. (Plants, 2020) on the chemical composition, traditional and professional medicinal use, and food and cosmetics applications of apricot.

[1213] Milazzo S, Horneber M Cochrane Database Syst Rev. 2015;(4):CD005476. Laetrile treatment for cancer. 2015. Link

Cochrane systematic review by Milazzo and Horneber (Cochrane Database Syst Rev, 2015) on laetrile treatment for cancer.

[1214] Bromley J, Hughes BG, Leong DC, Buckley NA Ann Pharmacother. 2005;39(9):1566–1569. Life-threatening interaction between complementary medicines: cyanide toxicity following ingestion of amygdalin and vitamin C. 2005.

Case report by Bromley et al. (Ann Pharmacother, 2005) on cyanide toxicity following ingestion of amygdalin and vitamin C as a life-threatening interaction between complementary medicines.

[1215] EFSA Panel on Contaminants in the Food Chain EFSA Journal. 2016;14(4):4424. Acute health risks related to the presence of cyanogenic glycosides in raw apricot kernels and products derived from raw apricot kernels. 2016. Link

Scientific opinion of the EFSA Panel on Contaminants in the Food Chain (EFSA Journal, 2016) on acute health risks related to cyanogenic glycosides in raw apricot kernels and derived products.

[1216] The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group N Engl J Med. 1994;330(15):1029–1035. The effect of vitamin E and beta carotene on the incidence of lung cancer. 1994.

Report by the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group (N Engl J Med, 1994) on the effect of vitamin E and beta carotene on the incidence of lung cancer.

[1217] Akin EB, Karabulut I, Topcu A Food Chem. 2008;107(2):939–948. Some compositional properties of main Malatya apricot (Prunus armeniaca L.) varieties. 2008.

Article by Akin et al. (Food Chem, 2008) on some compositional properties of the main Malatya apricot (Prunus armeniaca L.) varieties.

[1218] Noratto G et al. Identifying peach and plum polyphenols with chemopreventive potential against estrogen-independent breast cancer cells. J Agric Food Chem 2009;57(12):5219–5226. . 2009. Link

Our objective was to evaluate the cancer suppression activity of extracts from a commercial variety of yellow-fleshed peach 'Rich Lady' (RL) and a red-fleshed plum 'Black Splendor' (BS) and identify the phenolic fractions that may possess potential as chemopreventive and/or chemotherapeutic natural compounds. The peach RL extract effectively inhibited the proliferation of the estrogen-independent MDA-MB-435 breast cancer cell line. The concentration to inhibit 50\% of cell proliferation (IC(50)) was approximately 42 mg/L for this cell line compared to an IC(50) of approximately 130 and approximately 515 mg/L for the noncancerous breast cell line MCF-10A and the estrogen-dependent breast cancer cell line MCF-7, respectively. Similarly, BS extracts showed greater effects on MDA-MB-435 cells as compared to the other breast cancer or the normal breast cell lines. In general, BS extracts were less effective than RL extracts. Within all RL and BS fractions, fraction 3 (F3, flavonoids) and fraction 4 (F4, procyanidins) were more potent than fraction 1 (F1, phenolic acids) and fraction 2 (F2, anthocyanins) against the three cell lines.

[1219] Ranjbar A et al. Effects of fresh peach consumption on metabolic and oxidative stress markers in patients with metabolic syndrome: a randomized clinical trial. Phytother Res 2018;32(7):1379–1386. . 2018.

Randomized clinical trial by Ranjbar et al. (Phytother Res, 2018) on the effects of fresh peach consumption on metabolic and oxidative stress markers in patients with metabolic syndrome.

[1220] Olthof MR et al. Chlorogenic acid, quercetin-3-rutinoside and black tea phenols are extensively metabolized in humans. J Nutr 2003;133(6):1806–1814. . 2003. Link

Human metabolism study: about half of ingested chlorogenic acid and ~43% of black tea phenols were converted to hippuric acid, while quercetin-3-rutinoside was metabolized mainly to phenylacetic acid derivatives (e.g., 3-hydroxyphenylacetic acid). The authors conclude that colonic microflora convert most dietary phenols into simpler metabolites with lower antioxidant activity than the parent compounds.

[1221] Sugiura M et al. Dietary patterns of antioxidant vitamin and carotenoid intake associated with bone mineral density: findings from post-menopausal Japanese female subjects. Osteoporos Int 2011;22(1):143–152. . 2011. Link

Study in post-menopausal Japanese women examining the relationship between dietary intake of antioxidant vitamins and carotenoids and bone mineral density (BMD). Antioxidant carotenoids, especially β-cryptoxanthin and β-carotene, were inversely associated with the loss of radial BMD, suggesting higher carotenoid intake helps preserve bone density.

[1222] Lara MV et al. Peach (Prunus persica) fruit response to anoxia: reversible ripening delay and biochemical changes 2011;52(2):392–403. Plant Cell Physiol. 2011. Link

Postharvest physiology study: peaches (Prunus persica) were subjected to a 72 h anoxic (N2-atmosphere) treatment. The treatment effectively delayed ripening (preventing softening, color change, and ethylene production), inducing fermentative pathways and glycolysis; upon return to aerobic conditions the changes reversed — except acetaldehyde levels — with no post-anoxia injury.

[1223] Liu H et al. Health-promoting components of fruits and vegetables in the diet. Adv Nutr 2017;8(1):17S–28S. . 2017.

Review by Liu et al. (Adv Nutr, 2017) on the health-promoting components of fruits and vegetables in the diet.

[1224] Tomás-Barberán FA et al. HPLC-DAD-ESIMS analysis of phenolic compounds in nectarines, peaches, and plums. J Agric Food Chem 2001;49(10):4748–4760. . 2001. Link

Phenolic compounds of 25 peach, nectarine, and plum cultivars were analyzed and quantified by HPLC-DAD-ESIMS, identifying hydroxycinnamates, procyanidins, flavonols, and anthocyanins. Peel tissue contained higher phenolic amounts, with anthocyanins and flavonols located almost exclusively there; no clear trend in phenolic content with ripening was observed.

[1225] Kislev ME, Hartmann A, Bar-Yosef O Science. 2006;312(5778):1372–1374. Early domesticated fig in the Jordan Valley. 2006. Link

Article by Kislev et al. (Science, 2006) on early domesticated fig in the Jordan Valley.

[1226] Solomon A, Golubowicz S, Yablowicz Z, et al. J Agric Food Chem. 2006;54(20):7717–7723. Antioxidant activities and anthocyanin content of fresh fruits of common fig (Ficus carica L.). 2006. Link

Article by Solomon et al. (J Agric Food Chem, 2006) on the antioxidant activities and anthocyanin content of fresh fruits of common fig (Ficus carica L.).

[1227] Devaraj KB, Kumar PR, Prakash V Process Biochem. 2011;46(2):458–464. Comparison of activity and conformational changes of ficin during denaturation by urea and guanidine hydrochloride. 2011.

Article by Devaraj et al. (Process Biochem, 2011) comparing the activity and conformational changes of ficin during denaturation by urea and guanidine hydrochloride.

[1228] Hemmer W, Focke M, Götz M, Jarisch R Clin Exp Allergy. 2004;34(8):1251–1258. Sensitization to Ficus benjamina: relationship to natural rubber latex allergy and identification of foods implicated in the Ficus-fruit syndrome. 2004.

Article by Hemmer et al. (Clin Exp Allergy, 2004) on sensitization to Ficus benjamina, its relationship to natural rubber latex allergy, and foods implicated in the Ficus-fruit syndrome.

[1229] Mawa S, Husain K, Jantan I Evid Based Complement Alternat Med. 2013;2013:974256. Ficus carica L. (Moraceae): phytochemistry, traditional uses and biological activities. 2013. Link

Review article (Evid Based Complement Alternat Med) on the phytochemistry, traditional uses and biological activities of Ficus carica L. (Moraceae).

[1230] Veberic R, Colaric M, Stampar F Food Chem. 2008;106(1):153–157. Phenolic acids and flavonoids of fig fruit (Ficus carica L.) in the northern Mediterranean region. 2008.

Article by Veberic et al. (Food Chem, 2008) on the phenolic acids and flavonoids of fig fruit (Ficus carica L.) in the northern Mediterranean region.

[1231] Rathnavelu V et al. Potential role of bromelain in clinical and therapeutic applications. Biomed Rep 2016;5(3):283–288. . 2016. Link

Review article (Biomed Rep) on the potential clinical and therapeutic applications of bromelain.

[1232] Pavan R et al. Properties and therapeutic application of bromelain: a review. Biotechnol Res Int 2012;2012:976203. . 2012. Link

Review by Pavan et al. (Biotechnol Res Int, 2012) on the properties and therapeutic application of bromelain.

[1233] Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. J Ethnopharmacol 1988;22(2):191–203. . 1988. Link

A review of bromelain, the proteolytic enzyme complex of pineapple (Ananas comosus), and its clinical applications. The authors summarize bromelain's documented properties: inhibition of malignant cell growth, inhibition of platelet aggregation, fibrinolytic and anti-inflammatory action, and skin debridement, with therapeutic relevance to tumor growth, blood coagulation, inflammation, and burn wound treatment.

[1234] Hossain MA et al. Total phenolic content, antioxidative, antimicrobial activity and chemical composition of pineapple (Ananas comosus). Asian Pac J Trop Biomed 2015;5(8):596–600. . 2015.

Article by Hossain et al. (Asian Pac J Trop Biomed, 2015) on the total phenolic content, antioxidative and antimicrobial activity, and chemical composition of pineapple (Ananas comosus).

[1235] de Oliveira CV et al. Effects of pineapple juice consumption on satiety, glycemic response and gut microbiota markers. Food Funct 2017. . 2017.

Article by de Oliveira et al. (Food Funct, 2017) on the effects of pineapple juice consumption on satiety, glycemic response, and gut microbiota markers.

[1236] BfArM Kommission E Monograph. Bromelain. German Federal Institute for Drugs and Medical Devices.

Monograph on bromelain by the German Federal Institute for Drugs and Medical Devices (BfArM) Kommission E.

[1237] Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci 2001;58(9):1234–1245. . 2001. Link

Bromelain is a crude extract from the pineapple that contains, among other components, various closely related proteinases, demonstrating, in vitro and in vivo, antiedematous, antiinflammatory, antithrombotic and fibrinolytic activities. The active factors involved are biochemically characterized only in part. Due to its efficacy after oral administration, its safety and lack of undesired side effects, bromelain has earned growing acceptance and compliance among patients as a phytotherapeutical drug. A wide range of therapeutic benefits has been claimed for bromelain, such as reversible inhibition of platelet aggregation, angina pectoris, bronchitis, sinusitis, surgical traumas, thrombophlebitis, pyelonephritis and enhanced absorption of drugs, particularly of antibiotics. Biochemical experiments indicate that these pharmacological properties depend on the proteolytic activity only partly, suggesting the presence of nonprotein factors in bromelain. Recent results from preclinical and pharmacological studies recommend bromelain as an orally given drug for complementary tumor therapy: bromelain acts as an immunomodulator by raising the impaired immunocytotoxicity of monocytes against tumor cells from patients and by inducing the production of distinct cytokines such as tumor necrosis factor-a, interleukin (Il)-1beta, Il-6, and Il-8.

[1238] Asgary S et al. The effects of Diospyros kaki (Persimmon) on cardiovascular risk factors: a systematic review of clinical trials. Phytother Res 2019;33(7):1761–1773. . 2019.

Systematic review of clinical trials by Asgary et al. (Phytother Res, 2019) on the effects of Diospyros kaki (persimmon) on cardiovascular risk factors.

[1239] Gorinstein S et al. Influence of two cultivars of persimmon on bioactive compounds and antioxidant activity. J Agric Food Chem 2011;59(6):2706–2713. . 2011.

Article by Gorinstein et al. (J Agric Food Chem, 2011) on the influence of two persimmon cultivars on bioactive compounds and antioxidant activity.

[1240] Park YS et al. Bioactive compounds and antioxidant capacities of fresh persimmon cultivars. Food Chem 2008;107(2):640–648. . 2008.

Article by Park et al. (Food Chem, 2008) on the bioactive compounds and antioxidant capacities of fresh persimmon cultivars.

[1241] Sugiura M et al. Dietary patterns of antioxidant vitamin and carotenoid intake associated with bone mineral density. Osteoporos Int 2011;22(1):143–152. . 2011. Link

[1242] Mallavadhani UV et al. Pharmacology and chemotaxonomy of Diospyros. Phytochemistry 1998;49(4):901–951. . 1998. Link

A comprehensive review of the pharmacology and chemotaxonomy of the genus Diospyros (Ebenaceae). The authors document about 300 isolated and identified organic compounds; the genus is characterized by a large number of pentacyclic triterpenes and juglone-based 1,4-naphthoquinone metabolites that can serve as chemotaxonomic markers.

[1243] Butt MS et al. Persimmon (Diospyros kaki) fruit: hidden phytochemicals and health claims. EXCLI J 2015;14:542–561. . 2015. Link

Review article (EXCLI J) on the phytochemicals and health claims of persimmon (Diospyros kaki) fruit.

[1244] Iwasawa H et al. Anti-oxidant effects of kaki tannin in healthy volunteers. Biosci Biotechnol Biochem 2009;73(5):1071–1076. . 2009.

Study by Iwasawa et al. (Biosci Biotechnol Biochem, 2009) on the antioxidant effects of kaki tannin in healthy volunteers.

[1245] Muss C, Mosgoeller W, Endler T Neuro Endocrinol Lett. 2013;34(1):38–46. Papaya preparation (Caricol®) in digestive disorders. 2013. Link

Article by Muss et al. (Neuro Endocrinol Lett, 2013) on a papaya preparation (Caricol®) in digestive disorders.

[1246] Schweiggert RM, Kopec RE, Villalobos-Gutierrez MG, et al. Br J Nutr. 2014;111(3):490–498. Carotenoids are more bioavailable from papaya than from tomato and carrot in humans: a randomised cross-over study. 2014. Link

Randomised cross-over human study (Br J Nutr) showing that carotenoids are more bioavailable from papaya than from tomato and carrot in humans.

[1247] Aravind G, Bhowmik D, Duraivel S, Harish G J Med Plants Stud. 2013;1(1):7–15. Traditional and medicinal uses of Carica papaya. 2013.

Review by Aravind et al. (J Med Plants Stud, 2013) on the traditional and medicinal uses of Carica papaya.

[1248] Okeniyi JAO, Ogunlesi TA, Oyelami OA, Adeyemi LA J Med Food. 2007;10(1):194–196. Effectiveness of dried Carica papaya seeds against human intestinal parasitosis: a pilot study. 2007. Link

The tropical fruit Carica papaya and its seeds have proven antihelminthic and anti-amoebic activities. To determine the effectiveness of air-dried C. papaya seeds on human intestinal parasitosis, 60 asymptomatic Nigerian children with stool microscopic evidence of intestinal parasites received immediate doses (20 mL) of either an elixir composed with air-dried C. papaya seeds and honey (CPH) or honey alone (placebo) in two randomized treatment groups. Repeat stool microscopic examinations were conducted 7 days postintervention for intestinal parasites. Significantly more subjects given CPH elixir than those given honey had their stools cleared of parasites [23 of 30 (76.7\%) vs. five of 30 (16.7\%); z = 4.40, P = .0000109]. There were no harmful effects. The stool clearance rate for the various types of parasites encountered was between 71.4\% and 100\% following CPH elixir treatment compared with 0-15.4\% with honey.

[1249] Pavan R, Jain S, Shraddha, Kumar A Biotechnol Res Int. 2012;2012:976203. (comparative). Properties and therapeutic application of bromelain: a review. 2012. Link

Comparative review by Pavan et al. (Biotechnol Res Int, 2012) on the properties and therapeutic application of bromelain.

[1250] Krishna KL, Paridhavi M, Patel JA Nat Prod Rad. 2008;7(4):364–373. Review on nutritional, medicinal and pharmacological properties of papaya (Carica papaya Linn.). 2008.

Review by Krishna et al. (Nat Prod Rad, 2008) on the nutritional, medicinal, and pharmacological properties of papaya (Carica papaya Linn.).

[1251] Yogiraj V, Goyal PK, Chauhan CS, Goyal A, Vyas B Int J Herb Med. 2014;2(5):01–08. Carica papaya Linn: an overview. 2014.

Overview review by Yogiraj et al. (Int J Herb Med, 2014) on Carica papaya Linn.

[1252] Collins JK, Wu G, Perkins-Veazie P, et al. Nutrition. 2007;23(3):261–266. Watermelon consumption increases plasma arginine concentrations in adults. 2007. Link

Study in adults examining the link between watermelon consumption and plasma arginine concentrations (Nutrition).

[1253] Figueroa A, Sanchez-Gonzalez MA, Perkins-Veazie PM, Arjmandi BH Am J Hypertens. 2011;24(1):40–44. Effects of watermelon supplementation on aortic blood pressure and wave reflection in individuals with prehypertension: a pilot study. 2011. Link

BACKGROUND: Oral L-citrulline is efficiently converted to L-arginine, the precursor for endothelial nitric oxide (NO) synthesis. Oral L-arginine supplementation reduces brachial blood pressure (BP). We evaluated the effects of watermelon supplementation on aortic BP and arterial function in individuals with prehypertension. METHODS: Heart rate (HR), brachial systolic BP (bSBP), brachial pulse pressure (bPP), aortic SBP (aSBP), aortic PP (aPP), augmentation index (AIx), AIx adjusted for HR of 75 beats/min (AIx@75), amplitude of the first (P1) and second (P2) systolic peaks, reflection time (Tr), and carotid-femoral pulse wave velocity (PWV) were evaluated in the supine position in nine subjects (four men/five women, age 54 ± 3 years) with prehypertension (134/77 ± 5/3 mm Hg). Subjects were randomly assigned to 6 weeks of watermelon supplementation (L-citrulline/L arginine, 2.7 g/1.3 g/day) or placebo followed by a 4-week washout period and then crossover. RESULTS: There was a significant treatment effect (change in the value of watermelon minus placebo from baseline to 6 weeks) on bPP (-8 ± 3 mm Hg, P < 0.05), aSBP (-7 ± 2 mm Hg, P < 0.05), aPP (-6 ± 2 mm Hg, P < 0.01), AIx (-6 ± 3\%, P < 0.05), AIx@75 (-4 ± 2\%, P < 0.05), and P2 (-2 ± 1 mm Hg, P < 0.05).

[1254] Figueroa A, Sanchez-Gonzalez MA, Wong A, Arjmandi BH Am J Hypertens. 2012;25(6):640–643. Watermelon extract supplementation reduces ankle blood pressure and carotid augmentation index in obese adults with prehypertension or hypertension. 2012.

Clinical study on watermelon extract supplementation effects on ankle blood pressure and carotid augmentation index in obese adults with prehypertension or hypertension (Am J Hypertens).

[1255] Figueroa A, Wong A, Hooshmand S, Sanchez-Gonzalez MA Menopause. 2013;20(5):573–577. Effects of watermelon supplementation on arterial stiffness and wave reflection amplitude in postmenopausal women. 2013.

Study on watermelon supplementation effects on arterial stiffness and wave reflection amplitude in postmenopausal women (Menopause).

[1256] Cormio L, De Siati M, Lorusso F, et al. Urology. 2011;77(1):119–122. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. 2011.

Clinical study on oral L-citrulline supplementation and erection hardness in men with mild erectile dysfunction (Urology).

[1257] Edwards AJ, Vinyard BT, Wiley ER, et al. J Nutr. 2003;133(4):1043–1050. Consumption of watermelon juice increases plasma concentrations of lycopene and beta-carotene in humans. 2003. Link

Watermelon is a rich natural source of lycopene, a carotenoid of great interest because of its antioxidant capacity and potential health benefits. Assessment of bioavailability of lycopene from foods has been limited to tomato products, in which heat processing promotes lycopene bioavailability. We examined the bioavailability of lycopene from fresh-frozen watermelon juice in a 19-wk crossover study. Healthy, nonsmoking adults (36-69 y) completed three 3-wk treatment periods, each with a controlled, weight-maintenance diet. Treatment periods were preceded by "washout" periods of 2-4 wk during which lycopene-rich foods were restricted. All 23 subjects consumed the W-20 (20.1 mg/d lycopene, 2.5 mg/d beta-carotene from watermelon juice) and C-0 treatments (controlled diet, no juice).

[1258] Naz A, Butt MS, Sultan MT, Qayyum MM, Niaz RS EXCLI J. 2014;13:650–660. Watermelon lycopene and allied health claims. 2014.

Review on watermelon lycopene and associated health claims (EXCLI J).

[1259] Romero MJ, Platt DH, Caldwell RB, Caldwell RW Cardiovasc Drug Rev. 2006;24(3-4):275–290. Therapeutic use of citrulline in cardiovascular disease. 2006.

Review on the therapeutic use of citrulline in cardiovascular disease (Cardiovasc Drug Rev).

[1260] McCollum JT, Cronquist AB, Silk BJ, et al. N Engl J Med. 2013;369(10):944–953. Multistate outbreak of listeriosis associated with cantaloupe. 2013. Link

Report describing a multistate outbreak of listeriosis associated with cantaloupe (N Engl J Med).

[1261] Ren JS, Müller H, Salmenkivi K Asia Pac J Clin Nutr. 2008;17(S1):241–245. Carotenoid intake and risk of disease. 2008.

Study on carotenoid intake and risk of disease (Asia Pac J Clin Nutr).

[1262] Lester GE J Agric Food Chem. 2008;56(10):3694–3698. Antioxidant, sugar, mineral, and phytonutrient concentrations across edible fruit tissues of orange-fleshed honeydew melon (Cucumis melo L.). 2008.

Study on antioxidant, sugar, mineral, and phytonutrient concentrations across edible fruit tissues of orange-fleshed honeydew melon (Cucumis melo L.) (J Agric Food Chem).

[1263] Vinson JA, Su X, Zubik L, Bose P J Agric Food Chem. 2001;49(11):5315–5321. Phenol antioxidant quantity and quality in foods: fruits. 2001.

Study on phenol antioxidant quantity and quality in foods, specifically fruits (J Agric Food Chem).

[1264] Centers for Disease Control, Prevention MMWR Morb Mortal Wkly Rep. 2011;60(39):1357–1358. Multistate outbreak of listeriosis linked to whole cantaloupes from Jensen Farms, Colorado. 2011.

Report on a multistate outbreak of listeriosis linked to whole cantaloupes from Jensen Farms, Colorado (MMWR).

[1265] Manchali S, Murthy KNC, Vishnuvardana, Patil BS Plants. 2021;10(9):1755. Nutritional composition and health benefits of various botanical types of melon (Cucumis melo L.). 2021. Link

Review on the nutritional composition and health benefits of various botanical types of melon (Cucumis melo L.) (Plants).

[1266] Rolim PM, Fidelis GP, Padilha CE, et al. Food Sci Technol. 2018;38:233–243. Phenolic profile and antioxidant activity from peels and seeds of melon (Cucumis melo L. var. reticulatus). 2018.

Study on the phenolic profile and antioxidant activity from peels and seeds of melon (Cucumis melo L. var. reticulatus) (Food Sci Technol).

[1267] Ramos AT et al. Dietary fiber from passion fruit peel: extraction and characterization. Bioresour Technol 2007;98(13):2491–2497. . 2007.

Article on the extraction and characterization of dietary fiber from passion fruit peel (Bioresour Technol).

[1268] Setoguchi Y et al. Absorption and metabolism of piceatannol in rats and humans. J Agric Food Chem 2014;62(12):2541–2548. . 2014. Link

Study on the absorption and metabolism of piceatannol in rats and humans (J Agric Food Chem).

[1269] Matsui Y et al. Extract of passion fruit (Passiflora edulis) seed containing high amounts of piceatannol inhibits melanogenesis. Pharm Bull 2010;33(8):1417–1420. . 2010. Link

In vitro study on cultured human melanoma and fibroblast cells: an 80% ethanol extract of passion fruit (Passiflora edulis) seed (PF-S) inhibited melanogenesis and increased soluble collagen production. Piceatannol (3,4,3',5'-tetrahydroxy-trans-stilbene), present in large amounts in the seeds, was the major component responsible for the observed effects.

[1270] Janebro DI et al. Effect of passion fruit (Passiflora edulis) peel flour on metabolic indices of type 2 diabetic women. Rev Bras Farmacogn 2008;18(4):724–732. . 2008.

Study on the effect of passion fruit (Passiflora edulis) peel flour on metabolic indices of type 2 diabetic women (Rev Bras Farmacogn).

[1271] de Queiroz Mdo S et al. Effect of the yellow passion fruit peel flour on lipidic profile and hypertensive patients with type 2 diabetes mellitus. Nutr Hosp 2012;27(4):1130–1136. . 2012.

Study on the effect of yellow passion fruit peel flour on the lipid profile of hypertensive patients with type 2 diabetes mellitus (Nutr Hosp).

[1272] Carraro JC et al. Antioxidant capacity of passion fruit pulp and seed extracts. Food Chem 2020;308:125636. . 2020.

Study on the antioxidant capacity of passion fruit pulp and seed extracts (Food Chem).

[1273] He X, Luan F, Yang Y, Wang Z, Zhao Z, Fang J, et al. Front Pharmacol. 2020;11:617. Passiflora edulis: An insight into current researches on phytochemistry and pharmacology. 2020. Link

Review of current research on the phytochemistry and pharmacology of Passiflora edulis (Front Pharmacol).

[1274] Silva BM et al. Quince (Cydonia oblonga Miller) fruit (pulp, peel, and seed) and jam: antioxidant activity2004;52(15):4705–4712. J Agric Food Chem. Link

To study the antioxidant activity of quince fruit (pulp, peel, and seed) and jam, methanolic extracts were prepared. Each extract was fractionated into a phenolic fraction and an organic acid fraction and was analyzed by high-performance liquid chromatography (HPLC)/diode array detection and HPLC/UV, respectively. Antiradical activities of the extracts and fractions were evaluated by a microassay using 1,1'-diphenyl-2-picrylhydrazyl. The phenolic fraction always exhibited a stronger antioxidant activity than the whole methanolic extract. Organic acid extracts were always the weakest in terms of antiradical activity, which seems to indicate that the phenolic fraction gives a higher contribution for the antioxidant potential of quince fruit and jam. The evaluation of the antioxidant activity of methanolic extracts showed that peel extract was the one presenting the highest antioxidant capacity.

[1275] Wojdyło A, Teleszko M, Oszmiański J. Antioxidant property and storage stability of quince juice phenolic compounds 2014;152:261–270. Food Chem. 2014. Link

Eleven quince (Cydonia oblonga) cultivars were characterized for polyphenolic composition and antioxidant properties to provide data for industrial juice processing. The study examined the antioxidant properties and storage stability of phenolic compounds in quince juice.

[1276] Hemmati AA et al. Anti-inflammatory effect of leaf and seed mucilage. Avicenna J Phytomed 2019;9(2):177–185. Cydonia oblonga. 2019.

Study on the anti-inflammatory effect of Cydonia oblonga (quince) leaf and seed mucilage (Avicenna J Phytomed).

[1277] Larsen N et al. Effect of potato fiber on survival of Lactobacillus species at simulated gastric conditions and composition of the gut microbiota in vitro 2019;125:108644. Food Res Int. 2019. Link

In vitro study examining the effect of potato fiber on the survival of Lactobacillus species under simulated gastric conditions and on gut microbiota composition. Results indicate that potato fiber can improve survival of probiotic Lactobacillus strains under gastric conditions, in a strain-dependent manner.

[1279] Bang SJ et al. The influence of in vitro pectin fermentation on the human fecal microbiome 2018;8(1):98. AMB Express. 2018.

Study on the influence of in vitro pectin fermentation on the human fecal microbiome (AMB Express).

[1280] Stalmach A et al. Metabolite profiling of hydroxycinnamate derivatives in plasma and urine after the ingestion of coffee 2009;37(8):1749–1758. Drug Metab Dispos. 2009. Link

Human study: participants consumed coffee containing 412 µmol of chlorogenic acids, and plasma and urine were analyzed by HPLC-MS over 0-24 h. Some components peaked in plasma within 1 h (small-intestinal absorption), whereas dihydroferulic acid and its sulfates peaked after >4 h (large intestine). Urinary dihydrocaffeic acid-3-O-sulfate and feruloylglycine were identified as sensitive biomarkers of coffee consumption.

[1281] Kashyap D et al. Ursolic acid (UA): a metabolite with promising therapeutic potential 2016;146:201–213. Life Sci. 2016. Link

A review of the therapeutic potential of ursolic acid (UA). UA is a pentacyclic triterpenoid commonly found in medicinal herbs and plants, with multiple intracellular and extracellular targets, playing roles in apoptosis, metastasis, angiogenesis, and inflammatory processes.

[1283] Asai A et al. Inhibitory effect of mulberry leaf extract on postprandial hyperglycemia in normal and diabetic subjects2011;2(4):318–323. J Diabetes Investig. Link

Human study (J Diabetes Investig) on the inhibitory effect of mulberry leaf extract on postprandial hyperglycemia in normal and diabetic subjects.

[1284] Mudra M et al. Influence of mulberry leaf extract on the blood glucose and breath hydrogen response to ingestion of 75 g sucrose by type 2 diabetic and control subjects2007;30(5):1272–1274. Diabetes Care. Link

Study on the influence of mulberry leaf extract on the blood glucose and breath hydrogen response to ingestion of 75 g sucrose by type 2 diabetic and control subjects (Diabetes Care).

[1285] Hu XQ et al. Hypoglycemic effect of L. leaves and its quality control. Mini Rev Med Chem 2013;13(5):717–728. Morus alba. 2013.

Review on the hypoglycemic effect of Morus alba (mulberry) leaves and its quality control (Mini Rev Med Chem).

[1286] Sánchez-Salcedo EM et al. Phytochemical evaluation of white (Morus alba L.) and black (Morus nigra L.) mulberry fruits, a starting point for the assessment of their beneficial properties 2015;12:399–408. J Funct Foods. 2015. Link

Phenolic composition, antioxidant activity, and mineral content of white (Morus alba) and black (Morus nigra) mulberry fruits grown in Spain were evaluated. Black mulberry clones showed higher antioxidant activity and phenolic content than white ones (with notable intra-species variability); M. nigra inhibited pancreatic α-amylase and lipase.

[1287] de Ferrars RM et al. The pharmacokinetics of anthocyanins and their metabolites in humans 2014;171(13):3268–3282. Br J Pharmacol. 2014.

Study on the pharmacokinetics of anthocyanins and their metabolites in humans (Br J Pharmacol).

[1288] Khan N et al. Anthocyanins improve endothelial function: a systematic review of human studies 2014;58(5):951–963. Mol Nutr Food Res. 2014.

Systematic review of human studies on anthocyanins improving endothelial function (Mol Nutr Food Res).

[1289] Tomás-Barberán FA, Selma MV, Espín JC. Interactions of gut microbiota with dietary polyphenols and consequences to human health 2016;19(6):471–476. Curr Opin Clin Nutr Metab Care. 2016. Link

A review of the interactions between gut microbiota and dietary polyphenols and their consequences for human health. The authors emphasize that polyphenol bioavailability is low and that gut microbiota convert them into simpler, active, and bioavailable metabolites; because microbiota differ between individuals, this interindividual variability is a moderating factor in clinical trials.

[1290] Yang X et al. Mulberry leaf polysaccharides and their potential health benefits 2017;174:1175–1184. Carbohydr Polym. 2017.

Review on mulberry leaf polysaccharides and their potential health benefits (Carbohydr Polym).

[1292] Pantelidis GE et al. Antioxidant capacity, phenol, anthocyanin and ascorbic acid contents in raspberries, blackberries, red currants, gooseberries and Cornelian cherries2007;102(3):777–783. Food Chem. Link

Study on antioxidant capacity and phenol, anthocyanin and ascorbic acid contents in raspberries, blackberries, red currants, gooseberries and Cornelian cherries (Food Chem).

[1293] Mikulic-Petkovsek M et al. Composition of sugars, organic acids, and total phenolics in 25 wild or cultivated berry species2012;77(10):C1064–C1070. J Food Sci. Link

UNLABELLED: Sugars, organic acids, and total phenolic content in fruit of 25 wild and cultivated berry species were identified and quantified with high-performance liquid chromatograph. The composition of sugars, organic acids, and total phenolic compounds in various species of Vaccinium, Rubus, Ribes, and Fragaria genus was evaluated. Additonally, total phenolics of less known berry species of the Morus, Amelanchier, Sorbus, Sambucus, Rosa, Lycium, Actinidia, and Aronia genus were determined in wild growing as well as in cultivated fruits. Significant differences in the concentration of sugars and organic acids were detected among the berry species. Glucose and fructose were the most abundant sugars in berry fruits and the major organic acids were malic and citric acid. However, in kiwi fruit, sucrose represented as much as 71.9\% of total sugars.

[1294] Edwards RL et al. Quercetin reduces blood pressure in hypertensive subjects2007;137(11):2405–2411. J Nutr. Link

Epidemiological studies report that quercetin, an antioxidant flavonol found in apples, berries, and onions, is associated with reduced risk of coronary heart disease and stroke. Quercetin supplementation also reduces blood pressure in hypertensive rodents. The efficacy of quercetin supplementation to lower blood pressure in hypertensive humans has never been evaluated. We tested the hypothesis that quercetin supplementation reduces blood pressure in hypertensive patients. We then determined whether the antihypertensive effect of quercetin is associated with reductions in systemic oxidant stress. Men and women with prehypertension (n = 19) and stage 1 hypertension (n = 22) were enrolled in a randomized, double-blind, placebo-controlled, crossover study to test the efficacy of 730 mg quercetin/d for 28 d vs. placebo.

[1295] Larsen N et al. Effect of potato fiber on survival of Lactobacillus species at simulated gastric conditions and composition of the gut microbiota in vitro2019;125:108644. Food Res Int. Link

Potato fiber is a side product in starch manufacturing rich in dietary fibers such as pectin, cellulose, hemicellulose and resistant starch. So far, the beneficial properties of potato fiber have been poorly characterized. This study investigated the effect of FiberBind 400, a commercial potato fiber product, on survival of probiotic Lactobacillus strains at simulated gastric conditions and on the composition and metabolic activity of the gut microbiota, using the TIM-2 colon model. Resistant starch and native starch from potato were used as reference substrates. FiberBind 400 had an ability to improve survival of the four tested strains, Lactobacillus fermentum PCC®, L. rhamnosus LGG®, L. reuteri RC-14® and L. paracasei F-19® in a strain-dependent way. The highest effect was observed for L. fermentum PCC® and L. rhamnosus LGG®.

[1298] de Ferrars RM et al. The pharmacokinetics of anthocyanins and their metabolites in humans2014;171(13):3268–3282. Br J Pharmacol. Link

BACKGROUND AND PURPOSE: Anthocyanins are phytochemicals with reported vasoactive bioactivity. However, given their instability at neutral pH, they are presumed to undergo significant degradation and subsequent biotransformation. The aim of the present study was to establish the pharmacokinetics of the metabolites of cyanidin-3-glucoside (C3G), a widely consumed dietary phytochemical with potential cardioprotective properties. EXPERIMENTAL APPROACH: A 500 mg oral bolus dose of 6,8,10,3',5'-(13)C5-C3G was fed to eight healthy male participants, followed by a 48 h collection (0, 0.5, 1, 2, 4, 6, 24, 48 h) of blood, urine and faecal samples. Samples were analysed by HPLC-ESI-MS/MS with elimination kinetics established using non-compartmental pharmacokinetic modelling. KEY RESULTS: Seventeen (13)C-labelled compounds were identified in the serum, including (13)C5-C3G, its degradation products, protocatechuic acid (PCA) and phloroglucinaldehyde (PGA), 13 metabolites of PCA and 1 metabolite derived from PGA.

[1301] EFSA Panel on Dietetic Products Nutrition, Allergies. Scientific Opinion on the substantiation of a health claim related to dried plums (Prunus domestica L.) and contribution to normal bowel function2012;10(6):2712. EFSA Journal. Link

EFSA scientific opinion on the substantiation of a health claim related to dried plums (Prunus domestica L.) and contribution to normal bowel function (EFSA Journal).

[1302] Attaluri A et al. Randomised clinical trial: dried plums (prunes) vs. psyllium for constipation2011;33(7):822-828. Aliment Pharmacol Ther. Link

BACKGROUND: Treatment of chronic constipation remains challenging with 50\% of patients dissatisfied with current therapy. There is an unmet need for natural and safe alternatives. Dried plums (prunes) have been used traditionally for constipation but their efficacy is not known. Aim To assess and compare the effects of dried plums and psyllium in patients with chronic constipation. METHODS: Subjects were enrolled in an 8-week, single-blind, randomised cross-over study. Subjects received either dried plums (50 g b.d., fibre=6 gm/day) or psyllium (11 g b.d., fibre=6 gm/day) for 3 weeks each, in a crossover trial with a 1-week washout period.

[1303] Lever E et al. Systematic review: the effect of prunes on gastrointestinal function2014;40(7):750-758. Aliment Pharmacol Ther. Link

BACKGROUND: Prunes (dried plums) are high in fibre and are perceived to promote healthy gastrointestinal (GI) function. AIM: To assess the effect of prunes on GI function through a systematic review of randomised controlled trials (RCTs). METHODS: Sixteen electronic databases were searched, a hand search was performed and key opinion leaders were contacted. RCTs investigating the effect of prunes on GI function were included. Two reviewers independently screened relevant articles, extracted data and assessed risk of bias. RESULTS: Four trials met the inclusion criteria, one in constipation and three in non-constipated subjects.

[1304] Hooshmand S et al. Prunes preserve hip bone mineral density in a 12-month randomized controlled trial in postmenopausal women2022;116(4):897-910. Am J Clin Nutr. Link

BACKGROUND: Dietary consumption of prunes has favorable impacts on bone health, but more research is necessary to improve upon study designs and refine our understandings. OBJECTIVES: We evaluated the effects of prunes (50 g or 100 g/d) on bone mineral density (BMD) in postmenopausal women during a 12-mo dietary intervention. Secondary outcomes include effects on bone biomarkers. METHODS: The single-center, parallel-arm 12-mo randomized controlled trial tested the effects of 50 g and 100 g prunes compared with a control group on BMD (every 6 mo) and bone biomarkers in postmenopausal women. RESULTS: In total, 235 women (age 62.1 ± 5.0 y) were randomly allocated into control (n = 78), 50-g prune (n = 79), or 100-g prune (n = 78) groups. Compliance was 90.2 ± 1.8\% and 87.1 ± 2.1\% in the 50-g and 100-g prune groups.

[1305] Damani JJ et al. Microbiome-mediated changes in prune (dried plum) consumption — a randomized trial 2022;152(9):2107-2116. J Nutr. 2022.

Randomized trial on microbiome-mediated changes with prune (dried plum) consumption (J Nutr).

[1306] Stacewicz-Sapuntzakis M. Dried plums and their products: composition and health effects2013;53(12):1277-1302. Crit Rev Food Sci Nutr. Link

[1307] California Prune Board. Health and nutrition research summary. 2023. . 2023. Link

Health and nutrition research summary from the California Prune Board.

[1309] USDA FoodData Central. Plums, dried (prunes), uncooked. Link

USDA FoodData Central data entry for uncooked dried plums (prunes).

[1310] Eid N et al. The impact of date palm fruits and their component polyphenols, on gut microbial ecology, bacterial metabolites and colon cancer cell proliferation2014;3:e46. J Nutr Sci. Link

The fruit of the date palm (Phoenix dactylifera L.) is a rich source of dietary fibre and polyphenols. We have investigated gut bacterial changes induced by the whole date fruit extract (digested date extract; DDE) and its polyphenol-rich extract (date polyphenol extract; DPE) using faecal, pH-controlled, mixed batch cultures mimicking the distal part of the human large intestine, and utilising an array of microbial group-specific 16S rRNA oligonucleotide probes. Fluorescence microscopic enumeration indicated that there was a significant increase in the growth of bifidobacteria in response to both treatments, whilst whole dates also increased bacteroides at 24 h and the total bacterial counts at later fermentation time points when compared with DPE alone. Bacterial metabolism of whole date fruit led to the production of SCFA, with acetate significantly increasing following bacterial incubation with DDE. In addition, the production of flavonoid aglycones (myricetin, luteolin, quercetin and apigenin) and the anthocyanidin petunidin in less than 1 h was also observed. Lastly, the potential of DDE, DPE and metabolites to inhibit Caco-2 cell growth was investigated, indicating that both were capable of potentially acting as antiproliferative agents in vitro, following a 48 h exposure.

[1311] Alkaabi JM et al. Glycemic indices of five varieties of dates in healthy and diabetic subjects2011;10:59. Nutr J. Link

BACKGROUND: This study was designed to determine the glycemic indices of five commonly used varieties of dates in healthy subjects and their effects on postprandial glucose excursions in individuals with type 2 diabetes mellitus. METHODS: Composition analysis was carried out for five types of dates (Tamer stage). The weights of the flesh of the dates equivalent to 50 g of available carbohydrates were calculated. The study subjects were thirteen healthy volunteers with a mean (± SD) age of 40.2 ± 6.7 years and ten participants with type 2 diabetes mellitus (controlled on lifestyle measures and/or metformin) with a mean HbA1c (± SD) of 6.6 ± (0.7\%) and a mean age (± SD) of 40.8 ± 5.7 years. Each subject was tested on eight separate days with 50 g of glucose (on 3 occasions) and 50 g equivalent of available carbohydrates from the 5 varieties of date (each on one occasion). Capillary glucose was measured in the healthy subjects at 0, 15, 30, 45, 60, 90 and 120 min and for the diabetics at 0, 30, 60, 90, 120, 150 and 180 min.

[1312] Al-Kuran O et al. The effect of late pregnancy consumption of date fruit on labour and delivery2011;31(1):29-31. J Obstet Gynaecol. Link

We set out to investigate the effect of date fruit (Phoenix dactylifera) consumption on labour parameters and delivery outcomes. Between 1 February 2007 and 31 January 2008 at Jordan University of Science and Technology, a prospective study was carried out on 69 women who consumed six date fruits per day for 4 weeks prior to their estimated date of delivery, compared with 45 women who consumed none. There was no significant difference in gestational age, age and parity between the two groups. The women who consumed date fruit had significantly higher mean cervical dilatation upon admission compared with the non-date fruit consumers (3.52 cm vs 2.02 cm, p < 0.0005), and a significantly higher proportion of intact membranes (83\% vs 60\%, p = 0.007). Spontaneous labour occurred in 96\% of those who consumed dates, compared with 79\% women in the non-date fruit consumers (p = 0.024). Use of prostin/oxytocin was significantly lower in women who consumed dates (28\%), compared with the non-date fruit consumers (47\%) (p = 0.036).

[1313] Rahmani AH et al. Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases2014;7(3):483-491. Int J Clin Exp Med. Link

The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect.

[1314] Vayalil PK. Date fruits (Phoenix dactylifera Linn): an emerging medicinal food2012;52(3):249-271. Crit Rev Food Sci Nutr. Link

Date palm is one of the oldest trees cultivated by man. In the folk-lore, date fruits have been ascribed to have many medicinal properties when consumed either alone or in combination with other herbs. Although, fruit of the date palm served as the staple food for millions of people around the world for several centuries, studies on the health benefits are inadequate and hardly recognized as a healthy food by the health professionals and the public. In recent years, an explosion of interest in the numerous health benefits of dates had led to many in vitro and animal studies as well as the identification and quantification of various classes of phytochemicals. On the basis of available documentation in the literature on the nutritional and phytochemical composition, it is apparent that the date fruits are highly nutritious and may have several potential health benefits. Although dates are sugar-packed, many date varieties are low GI diet and refutes the dogma that dates are similar to candies and regular consumption would develop chronic diseases.

[1315] Sirisena S et al. The emerging Australian date palm industry: date fruit composition 2015;4(2):134-149. Foods. 2015.

Article on the emerging Australian date palm industry, focusing on date fruit composition (Foods).

[1316] Mrabet A et al. Date palm fruits as a potential source of functional dietary fiber: a review 2019;25(1):1-10. Food Sci Technol Res. 2019.

Review of date palm fruits as a potential source of functional dietary fiber (Food Sci Technol Res).

[1318] USDA FoodData Central. Dates, medjool. Link

USDA FoodData Central data entry for medjool dates.

[1319] Spiller GA et al. Effect of daily raisin consumption on gastrointestinal transit time in healthy adults2003;22(suppl). J Am Coll Nutr. Link

The effect of increasing doses of sun-dried raisins (SDR) on intestinal transit time (TT), fecal weight (FW), and fecal bile acids (FBA) was investigated in 16 healthy adults (6 men and 10 women). In three cycles of 2 weeks each, subjects consumed 84, 126, or 168 g/day of SDR. Four-day fecal collections were performed during the second week of each cycle, and TT, FW, and FBA were measured. FW (mean +/- SEM), increased from 168 +/- 14 g/day without raisins (cycle 1), with a TT of 54 +/- 6 hours, to 200 +/- 24 g/day with 168 g/day raisins (cycle 4), with a TT of 42 +/- 6 hours. Intermediate increases in FW and decreases in TT were observed for cycles 2 and 3. A physiologically meaningful decrease in TT (less than 2 days), to 44 +/- 6 hours, was reached at cycle 2 (not statistically significant).

[1320] Mandalari G et al. Faecal microbiota response to raisin and grape consumption: a 14-day human intervention 2010;103(11):1684-1689. Br J Nutr. 2010.

14-day human intervention study on the faecal microbiota response to raisin and grape consumption (Br J Nutr).

[1321] Patel BP et al. Effect of raisin consumption on blood pressure: a meta-analysis 2011;123(5):131-141. Postgrad Med. 2011.

Meta-analysis on the effect of raisin consumption on blood pressure (Postgrad Med).

[1322] Wu CD, Mao Z et al. Effects of raisins on caries-related microflora 2008;69(7):1573-1581. Phytochemistry. 2008.

Study on the effects of raisins on caries-related microflora (Phytochemistry).

[1323] Williamson G, Carughi A. Polyphenol content and health benefits of raisins2010;30(8):511-519. Nutr Res. Link

The health benefits of grapes and wine have been studied and publicized extensively, but dried grapes (raisins, including "sultanas" and "currants") have received comparatively little attention. The purpose of the review was to summarize the polyphenol, phenolic acid, and tannin (PPT) composition of raisins; predict the likely bioavailability of the component PPT; and summarize the results of human intervention studies involving raisins. The most abundant PPTs are the flavonols, quercetin and kaempferol, and the phenolic acids, caftaric and coutaric acid. On a wet weight basis, some PPTs, such as protocatechuic and oxidized cinnamic acids, are present at a higher level in raisins compared to grapes. In human intervention studies, raisins can lower the postprandial insulin response, modulate sugar absorption (glycemic index), affect certain oxidative biomarkers, and promote satiety via leptin and ghrelin. However, only limited numbers of studies have been performed, and it is not clear to what extent the PPT component is responsible for any effects.

[1324] Kaminskas A et al. Sun-dried raisin polyphenol profile and antioxidant activity 2022;11(2):195. Foods. 2022.

Study on the polyphenol profile and antioxidant activity of sun-dried raisins (Foods).

[1325] Anderson JW, Waters AR. Raisin consumption by humans: effects on glycemia and insulinemia2013;78(suppl):A11-A17. J Food Sci. Link

Raisins are widely recommended as good foods and preferred snacks because of their nutrient content. They are rich in dietary fiber, potassium, and many health-promoting phytonutrients and antioxidants. Raisins have a high dietary fiber score. Laboratory studies document that raisins rank in the upper quartile of foods for antioxidant content. Clinical research related to the potential health benefits of raisins has intensified over the past 10 y. Much of this research has focused on blood glucose and insulin responses to raisins compared to other foods or snacks.

[1327] Pasiakos SM et al. Sun-dried raisins: a dietary intervention to support cardiometabolic health 2021;12(3):1110-1124. Adv Nutr. 2021.

Review of sun-dried raisins as a dietary intervention to support cardiometabolic health (Adv Nutr).

[1328] Cohen HA et al. Effect of honey on nocturnal cough and sleep quality: a double-blind, randomized, placebo-controlled study2012;130(3):465-471. Pediatrics. Link

OBJECTIVES: To compare the effects of a single nocturnal dose of 3 honey products (eucalyptus honey, citrus honey, or labiatae honey) to placebo (silan date extract) on nocturnal cough and difficulty sleeping associated with childhood upper respiratory tract infections (URIs). METHODS: A survey was administered to parents on 2 consecutive days, first on the day of presentation, when no medication had been given the previous evening, and the following day, when the study preparation was given before bedtime, based on a double-blind randomization plan. Participants included 300 children aged 1 to 5 years with URIs, nocturnal cough, and illness duration of ≤ 7 days from 6 general pediatric community clinics. Eligible children received a single dose of 10 g of eucalyptus honey, citrus honey, labiatae honey, or placebo administered 30 minutes before bedtime. Main outcome measures were cough frequency, cough severity, bothersome nature of cough, and child and parent sleep quality. RESULTS: In all 3 honey products and the placebo group, there was a significant improvement from the night before treatment to the night of treatment.

[1329] Oduwole O et al. Honey for acute cough in children2018;4:CD007094. Cochrane Database Syst Rev. Link

BACKGROUND: Cough causes concern for parents and is a major cause of outpatient visits. Cough can impact quality of life, cause anxiety, and affect sleep in children and their parents. Honey has been used to alleviate cough symptoms. This is an update of reviews previously published in 2014, 2012, and 2010. OBJECTIVES: To evaluate the effectiveness of honey for acute cough in children in ambulatory settings. SEARCH METHODS: We searched CENTRAL (2018, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (2014 to 8 February 2018), Embase (2014 to 8 February 2018), CINAHL (2014 to 8 February 2018), EBSCO (2014 to 8 February 2018), Web of Science (2014 to 8 February 2018), and LILACS (2014 to 8 February 2018).

[1330] Münstedt K et al. Effects of basswood honey, honey with royal jelly, and honey on the level of glycemia in patients with type 2 diabetes 2009;12(5):1089-1093. J Med Food. 2009.

Study on the effects of basswood honey, honey with royal jelly, and honey on the level of glycemia in patients with type 2 diabetes (J Med Food).

[1331] Cianciosi D et al. Phenolic compounds in honey and their associated health benefits: a review2018;23(9):2322. Molecules. Link

Honey is a natural substance appreciated for its therapeutic abilities since ancient times. Its content in flavonoids and phenolic acids plays a key role on human health, thanks to the high antioxidant and anti-inflammatory properties that they exert. Honey possesses antimicrobial capacity and anticancer activity against different types of tumors, acting on different molecular pathways that are involved on cellular proliferation. In addition, an antidiabetic activity has also been highlighted, with the reduction of glucose, fructosamine, and glycosylated hemoglobin serum concentration. Honey exerts also a protective effect in the cardiovascular system, where it mainly prevents the oxidation of low-density lipoproteins, in the nervous system, in the respiratory system against asthma and bacterial infections, and in the gastrointestinal system. A beneficial effect of honey can also be demonstrated in athletes.

[1332] Molan PC. The antibacterial activity of honey: Manuka factor and methylglyoxal 2008;89(2):26-29. Bee World. 2008.

Article on the antibacterial activity of honey, focusing on the Manuka factor and methylglyoxal (Bee World).

[1333] CDC. Infant botulism — honey advisory2018;67(34). Morbidity and Mortality Weekly Report. Link

CDC infant botulism honey advisory (MMWR).

[1334] Saarinen K et al. Birch pollen honey for birch pollen allergy: a randomized controlled pilot study2011;155(2):160-166. Int Arch Allergy Immunol. Link

BACKGROUND: Only a few randomized controlled trials have been carried out to evaluate various complementary treatments for allergic disorders. This study assessed the effects of the preseasonal use of birch pollen honey (BPH; birch pollen added to honey) or regular honey (RH) on symptoms and medication during birch pollen season. METHODS: Forty-four patients (59\% female, mean age 33 years) with physician-diagnosed birch pollen allergy consumed either BPH or RH daily in incremental amounts from November 2008 to March 2009. Seventeen patients (53\% female, mean age 36 years) on their usual allergy medication served as the control group. From April to May, patients recorded daily rhinoconjunctival and other symptoms and their use of medication. Fifty patients completed the study.

[1335] Mohamed N et al. Yoghurt and honey synbiotic: a randomized trial on Bifidobacterium animalis enrichment 2024;16(6):812. Nutrients. 2024.

Randomized trial on a yoghurt and honey synbiotic regarding Bifidobacterium animalis enrichment (Nutrients).

[1337] Dai X et al. Consuming Lentinula edodes (shiitake) mushrooms daily improves human immunity: a randomized dietary intervention in healthy young adults2015;34(6):478-487. J Am Coll Nutr. Link

BACKGROUND: Mushrooms are widely cited for their medicinal qualities, yet very few human intervention studies have been done using contemporary guidelines. OBJECTIVE: The aim of this study was to determine whether consumption of whole, dried Lentinula edodes (shiitake) mushrooms could improve human immune function. Primary objectives were to ascertain whether L. edodes consumption would improve γδ-T cell proliferation and activation responses, quantify a dose response, and elicit cytokine secretion patterns. Secondary objectives included determining changes in natural killer T (NK-T) cell proliferation and activation, secretory immunoglobulin A (sIgA) in saliva, and C-reactive protein (CRP) in serum. DESIGN: Fifty-two healthy males and females, aged 21-41 years, participated in a 4-week parallel group study, consuming either 5 or 10 g of mushrooms daily. Each subject had blood drawn before and after 4 weeks of daily L. edodes consumption.

[1338] Bao Y et al. Shiitake-derived β-D-glucan mixture modulates gut microbiota in hypercholesterolemic adults: an 8-week RCT 2024;15(5):2568-2580. Food Funct. 2024.

8-week RCT on a shiitake-derived β-D-glucan mixture modulating gut microbiota in hypercholesterolemic adults (Food Funct).

[1339] Oba K et al. Individual patient-based meta-analysis of lentinan for unresectable/recurrent gastric cancer2009;29(7):2739-2745. Anticancer Res. Link

BACKGROUND: In the present study, the effect of immunochemotherapy with lentinan compared with that of chemotherapy alone was evaluated in patients with advanced gastric cancer through individual patient data (IPD) meta-analysis. MATERIALS AND METHODS: Based on a computerized and manual search, all eligible centrally randomized controlled trials (RCT) which compared chemotherapy regimens with or without lentinan administration for advanced gastric cancer patients were included. RESULTS: In total, 650 IPD from 5 trials were available. Lentinan significantly prolonged the overall survival (stratified log-rank p=0.011). The overall hazard ratio (HR) was 0.80 (95\% confidence interval=0.68-0.95) and there was no heterogeneity between trials. Additionally, lentinan was possibly more effective in patients with lymph-node metastasis than in non-node metastasis patients (P for interaction=0.077).

[1340] Wasser SP. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides2002;60(3):258-274. Appl Microbiol Biotechnol. Link

The number of mushrooms on Earth is estimated at 140,000, yet maybe only 10\% (approximately 14,000 named species) are known. Mushrooms comprise a vast and yet largely untapped source of powerful new pharmaceutical products. In particular, and most importantly for modern medicine, they represent an unlimited source of polysaccharides with antitumor and immunostimulating properties. Many, if not all, Basidiomycetes mushrooms contain biologically active polysaccharides in fruit bodies, cultured mycelium, culture broth. Data on mushroom polysaccharides have been collected from 651 species and 7 infraspecific taxa from 182 genera of higher Hetero- and Homobasidiomycetes. These polysaccharides are of different chemical composition, with most belonging to the group of beta-glucans; these have beta-(1-->3) linkages in the main chain of the glucan and additional beta-(1-->6) branch points that are needed for their antitumor action.

[1341] Bisen PS et al. Lentinula edodes: a macrofungus with pharmacological activities2010;17(22):2419-2430. Curr Med Chem. Link

Lentinus edodes is the first medicinal macrofungus to enter the realm of modern biotechnology. It is the second most popular edible mushroom in the global market which is attributed not only to its nutritional value but also to possible potential for therapeutic applications. Lentinus edodes is used medicinally for diseases involving depressed immune function (including AIDS), cancer, environmental allergies, fungal infection, frequent flu and colds, bronchial inflammation, heart disease, hyperlipidemia (including high blood cholesterol), hypertension, infectious disease, diabetes, hepatitis and regulating urinary inconsistencies. It is the source of several well-studied preparations with proven pharmacological properties, especially the polysaccharide lentinan, eritadenine, shiitake mushroom mycelium, and culture media extracts (LEM, LAP and KS-2). Antibiotic, anti-carcinogenic and antiviral compounds have been isolated intracellularly (fruiting body and mycelia) and extracellularly (culture media). Some of these substances were lentinan, lectins and eritadenine.

[1342] Cardwell G et al. A review of mushrooms as a potential source of dietary vitamin D2018;10(10):1498. Nutrients. Link

When commonly consumed mushroom species are exposed to a source of ultraviolet (UV) radiation, such as sunlight or a UV lamp, they can generate nutritionally relevant amounts of vitamin D. The most common form of vitamin D in mushrooms is D₂, with lesser amounts of vitamins D₃ and D₄, while vitamin D₃ is the most common form in animal foods. Although the levels of vitamin D₂ in UV-exposed mushrooms may decrease with storage and cooking, if they are consumed before the 'best-before' date, vitamin D₂ level is likely to remain above 10 μg/100 g fresh weight, which is higher than the level in most vitamin D-containing foods and similar to the daily requirement of vitamin D recommended internationally. Worldwide mushroom consumption has increased markedly in the past four decades, and mushrooms have the potential to be the only non-animal, unfortified food source of vitamin D that can provide a substantial amount of vitamin D₂ in a single serve. This review examines the current information on the role of UV radiation in enhancing the concentration of vitamin D₂ in mushrooms, the effects of storage and cooking on vitamin D₂ content, and the bioavailability of vitamin D₂ from mushrooms.

[1343] Boggess SS et al. UV-treated mushrooms increase 25-hydroxyvitamin D status in humans 2017;105(1):106-113. Am J Clin Nutr. 2017.

Study on UV-treated mushrooms increasing 25-hydroxyvitamin D status in humans (Am J Clin Nutr).

[1344] Hossen MA et al. Shiitake-related dermatitis: clinical features and pathophysiology 2018;28(6):779-784. Eur J Dermatol. 2018.

Article on the clinical features and pathophysiology of shiitake-related dermatitis (Eur J Dermatol).

[1346] EFSA NDA Panel. Safety of UV-treated mushroom powder as a novel food 2020;18(7):6190. EFSA Journal. 2020.

EFSA NDA Panel opinion on the safety of UV-treated mushroom powder as a novel food (EFSA Journal).

[1347] Hess J et al. Effects of Agaricus bisporus consumption on gut microbiota in healthy adults: a randomized crossover trial2018;118(8):1503-1512. J Acad Nutr Diet. Link

Eating Agaricus bisporus mushrooms may impact gut health, because they contain known prebiotics. This study assessed mushroom consumption compared to meat on gastrointestinal tolerance, short chain fatty acid (SCFA) production, laxation, and fecal microbiota. A randomized open-label crossover study was conducted in healthy adults (n = 32) consuming protein-matched amounts of mushrooms or meat twice daily for ten days. Breath hydrogen measures were taken on day one, and gastrointestinal tolerance was evaluated throughout treatments. Fecal sample collection was completed days 6⁻10, and samples were assessed for bacterial composition, SCFA concentrations, weight, pH, and consistency. There were no differences in breath hydrogen, stool frequency, consistency, fecal pH, or SCFA concentrations between the two diets.

[1348] Urbain P et al. Bioavailability of vitamin D2 from UV-B-irradiated button mushrooms (Agaricus bisporus) in healthy adults deficient in serum 25-hydroxyvitamin D: a randomized controlled trial2011;65(8):965-971. Eur J Clin Nutr. Link

BACKGROUND/OBJECTIVES: Mushrooms contain very little or any vitamin D(2) but are abundant in ergosterol, which can be converted into vitamin D(2) by ultraviolet (UV) irradiation. Our objective was to investigate the bioavailability of vitamin D(2) from vitamin D(2)-enhanced mushrooms by UV-B in humans, and comparing it with a vitamin D(2) supplement. SUBJECTS/METHODS: Fresh mushrooms were irradiated with an UV-B dose of 1.5 J/cm(2), increasing vitamin D(2) content from <1 to 491 μg/100 g and made to an experimental soup. In this 5-week, single-blinded, randomized, placebo-controlled trial, 26 young subjects with serum 25-hydroxyvitamin D (25OHD) ≤ 50 nmol/l were randomly assigned into three groups ((a) mushroom, (b) supplement and (c) placebo). They received during winter (a) 28,000 IU (700 μg) vitamin D(2) via the experimental soup, or (b) 28,000 IU vitamin D(2) via a supplement or (c) placebo, respectively. RESULTS: After 2 weeks, serum 25OHD was significantly higher in the mushroom than in the placebo group (P=0.001).

[1349] Beelman RB et al. Health consequences of improving the content of ergothioneine in the food supply2020;594(20):3262-3268. FEBS Lett. Link

Ergothioneine (ERGO) is a potent antioxidant and anti-inflammatory amino acid that is highly bioavailable to humans from the diet. ERGO is now regarded by some as a 'longevity vitamin' that has the potential to mitigate some chronic diseases of ageing and thereby increase life expectancy when present in adequate amounts. However, only limited knowledge exists regarding ERGO content in the human diet. Since ERGO is produced primarily by fungi, mushrooms are known to be the leading dietary source, but ERGO is found in relatively low amounts throughout the food chain as a result of soil-borne fungi or bacteria passing it on to plants through their roots. Some conventional agricultural practices that negatively impact soil fungi, such as excessive soil disturbance (ploughing), can significantly reduce ERGO content of food crops when compared to regenerative practices such as eliminating tillage of the soil (no-till). This has led us to the concept that ERGO may be a definitive connection between soil health and human health.

[1350] Calvo MS et al. Vitamin D2 from UV-exposed mushrooms — efficacy review 2024;16(11):1623. Nutrients. 2024.

Efficacy review of vitamin D2 from UV-exposed mushrooms (Nutrients).

[1351] Yu S et al. Agaricus bisporus and antiobesity effects on gut microbiota and inflammation: animal and human studies 2022;11(18):2890. Foods. 2022.

Review of animal and human studies on Agaricus bisporus and antiobesity effects on gut microbiota and inflammation (Foods).

[1354] Smith JE et al. Medicinal mushrooms: their therapeutic properties and current medical usage with special emphasis on cancer treatments report 2002. Cancer Research UK. 2002.

Report on medicinal mushrooms, their therapeutic properties and current medical usage with special emphasis on cancer treatments (Cancer Research UK).

[1356] Kawagishi H et al. Hericenones C, D, and E, stimulators of nerve growth factor (NGF)-synthesis, from the mushroom Hericium erinaceum. Tetrahedron Letters 1991;32(35):4561–4564. . 1991. Link

Experimental chemistry paper describing hericenones C, D and E isolated from the mushroom Hericium erinaceum as stimulators of nerve growth factor (NGF) synthesis.

[1357] Mori K et al. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytother Res 2009;23(3):367–372. . 2009. Link

A double-blind, parallel-group, placebo-controlled trial was performed on 50- to 80-year-old Japanese men and women diagnosed with mild cognitive impairment in order to examine the efficacy of oral administration of Yamabushitake (Hericium erinaceus), an edible mushroom, for improving cognitive impairment, using a cognitive function scale based on the Revised Hasegawa Dementia Scale (HDS-R). After 2 weeks of preliminary examination, 30 subjects were randomized into two 15-person groups, one of which was given Yamabushitake and the other given a placebo. The subjects of the Yamabushitake group took four 250 mg tablets containing 96\% of Yamabushitake dry powder three times a day for 16 weeks. After termination of the intake, the subjects were observed for the next 4 weeks. At weeks 8, 12 and 16 of the trial, the Yamabushitake group showed significantly increased scores on the cognitive function scale compared with the placebo group. The Yamabushitake group's scores increased with the duration of intake, but at week 4 after the termination of the 16 weeks intake, the scores decreased significantly.

[1358] Saitsu Y et al. Improvement of cognitive functions by oral intake of Hericium erinaceus. Biomedical Research 2019;40(4):125–131. . 2019. Link

Randomized, double-blind, placebo-controlled parallel-group trial: participants took a supplement containing Hericium erinaceus fruiting body or placebo for 12 weeks. Cognitive function was assessed by MMSE, Benton visual retention test, and standard verbal paired-associate learning test; by MMSE, oral intake of H. erinaceus significantly improved cognitive function and prevented its deterioration.

[1359] Li IC et al. Prevention of early Alzheimer's disease by erinacine A-enriched Hericium erinaceus mycelia pilot double-blind placebo-controlled study. Frontiers in Aging Neuroscience 2020;12:155. . 2020. Link

OBJECTIVE: To investigate the efficacy and safety of three H. erinaceus mycelia (EAHE) capsules (350 mg/capsule; containing 5 mg/g erinacine A active ingredient) per day for the treatment of patients with mild Alzheimer's Disease (AD). METHODS: This study comprised a 3-week no-drug screening period, followed by a 49-week double-blind treatment period with 2-parallel groups in which eligible patients were randomized to either three 5 mg/g EAHE mycelia capsules per day or identical appearing placebo capsules. Cognitive assessments, ophthalmic examinations, biomarker collection, and neuroimaging were followed throughout the study period. RESULTS: After 49 weeks of EAHE intervention, a significant decrease in Cognitive Abilities Screening Instrument score was noted in the placebo group, a significant improvement in Mini-Mental State Examination score was observed in the EAHE group and a significant Instrumental Activities of Daily Living score difference were found between the two groups. In addition, EAHE group achieved a significantly better contrast sensitivity when compared to the placebo group. Moreover, only the placebo group observed significantly lowered biomarkers such as calcium, albumin, apolipoprotein E4, hemoglobin, and brain-derived neurotrophic factor and significantly elevated alpha1-antichymotrypsin and amyloid-beta peptide 1-40 over the study period.

[1360] Nagano M et al. Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Biomedical Research 2010;31(4):231–237. . 2010. Link

Hericium erinaceus, a well known edible mushroom, has numerous biological activities. Especially hericenones and erinacines isolated from its fruiting body stimulate nerve growth factor (NGF) synthesis, which expects H. erinaceus to have some effects on brain functions and autonomic nervous system. Herein, we investigated the clinical effects of H. erinaceus on menopause, depression, sleep quality and indefinite complaints, using the Kupperman Menopausal Index (KMI), the Center for Epidemiologic Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Indefinite Complaints Index (ICI). Thirty females were randomly assigned to either the H. erinaceus (HE) group or the placebo group and took HE cookies or placebo cookies for 4 weeks. Each of the CES-D and the ICI score after the HE intake was significantly lower than that before. In two terms of the ICI, "insentive" and "palpitatio", each of the mean score of the HE group was significantly lower than the placebo group. "Concentration", "irritating" and "anxious" tended to be lower than the placebo group.

[1361] Friedman M. Chemistry, nutrition, and health-promoting properties of Hericium erinaceus mushroom fruiting bodies and mycelia. J Agric Food Chem 2015;63(32):7108–7123. . 2015. Link

The culinary and medicinal mushroom Hericium erinaceus is widely consumed in Asian countries, but apparently not in the United States, for its nutritional and health benefits. To stimulate broader interest in the reported beneficial properties, this overview surveys and consolidates the widely scattered literature on the chemistry (isolation and structural characterization) of polysaccharides and secondary metabolites such as erinacines, hericerins, hericenones, resorcinols, steroids, mono- and diterpenes, and volatile aroma compounds, nutritional composition, food and industrial uses, and exceptional nutritional and health-promoting aspects of H. erinaceus. The reported health-promoting properties of the mushroom fruit bodies, mycelia, and bioactive pure compounds include antibiotic, anticarcinogenic, antidiabetic, antifatigue, antihypertensive, antihyperlipodemic, antisenescence, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties and improvement of anxiety, cognitive function, and depression. The described anti-inflammatory, antioxidative, and immunostimulating properties in cells, animals, and humans seem to be responsible for the multiple health-promoting properties. A wide range of research advances and techniques are described and evaluated. The collated information and suggestion for further research might facilitate and guide further studies to optimize the use of the whole mushrooms and about 70 characterized actual and potential bioactive secondary metabolites to help prevent or treat human chronic, cognitive, and neurological diseases.

[1362] Wang M et al. Effects of polysaccharides from Hericium erinaceus on gut microbiota. Carbohydr Polym 2019;217:30–38. . 2019.

Study on the effects of polysaccharides from Hericium erinaceus on the gut microbiota.

[1363] Spelman K et al. Neurological activity of Lion's mane (Hericium erinaceus). J Restor Med 2017;6(1):19–26. . 2017.

Review article on the neurological activity of Lion's mane (Hericium erinaceus).

[1364] Nanba H. Antitumor activity of orally administered "D-fraction" from maitake mushroom (Grifola frondosa). J Naturopath Med 1993;4(1):10–15. . 1993.

Paper on the antitumor activity of orally administered "D-fraction" from the maitake mushroom (Grifola frondosa).

[1365] Kodama N et al. Effect of Maitake (Grifola frondosa) D-Fraction on the activation of NK cells in cancer patients. J Med Food 2003;6(4):371–377. . 2003. Link

Maitake D-Fraction, extracted from maitake mushroom, has been reported to exert its antitumor effect in tumor-bearing mice by enhancing the immune system through activation of macrophages, T cells, and natural killer (NK) cells. In a previous study, the combination of immunotherapy with the maitake D-Fraction and chemotherapy suggested that the D-Fraction may have the potential to decrease the size of lung, liver, and breast tumors in cancer patients. In the present study, we administered maitake D-Fraction to cancer patients without anticancer drugs, and at the same time NK cell activity was monitored to investigate whether the activity is closely related with disease progression. The numbers of CD4(+) and CD8(+) cells in the peripheral blood were measured in 10 patients, and NK cell activity was assessed using K-562 cells as target cells. Serum soluble interleukin-2 receptor (sIL-2R) levels in three patients and the expression of tumor markers in four patients were determined by enzyme-linked immunosorbent assay. The slight changes observed in the CD4(+) and CD8(+) cell numbers were independent of disease severity or stage as well as serum sIL-2R levels.

[1366] Kodama N et al. Can maitake MD-fraction aid cancer patients? Altern Med Rev 2002;7(3):236–239. . 2002.

Article examining whether maitake MD-fraction can aid cancer patients.

[1367] Konno S et al. A possible hypoglycaemic effect of maitake mushroom on type 2 diabetic patients. Diabet Med 2001;18(12):1010. . 2001. Link

A brief clinical observation (case-report type): two Type 2 diabetic patients received daily maitake mushroom caplets (500 mg) alongside glibenclamide, and their blood glucose dropped sharply into the normal range, allowing reduction or withdrawal of glibenclamide. The authors hypothesize that maitake acts by increasing insulin receptor activity or sensitivity.

[1368] Mayell M. Maitake extracts and their therapeutic potential — a review. Altern Med Rev 2001;6(1):48–60. . 2001.

Review article on maitake extracts and their therapeutic potential.

[1369] Vetvicka V, Vetvickova J. Immune-enhancing effects of Maitake (Grifola frondosa) and Shiitake (Lentinula edodes) extracts. Ann Transl Med 2014;2(2):14. . 2014.

Study on the immune-enhancing effects of Maitake (Grifola frondosa) and Shiitake (Lentinula edodes) extracts.

[1370] Deng G et al. A phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients. J Cancer Res Clin Oncol 2009;135(9):1215–1221. . 2009. Link

BACKGROUND: Cancer patients commonly use dietary supplements to "boost immune function". A polysaccharide extract from Grifola frondosa (Maitake extract) showed immunomodulatory effects in preclinical studies and therefore the potential for clinical use. Whether oral administration in human produces measurable immunologic effects, however, is unknown. METHODS: In a phase I/II dose escalation trial, 34 postmenopausal breast cancer patients, free of disease after initial treatment, were enrolled sequentially in five cohorts. Maitake liquid extract was taken orally at 0.1, 0.5, 1.5, 3, or 5 mg/kg twice daily for 3 weeks. Peripheral blood was collected at days -7, 0 (prior to the first dosing), 7, 14, and 21 for ex vivo analyses.

[1371] Chen S et al. Anti-diabetic effects of Grifola frondosa polysaccharides and underlying mechanisms. Carbohydr Polym 2020;229:115524. . 2020.

Paper on the anti-diabetic effects of Grifola frondosa polysaccharides and their underlying mechanisms.

[1372] Wachtel-Galor S et al. Ganoderma lucidum (Lingzhi or Reishi): A Medicinal Mushroom. In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd ed. Boca Raton: CRC Press; 2011. . 2011. Link

Book chapter presenting Ganoderma lucidum (Lingzhi or Reishi) as a medicinal mushroom.

[1373] Cui XY et al. Extract of Ganoderma lucidum prolongs sleep time in rats. J Ethnopharmacol 2012;139(3):796–800. . 2012. Link

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (Ling Zhi) is a basidiomycete white-rot macrofungus that has been used as a tranquilizing agent (i.e., An-Shen effect) for the treatment of restlessness, insomnia, and palpitation in China for hundreds of years. AIM OF THE STUDY: The present study aimed to investigate whether Ganoderma lucidum extract (GLE) influences the sleep of freely moving rats and the potential mechanism. MATERIALS AND METHODS: Ganoderma lucidum extract was extracted from fruiting bodies of Ganoderma lucidum. Rats were treated with GLE orally for 3 days, and on the third day, electroencephalographic and electromyographic recordings were made for 6h from 9:00 p.m. to 3:00 a.m. in freely moving rats. Sleep parameters were analyzed using SleepSign software. Tumor necrosis factor-α (TNF-α) levels were measured using the enzyme-linked immunosorbent assay.

[1374] Sun LX et al. Polysaccharides from Ganoderma lucidum and immunomodulation. Int J Biol Macromol 2014;65:537–544. . 2014.

Paper on polysaccharides from Ganoderma lucidum and immunomodulation.

[1375] Tang W et al. A randomized, double-blind, placebo-controlled trial of Ganoderma lucidum polysaccharide extract in neurasthenia. J Med Food 2005;8(1):53–58. . 2005. Link

Ganoderma lucidum has been widely used to treat various diseases, including cancer, diabetes, and neurasthenia in many Asian countries. This randomized, double-blind, placebo-controlled parallel study aimed to investigate the efficacy and safety of a polysaccharide extract of G. lucidum (Ganopoly) in Chinese patients with neurasthenia. One hundred thirty-two patients with neurasthenia according to the diagnosis criteria of the 10th International Classification of Diseases were included in this study. Written consents were obtained from the patients, and the study was conducted in accordance with Good Clinical Practice guidelines. Patients were randomized to receive Ganopoly or placebo orally at 1,800 mg three times a day for 8 weeks. Efficacy assessments comprised the Clinical Global Impression (CGI) improvement of severity scale and the Visual Analogues Scales for the sense of fatigue and well-being.

[1376] Jin X et al. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev 2016;4:CD007731. . 2016. Link

BACKGROUND: Ganoderma lucidum is a natural medicine that is widely used and recommended by Asian physicians and naturopaths for its supporting effects on immune system. Laboratory research and a handful of preclinical trials have suggested that G. lucidum carries promising anticancer and immunomodulatory properties. The popularity of taking G. lucidum as an alternative medicine has been increasing in cancer patients. However, there is no systematic review that has been conducted to evaluate the actual benefits of G. lucidum in cancer treatment. OBJECTIVES: To evaluate the clinical effects of G. lucidum on long-term survival, tumour response, host immune functions and quality of life in cancer patients, as well as adverse events associated with its use. SEARCH METHODS: We searched an extensive set of databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, NIH, AMED, CBM, CNKI, CMCC and VIP Information/Chinese Scientific Journals Database was searched for randomised controlled trials (RCTs) in October 2011.

[1377] Tao J, Feng KY. Experimental and clinical studies on inhibitory effect of Ganoderma lucidum on platelet aggregation. J Tongji Med Univ 1990;10(4):240–243. . 1990. Link

Experimental and clinical study of the inhibitory effect of Ganoderma lucidum on platelet aggregation in 15 healthy volunteers and 33 patients with atherosclerotic disease. In vitro, the water-soluble extract dose-dependently inhibited the first and second phases of platelet aggregation; after patients took 1 g three times daily for 2 weeks, ADP-induced aggregation was significantly reduced.

[1378] Wanmuang H et al. Fatal fulminant hepatitis associated with Ganoderma lucidum (Lingzhi) mushroom powder. J Med Assoc Thai 2007;90(1):179–181. . 2007.

Case report of fatal fulminant hepatitis associated with Ganoderma lucidum (Lingzhi) mushroom powder.

[1379] Chang CJ et al. Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat Commun 2015;6:7489. . 2015. Link

Obesity is associated with low-grade chronic inflammation and intestinal dysbiosis. Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative anti-diabetic effects. Here, we show that a water extract of Ganoderma lucidum mycelium (WEGL) reduces body weight, inflammation and insulin resistance in mice fed a high-fat diet (HFD). Our data indicate that WEGL not only reverses HFD-induced gut dysbiosis-as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels-but also maintains intestinal barrier integrity and reduces metabolic endotoxemia. The anti-obesity and microbiota-modulating effects are transmissible via horizontal faeces transfer from WEGL-treated mice to HFD-fed mice. We further show that high molecular weight polysaccharides (>300 kDa) isolated from the WEGL extract produce similar anti-obesity and microbiota-modulating effects.

[1380] Bishop KS et al. From 2000 years of Ganoderma lucidum to recent developments in nutraceuticals. Phytochemistry 2015;114:56–65. . 2000. Link

Medicinal mushrooms have been used for centuries as nutraceuticals to improve health and to treat numerous chronic and infectious diseases. One such mushroom is Ganoderma lucidum, commonly known as Lingzhi, a species revered as a medicinal mushroom for treating assorted diseases and prolonging life. The fungus is found in diverse locations, and this may have contributed to confusion regarding the correct taxonomic classification of the genus Ganoderma. G. lucidum was first used to name a specimen found in England and thereafter was naively applied to a different Ganoderma species found in Asia, commonly known as Chinese Lingzhi. Despite the taxonomic confusion, which has largely been uncorrected, the popularity of Lingzhi has escalated across the globe. The current taxonomic situation is now discussed accurately in this Special Issue on Ganoderma.

[1381] Gunde-Cimerman N et al. Lovastatin in oyster mushrooms (Pleurotus ostreatus). FEMS Microbiol Lett 1993;113(3):333–337. . 1993. Link

In the fruiting bodies of the fungus Pleurotus ostreatus, also called the oyster mushroom, we found a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase-lovastatin. The appearance of the inhibitor during the development of fruiting bodies was followed and lovastatin determined in the vegetative mycelium, in the primordia, as well as in different parts of sporocarps of different sizes. Less lovastatin was found in stripes as compared to pili or in mature stages in the lamellae and basidiospores.

[1382] Bobek P, Galanc J. Effect of pleuran (β-glucan from Pleurotus ostreatus) on the antioxidant status of the organism in rats. Physiol Res 1998;47(3):247–250. . 1998.

Rat experiment on pleuran (β-glucan from Pleurotus ostreatus) and its effect on the antioxidant status of the organism.

[1383] Khatun K et al. Oyster mushroom reduced blood glucose and cholesterol in diabetic subjects. Mymensingh Med J 2007;16(1):94–99. . 2007. Link

Clinical study (BIRDEM hospital, 89 subjects) with a 24-day repeated-feeding design (7 days mushroom / 7 days off / 7 days mushroom). Oyster mushroom significantly reduced blood glucose, blood pressure, triglycerides, and cholesterol in diabetic subjects without deleterious effects on liver or kidney, with partial reversal during the washout period.

[1384] Schneider I et al. Lipid lowering effects of oyster mushroom (Pleurotus ostreatus) in humans. J Funct Foods 2011;3(1):17–24. . 2011. Link

Human intervention study: 20 young adults (9 male, 11 female; 20-34 years) were randomized to consume daily either a soup containing 30 g dried oyster mushrooms or a tomato soup as placebo for 21 days, to investigate the cholesterol-lowering properties of oyster mushroom (Pleurotus ostreatus) in humans.

[1385] Jesenak M et al. Pleuran (β-glucan from Pleurotus ostreatus) in recurrent respiratory tract infections in children. Phytother Res 2013;27(11):1638–1645. . 2013. Link

Recurrent respiratory tract infections (RRTIs) present a very important problem in paediatric praxis. As true immunodeficiencies are rare, one of the most important factors assumed to contribute to increased respiratory morbidity is atopy. Several preparations of natural origin have been used for the prevention of RRTIs, and some of the most effective immunomodulators are biologically active polysaccharides - e.g. ß-glucans. In our randomised, double-blind, placebo-controlled study, we investigated the prevalence of atopy in a group of children with RRTIs and the potential anti-allergic effect of pleuran (ß-glucan isolated from Pleurotus ostreatus) on basic laboratory markers of allergic inflammation. We confirmed that atopy may be an important factor contributing to the increased respiratory morbidity in children with RRTIs. The active treatment with pleuran resulted in a significant reduction of peripheral blood eosinophilia and stabilised the levels of total IgE in serum.

[1386] Patel Y et al. An overview of potential oyster mushroom Pleurotus species. Biomed Pharmacother 2012;3(1):1–12. . 2012.

Overview article on potential oyster mushroom Pleurotus species.

[1387] Cohen R et al. Biotechnological applications and potential of wood-degrading mushrooms of the genus Pleurotus. Appl Microbiol Biotechnol 2002;58(5):582–594. . 2002. Link

The genus Pleurotus comprises a group of edible ligninolytic mushrooms with medicinal properties and important biotechnological and environmental applications. The cultivation of Pleurotus spp is an economically important food industry worldwide which has expanded in the past few years. P. ostreatus is the third most important cultivated mushroom for food purposes. Nutritionally, it has unique flavor and aromatic properties; and it is considered to be rich in protein, fiber, carbohydrates, vitamins and minerals. Pleurotus spp are promising as medicinal mushrooms, exhibiting hematological, antiviral, antitumor, antibiotic, antibacterial, hypocholesterolic and immunomodulation activities. The bioactive molecules isolated from the different fungi are polysaccharides.

[1388] Manzi P et al. Beta-glucans in edible mushrooms. Food Chem 2001;73(3):321–325. . 2001.

Paper on beta-glucans in edible mushrooms.

[1389] Chen S et al. Effect of Cs-4 (Cordyceps sinensis) on exercise performance in healthy older subjects: a double-blind, placebo-controlled trial. J Altern Complement Med 2010;16(5):585–590. . 2010. Link

OBJECTIVE: The objective of this study was to examine the effect of Cs-4 (Cordyceps sinensis) on exercise performance in healthy elderly subjects. DESIGN: Twenty (20) healthy elderly (age 50-75 years) subjects were enrolled in this double-blind, placebo-controlled, prospective trial. The subjects were taking either Cs-4 333 mg or placebo capsules 3 times a day for 12 weeks. MEASUREMENT: Subjects received baseline screening including physical examination and laboratory tests. Maximal incremental exercise testing was performed on a stationary cycle ergometer using breath-by-breath analysis at baseline and at the completion of the study. RESULTS: After receiving Cs-4 for 12 weeks, the metabolic threshold (above which lactate accumulates) increased by 10.5\% from 0.83 +/- 0.06 to 0.93 +/- 0.08 L/min (p < 0.02) and the ventilatory threshold (above which unbuffered H(+) stimulates ventilation) increased by 8.5\% from 1.25 +/- 0.11 to 1.36 +/- 0.15 L/min.

[1390] Hirsch KR et al. Cordyceps militaris improves tolerance to high-intensity exercise after acute and chronic supplementation. J Diet Suppl 2017;14(1):42–53. . 2017. Link

To determine the effects of a mushroom blend containing Cordyceps militaris on high-intensity exercise after 1 and 3 weeks of supplementation. Twenty-eight individuals (Mean ± standard deviation [SD]; Age = 22.7 ± 4.1 yrs; Height = 175.4 ± 8.7 cm; Weight = 71.6 ± 12.0 kg) participated in this randomized, repeated measures, double-blind, placebo-controlled design. Maximal oxygen consumption (VO2max), time to exhaustion (TTE), and ventilatory threshold (VT) were measured during a maximal graded exercise test on a cycle ergometer. Relative peak power output (RPP), average power output (AvgP), and percent drop (\%drop) were recorded during a 3 minute maximal cycle test with resistance at 4.5\% body weight. Subjects consumed 4 g·d-1 mushroom blend (MR) or maltodextrin (PL) for 1 week. Ten volunteers supplemented for an additional 2 weeks.

[1391] Tuli HS et al. Pharmacological and therapeutic potential of Cordyceps with special reference to cordycepin. 3 Biotech 2014;4(1):1–12. . 2014. Link

An entomopathogenic fungus, Cordyceps sp. has been known to have numerous pharmacological and therapeutic implications, especially, in terms of human health making it a suitable candidate for ethno-pharmacological use. Main constituent of the extract derived from this fungus comprises a novel bio-metabolite called as Cordycepin (3'deoxyadenosine) which has a very potent anti-cancer, anti-oxidant and anti-inflammatory activities. The current review discusses about the broad spectrum potential of Cordycepin including biological and pharmacological actions in immunological, hepatic, renal, cardiovascular systems as well as an anti-cancer agent. The article also reviews the current efforts to delineate the mechanism of action of Cordycepin in various bio-molecular processes. The study will certainly draw the attention of scientific community to improve the bioactivity and production of Cordycepin for its commercial use in pharmacological and medical fields.

[1392] Liu Y et al. The chemical constituents and pharmacological actions of Cordyceps sinensis. Evid Based Complement Alternat Med 2015;2015:575063. . 2015.

Review article on the chemical constituents and pharmacological actions of Cordyceps sinensis.

[1393] Hsu CC et al. Regulatory effects of Cordyceps sinensis on testosterone production in mouse Leydig cells. Life Sci 2003;73(16):2127–2136. . 2003. Link

In vivo and in vitro study on mouse Leydig cells: among Cordyceps sinensis (CS) and its extracted fractions, F2 (water-soluble protein) and F3 (poorly soluble polysaccharide/protein) significantly stimulated testosterone production in a dose- and time-dependent manner (maximal at 3 mg/mL, 3 h), whereas F1 (water-soluble polysaccharide) had no effect; in vivo, CS, F2, and F3 increased plasma testosterone.

[1394] Wang J et al. Pharmacological mechanisms underlying the neuroprotective effects of Cordyceps. J Ethnopharmacol 2017;199:178–195. . 2017.

Paper on the pharmacological mechanisms underlying the neuroprotective effects of Cordyceps.

[1395] Yi X et al. Randomized double-blind placebo-controlled clinical trial and assessment of fermentation product of Cordyceps sinensis (Cs-4) in enhancing aerobic capacity and respiratory function. Chin J Integr Med 2004;10(3):187–192. . 2004. Link

Randomized, double-blind, placebo-controlled clinical trial in 37 healthy elderly Chinese subjects: Cs-4 (a fermentation product of Cordyceps sinensis, 3 g/day) or placebo for 6 weeks, tested by cycle-ergometer exercise. In the Cs-4 group, maximum oxygen uptake (VO2max) and anaerobic threshold (VO2θ) increased significantly, whereas they were unchanged in the placebo group.

[1396] Liu C et al. Effects of Cordyceps militaris on exercise performance: a meta-analysis. J Strength Cond Res 2021;35(suppl). . 2021.

Meta-analysis on the effects of Cordyceps militaris on exercise performance.

[1397] Sakamoto J et al. Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials. Cancer Immunol Immunother 2006;55(4):404–411. . 2006. Link

The benefits of immunochemotherapy employing the biological response modifier polysaccharide K (PSK) for patients with curatively resected colorectal cancer was reassessed by means of a meta-analysis of data with center randomization from 1,094 patients enrolled in three clinical trials. In all three trials, patients were followed up for at least 5 years after surgery and enrollment of the last patient and outcomes for standard chemotherapy were compared with those for chemotherapy plus PSK. The endpoints were overall survival and disease-free survival; and intent-to-treat analysis was performed without patient exclusion. Data were analyzed using the weighted average of the individual log hazard ratios. The overall survival risk ratio for all eligible patients was 0.71 (95\% confidence interval (CI) : 0.55-0.90; P=0.006), and the disease-free survival risk ratio was 0.72 (95\% CI: 0.58-0.90; P=0.003). The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK can improve both survival and disease-free survival of patients with curatively resected colorectal cancer.

[1398] Oba K et al. Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curative resections of gastric cancer. Cancer Immunol Immunother 2007;56(6):905–911. . 2007. Link

Non-specific immunopotentiators, such as polysaccharide K (PSK), also known as OK-432, induce anti-tumor effects via immunological responses. The efficacy of combination immunochemotherapy using these immunopotentiators has been examined by multiple previous studies. The survival benefits of immunochemotherapy for patients with curative resections of gastric cancers are not widely accepted. To clarify this issue, we performed a meta-analysis to evaluate the effect of immunochemotherapy on survival in patients with curative resections of gastric cancer. For this study, we compared the results of chemotherapy and immunotherapy using the biological response modifier PSK as an immunopotentiator. The meta-analysis included 8,009 patients from eight randomized controlled trials after central randomization.

[1399] Eliza WL et al. Efficacy of Yun Zhi (Coriolus versicolor) on survival in cancer patients: systematic review and meta-analysis. Recent Pat Inflamm Allergy Drug Discov 2012;6(1):78–87. . 2012. Link

Systematic review and meta-analysis of randomized, placebo-controlled, double-blind trials evaluating the effect of Yun Zhi (Coriolus versicolor) on survival in cancer patients. The analysis found that Yun Zhi was associated with an absolute reduction in 5-year mortality (about 9%), corresponding to one additional survivor for roughly every 11 patients treated. The benefit was most pronounced in breast, colorectal and gastric cancer patients treated with chemotherapy.

[1400] Standish LJ et al. Trametes versicolor mushroom immune therapy in breast cancer: a phase I trial. ISRN Oncol 2008;2008:251632. . 2008.

Phase I clinical trial of Trametes versicolor mushroom immune therapy in breast cancer.

[1401] Iino Y et al. Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer. Anticancer Res 1995;15(6B):2907–2911. . 1995.

Paper comparing immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer.

[1402] Pallav K et al. Effects of polysaccharopeptide from Trametes versicolor on gut microbiota in humans. ISRN Microbiology 2014;2014:548604. . 2014. Link

BACKGROUND: Interactions between the microbial flora of the intestine and the human host play a critical role inmaintaining intestinal health and in the pathophysiology of a wide variety of disorders such as antibiotic associated diarrhea, Clostridium difficile infection, and inflammatory bowel disease. Prebiotics can confer health benefits by beneficial effects on the intestinal microbiome, whereas antibiotics can disrupt the microbiome leading to diarrhea andother side effects. AIM: To compare the effects of the prebiotic, polysaccharopeptide from Trametes versicolor, to those of the antibiotic,amoxicillin, on the human gut microbiome METHODS: Twenty-four healthy volunteers were randomized to receive PSP, amoxicillin, or no treatment (control).Stool specimens were analyzed using bTEFAP microbial ecology methods on seven occasions over 8 weeks from each participant in the active treatment groups and on three occasions for the controls. RESULTS: Twenty-two of 24 participants completed the protocol. PSP led to clear and consistent microbiome changes consistent with its activity as a prebiotic. Despite the diversity of the human microbiome we noted strong microbiome clustering among subjects.

[1403] Wong CK et al. Immunomodulatory activities of Yun Zhi and Danshen in post-treatment breast cancer patients. Am J Chin Med 2005;33(3):381–395. . 2005. Link

Clinical trial in 82 breast cancer patients who took Yunzhi (100% polysaccharopeptide, PSP) plus Danshen capsules daily for 6 months after treatment; immune function was assessed every two months by flow cytometry and ELISA. After supplementation the absolute counts of T-helper (CD4+) cells, the CD4+/CD8+ ratio, and the percentage and counts of B-lymphocytes rose significantly, while plasma soluble IL-2 receptor (sIL-2R) concentration fell. The authors concluded that regular Yunzhi-Danshen intake may beneficially support immune function in post-treatment breast cancer patients.

[1404] Kidd PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev 2000;5(1):4–27. . 2000.

Review article on the use of mushroom glucans and proteoglycans in cancer treatment.

[1405] Reis F.S. et al. (2012):Food Research International, 49(2):816–825. Chemical composition and nutritional value of the most widely appreciated cultivated mushrooms. 2012. Link

Herein, it was reported and compared the chemical composition and nutritional value of the most consumed species as fresh cultivated mushrooms: Agaricus bisporus (white and brown mushrooms), Pleurotus ostreatus (oyster mushroom), Pleurotus eryngii (King oyster mushroom), Lentinula edodes (Shiitake) and Flammulina velutipes (Golden needle mushroom). Shiitake revealed the highest levels of macronutrients, unless proteins, as also the highest sugars, tocopherols and PUFA levels, and the lowest SFA content. White and brown mushrooms showed similar macronutrients composition, as also similar values of total sugars, MUFA, PUFA and total tocopherols. Oyster and king oyster mushrooms gave the highest MUFA contents with similar contents in PUFA, MUFA and SFA in both samples. They also revealed similar moisture, ash, carbohydrates and energy values. This study contributes to the elaboration of nutritional databases of the most consumed fungi species worldwide, allowing comparison between them.

[1406] Halliwell B. et al. (2018):FEBS Letters, 592(20):3357–3366. Ergothioneine — a diet-derived antioxidant with therapeutic potential. 2018. Link

Ergothioneine is a thiol/thione molecule synthesised only by some fungi and bacteria. Nonetheless, it is avidly taken up from the diet by humans and other animals through a transporter, OCTN1, and accumulates to high levels in certain tissues. Ergothioneine is not rapidly metabolised, or excreted in urine and is present in many, if not all, human tissues and body fluids. Ergothioneine has powerful antioxidant and cytoprotective properties in vitro and there is evidence that the body may concentrate it at sites of tissue injury by raising OCTN1 levels. Decreased blood and/or plasma levels of ergothioneine have been observed in some diseases, suggesting that a deficiency could be relevant to the disease onset or progression. This brief Review explores the possible roles of ergothioneine in human health and disease.

[1407] . Beelman R.B., Kalaras M.D. (2017): The FASEB Journal. Ergothioneine and vitamin D2 in mushrooms — implications for cognitive decline. 2017.

Paper on ergothioneine and vitamin D2 in mushrooms and their implications for cognitive decline.

[1408] Heleno S.A. et al. (2010): Food Chemistry, 119(4):1443–1450. Tocopherols composition of Portuguese wild mushrooms with antioxidant capacity. 2010.

Study on the tocopherols composition of Portuguese wild mushrooms with antioxidant capacity.

[1409] Kalač P. (2009):Food Chemistry, 113(1):9–16. Chemical composition and nutritional value of European species of wild growing mushrooms: A review. 2009. Link

Review of the chemical composition and nutritional value of European wild-growing mushroom species. The author summarizes the main macro- and micronutrients, noting that mushrooms are a notable mineral source, with K, P, Mg and Ca predominating along with copper, iron and zinc. The review also covers protein, carbohydrate and fibre content, serving as a reference for assessing the nutritional value of mushrooms.

[1410] . Falandysz J., Borovička J. (2013): Applied Microbiology and Biotechnology, 97(2):477–501. Macro and trace mineral constituents and radionuclides in mushrooms — health benefits and risks. 2013.

Review article on macro and trace mineral constituents and radionuclides in mushrooms, addressing health benefits and risks.

[1411] . Magyar Mikológiai Társaság (2018): . Boletus edulis és rokonai a magyar gombászatban. 2018. Link

Publication by the Hungarian Mycological Society on Boletus edulis and its relatives in Hungarian mycology.

[1412] Heleno SA et al. Food Chem. 2015;173:501–513. Bioactivity of phenolic acids: metabolites versus parent compounds: a review. 2015.

Review article on the bioactivity of phenolic acids, comparing metabolites versus parent compounds.

[1413] Vamanu E, Pelinescu D LWT Food Sci Technol. 2017;85:262–268. Effects of mushroom consumption on the microbiota of different target groups — impact of polyphenolic composition and mitigation on the microbiome fingerprint. 2017.

Study on the effects of mushroom consumption on the microbiota of different target groups, addressing polyphenolic composition and the microbiome fingerprint.

[1414] EFSA NDA Panel. Scientific Opinion on the substantiation of a health claim related to oat beta-glucan and lowering blood cholesterol2010;8(12):1885. EFSA Journal. Link

Scientific Opinion of the EFSA NDA Panel on the substantiation of a health claim related to oat beta-glucan and lowering blood cholesterol.

[1415] . U.S. FDA(21 CFR 101.81). 1997. Food labeling: health claims; oats and coronary heart disease. 1997. Link

U.S. FDA food labeling regulation (21 CFR 101.81) on the health claim regarding oats and coronary heart disease.

[1416] Whitehead A et al. Cholesterol-lowering effects of oat β-glucan: a meta-analysis of randomized controlled trials2014;100(6):1413–1421. Am J Clin Nutr. Link

BACKGROUND: Health claims regarding the cholesterol-lowering effect of soluble fiber from oat products, approved by food standards agencies worldwide, are based on a diet containing ≥3 g/d of oat β-glucan (OBG). Given the number of recently published randomized controlled trials (RCTs), it is important to update the findings of previous meta-analyses. OBJECTIVE: The objective was to quantify the effect of ≥3 g OBG/d on serum cholesterol concentrations in humans and investigate potential effect modifiers. DESIGN: A meta-analysis was performed on 28 RCTs comparing ≥3 g OBG/d with an appropriate control. Systematic searches were undertaken in PubMed, AGRICOLA, and Scopus between 1 January 1966 and 6 June 2013, plus in-house study reports at CreaNutrition AG. Studies were assessed with regard to inclusion/exclusion criteria, and data were extracted from included studies by reviewers working independently in pairs, reconciling differences by consensus.

[1417] Wolever TMS et al. Physicochemical properties of oat β-glucan influence its ability to reduce serum LDL cholesterol2010;92(4):723–732. Am J Clin Nutr. Link

BACKGROUND: Consumption of 3 g oat β-glucan/d is considered sufficient to lower serum LDL cholesterol, but some studies have shown no effect. LDL cholesterol lowering by oat β-glucan may depend on viscosity, which is controlled by the molecular weight (MW) and amount of oat β-glucan solubilized in the intestine (C). OBJECTIVES: Our 2 primary objectives were to determine whether consumption of 3 g high-MW oat β-glucan/d would reduce LDL cholesterol and whether LDL cholesterol lowering was related to the log(MW × C) of oat β-glucan. DESIGN: In a double-blind, parallel-design, multicenter clinical trial, subjects with LDL cholesterol ≥3.0 and ≤5.0 mmol/L (n = 786 screened, n = 400 ineligible, n = 19 refused, n = 367 enrolled, and n = 345 completed) were randomly assigned to receive cereal containing wheat fiber (n = 87) or 3 g high-MW (2,210,000 g/mol, n = 86), 4 g medium-MW (850,000 g/mol, n = 67), 3 g medium-MW (530,000 g/mol, n = 64), or 4 g low-MW (210,000 g/mol, n = 63) oat β-glucan/d (divided doses, twice daily) for 4 wk. RESULTS: LDL cholesterol was significantly less with 3 g high-MW, 4 g medium-MW, and 3 g medium-MW oat β-glucan cereals than with the wheat-fiber cereal by 0.21 (5.5\%; 95\% CI: -0.11, -0.30; P = 0.002), 0.26 (6.5\%; 95\% CI: -0.14, -0.37; P = 0.0007), and 0.19 (4.7\%; 95\% CI: -0.08, -0.30; P = 0.01) mmol/L, respectively. However, the effect of 4 g low-MW oat β-glucan/d (0.10 mmol/L) was not significant (2.3\%; 95\% CI: 0.02, -0.20).

[1418] Meydani M. Potential health benefits of avenanthramides of oats2009;67(12):731–735. Nutr Rev. Link

Oats are known to be a healthy food for the heart due mainly to their high beta-glucan content. In addition, they contain more than 20 unique polyphenols, avenanthramides, which have shown strong antioxidant activity in vitro and in vivo. The polyphenols of oats have also recently been shown to exhibit anti-inflammatory, antiproliferative, and anti-itching activity, which may provide additional protection against coronary heart disease, colon cancer, and skin irritation.

[1419] Connolly ML et al. Hypocholesterolemic and prebiotic effects of beta-glucan-enriched oat-based products in humans 2016. J Funct Foods. 2016.

Human study on the hypocholesterolemic and prebiotic effects of beta-glucan-enriched oat-based products.

[1420] Pulido OM et al. Safety of pure oats in coeliac disease: a systematic review 2008. Aliment Pharmacol Ther. 2008.

Systematic review on the safety of pure oats in coeliac disease.

[1422] EFSA NDA Panel. Scientific Opinion on the substantiation of a health claim related to barley beta-glucan and lowering blood cholesterol2011;9(12):2470. EFSA Journal. Link

Scientific Opinion of the EFSA NDA Panel on the substantiation of a health claim related to barley beta-glucan and lowering blood cholesterol.

[1423] AbuMweis SS et al. β-glucan from barley and its lipid-lowering capacity: a meta-analysis of randomized controlled trials2010;64(12):1472–1480. Eur J Clin Nutr. Link

BACKGROUND/OBJECTIVES: To more precisely quantify the effect of barley β-glucan on blood lipid concentrations in humans and to examine the factors that could affect its efficacy. SUBJECTS/METHODS: Eleven eligible randomized clinical trials published from 1989 to 2008 were identified from nine databases. Weighted mean effect sizes were calculated for net differences in lipid profile using a random effect model (RevMan 4.2). RESULTS: Overall, barley and β-glucan isolated from barley lowered total and low-density lipoprotein (LDL) cholesterol concentrations by 0.30 mmol/l (95\% confidence interval (CI): -0.39 to -0.21, P<0.00001) and 0.27 mmol/l (95\% CI: -0.34 to -0.20, P<0.00001), respectively, compared with control. The pattern of cholesterol-lowering action of barley in this analysis could not be viewed as a dose-dependent response. There were no significant subgroup differences by type of intervention and food matrix.

[1424] Wang Y et al. High-molecular-weight β-glucan decreases serum cholesterol differentially based on the CYP7A1 rs3808607 polymorphism in mildly hypercholesterolemic adults 2016;146(4):720–727. J Nutr. 2016. Link

Dietary intervention study in mildly hypercholesterolemic adults comparing the cholesterol-lowering effect of high-molecular-weight (HMW) versus low-molecular-weight (LMW) barley β-glucan in relation to the CYP7A1 rs3808607 polymorphism. Consuming 3 g/d HMW β-glucan significantly lowered total cholesterol (about -0.12 mmol/L) versus control, whereas LMW β-glucan (3 or 5 g/d) did not change serum cholesterol. The effect showed a gene-diet interaction: carriers of the rs3808607 G allele responded with greater total-cholesterol reduction than TT carriers.

[1425] EFSA NDA Panel. Health claim related to barley β-glucans and reduction of post-prandial glycaemic responses2011;9(6):2207. EFSA Journal. Link

EFSA NDA Panel scientific opinion on the substantiation of health claims for barley (and oat) β-glucans under Article 13(1) of Regulation (EC) No 1924/2006, including reduction of post-prandial glycaemic responses. The Panel concluded that a cause-and-effect relationship was established between β-glucan consumption and reduction of post-prandial glycaemic response. To obtain the claimed effect, the opinion states that at least 4 g of oat or barley β-glucan should be consumed for each 30 g of available carbohydrate.

[1426] De Angelis M et al. Effect of whole-grain barley on the human fecal microbiota and metabolome2015;81(22):7945–7956. Appl Environ Microbiol. Link

In this study, we compared the fecal microbiota and metabolomes of 26 healthy subjects before (HS) and after (HSB) 2 months of diet intervention based on the administration of durum wheat flour and whole-grain barley pasta containing the minimum recommended daily intake (3 g) of barley β-glucans. Metabolically active bacteria were analyzed through pyrosequencing of the 16S rRNA gene and community-level catabolic profiles. Pyrosequencing data showed that levels of Clostridiaceae (Clostridium orbiscindens and Clostridium sp.), Roseburia hominis, and Ruminococcus sp. increased, while levels of other Firmicutes and Fusobacteria decreased, from the HSB samples to the HS fecal samples. Community-level catabolic profiles were lower in HSB samples. Compared to the results for HS samples, cultivable lactobacilli increased in HSB fecal samples, while the numbers of Enterobacteriaceae, total coliforms, and Bacteroides, Porphyromonas, Prevotella, Pseudomonas, Alcaligenes, and Aeromonas bacteria decreased. Metabolome analyses were performed using an amino acid analyzer and gas chromatography-mass spectrometry solid-phase microextraction.

[1427] Aoe S et al. Effect of cooked white rice with high β-glucan barley on appetite and energy intake in healthy Japanese subjects: a randomized controlled trial 2017;72(2):198–203. Plant Foods Hum Nutr. 2017. Link

Randomized crossover dietary study in 21 healthy Japanese women examining the effect of cooked white rice with high-β-glucan barley on appetite and energy intake versus plain white rice. The β-glucan-barley breakfast significantly reduced hunger and prospective food consumption and increased fullness before lunch; energy intake at lunch and cumulative (lunch + dinner) energy intake were also lower. The authors suggest combining white rice with high-β-glucan barley may help prevent obesity and related metabolic disease. (Note: the source was published in 2014.)

[1428] Bays HE et al. Reduced viscosity barley β-glucan vs placebo: a randomized controlled trial 2011. Nutr J. 2011.

Randomized controlled trial comparing reduced viscosity barley β-glucan versus placebo.

[1429] . Newman RK, Newman CW Wiley-Blackwell, 2008. Barley for Food and Health. 2008.

Book on barley for food and health.

[1430] Giacco R et al. Effects of rye and whole wheat versus refined cereal foods on metabolic risk factors: a randomised controlled two-centre intervention study 2014;24(8):837–844. Nutr Metab Cardiovasc Dis. 2014. Link

Randomized controlled two-centre (Finland and Italy) dietary intervention in adults with metabolic syndrome comparing rye and whole-wheat cereal foods with refined cereal foods on metabolic risk factors over 12 weeks. The wholegrain diet did not improve peripheral insulin sensitivity relative to refined cereals. Some analyses indicated the wholegrain diet favourably affected post-prandial insulin and triglyceride responses, with no significant effects on fasting parameters.

[1431] Damen B et al. Prebiotic effects and intestinal fermentation of cereal arabinoxylans and arabinoxylan oligosaccharides in rats depend strongly on their structural properties 2011;59(2):553–562. J Agric Food Chem. 2011. Link

Rat study examining the prebiotic effects and intestinal fermentation of cereal arabinoxylans (AX) and arabinoxylan oligosaccharides (AXOS) as a function of their structural properties. Water-unextractable AX-rich (WU-AX), water-extractable AX (WE-AX), AXOS and combinations were tested at a 5% AX level. WU-AX was only partially fermented in the ceco-colon and increased butyrate levels and butyrate-producing Roseburia; prebiotic effects depended strongly on the structural features of AX and on their joint presence.

[1432] Vuholm S et al. Whole-grain rye, but not whole-grain wheat, lowers body weight and fat mass compared with refined wheat: a 6-week randomized study2018;148(1):76–83. J Nutr. Link

BACKGROUND: Observational studies suggest inverse associations between wholegrain intake and body weight gain. Only few controlled intervention studies have supported this association and few compare effects of different grain varieties. OBJECTIVE: To investigate how wholegrain wheat (WGW) and rye compared with refined wheat (RW) affect body weight and composition and appetite sensation. DESIGN: Seventy overweight/obese adults participated in this 6-week randomized parallel study, in which they replaced their habitual cereal foods with RW, WGW or wholegrain rye (WGR). Further, a 4 h postprandial test meal challenge was completed with meals corresponding to diet allocation in the beginning and after the intervention. Body weight and composition, fasted blood samples, compliance and 4-day dietary intake were obtained before and after the intervention period.

[1433] Eriksen AK et al. Effects of whole-grain wheat, rye, and lignans on the digestive system: a randomized crossover study 2020. Br J Nutr. 2020.

Randomized crossover study on the effects of whole-grain wheat, rye, and lignans on the digestive system.

[1434] EFSA NDA Panel. Scientific Opinion on dietary reference values for carbohydrates and dietary fibre2010;8(3):1462. EFSA Journal. Link

Scientific Opinion of the EFSA NDA Panel on dietary reference values for carbohydrates and dietary fibre.

[1435] Landberg R et al. Alkylresorcinols as biomarkers of whole-grain wheat and rye intake2008;87(4):832–838. Am J Clin Nutr. Link

BACKGROUND: Alkylresorcinols (ARs), phenolic lipids exclusively present in the outer parts of wheat and rye grains, have been proposed as specific dietary biomarkers of whole-grain wheat and rye intake. OBJECTIVE: The objective was to validate plasma ARs as a biomarker of whole-grain wheat and rye intakes by studying the correlation between their plasma concentration and intake calculated from food records. DESIGN: In a randomized crossover study, 22 women and 8 men were given a defined amount of either whole-grain or refined-cereal-grain products to be included in their habitual diets for two 6-wk periods. Blood samples were collected and food intakes were recorded before and after each intervention period. RESULTS: Plasma AR concentrations were significantly higher after the whole-grain diet period than after the refined-grain period (P < 0.0001) and were well correlated with average daily AR intake estimated by self-reported weighed food records (Spearman's r = 0.58, P < 0.001). CONCLUSION: Plasma AR concentrations are correlated with intake assessed by food records, which suggests that ARs are selective nutritional biomarkers for the intake of whole-grain wheat and rye.

[1436] Lappi J et al. Sourdough fermentation of wholemeal wheat bread increases solubility of arabinoxylan and protein and decreases postprandial glucose and insulin responses 2010;51(1):152–158. J Cereal Sci. 2010. Link

Study analyzing the effect of sourdough fermentation on the solubility of arabinoxylan and protein in wholemeal wheat bread and on post-prandial glucose and insulin responses, in 11 insulin-resistant subjects. Sourdough fermentation increased water-extractable arabinoxylan and soluble protein content and reduced the molecular weight of hydrolysed proteins. Among the three tested wheat breads, the sourdough bread produced the most favourable post-prandial glucose and insulin responses; proposed mechanisms include low pH, increased arabinoxylan solubilisation and proteolysis.

[1437] Laatikainen R et al. Pilot study: comparison of sourdough wheat bread and yeast-fermented wheat bread in individuals with wheat sensitivity and IBS2017;9(11):1215. Nutrients. Link

Many patients suspect wheat as being a major trigger of their irritable bowel syndrome (IBS) symptoms. Our aim was to evaluate whether sourdough wheat bread baked without baking improvers and using a long dough fermentation time (>12 h), would result in lower quantities of alpha-amylase/trypsin inhibitors (ATIs) and Fermentable, Oligo-, Di-, Mono-saccharides and Polyols (FODMAPs), and would be better tolerated than yeast-fermented wheat bread for subjects with IBS who have a poor subjective tolerance to wheat. The study was conducted as a randomised double-blind controlled 7-day study (n = 26). Tetrameric ATI structures were unravelled in both breads vs. baking flour, but the overall reduction in ATIs to their monomeric form was higher in the sourdough bread group. Sourdough bread was also lower in FODMAPs. However, no significant differences in gastrointestinal symptoms and markers of low-grade inflammation were found between the study breads.

[1438] Pomp ER et al. Sourdough rye bread and IBS tolerance 2020. Nutrients. 2020.

Paper on sourdough rye bread and IBS tolerance.

[1439] Costabile A et al. Whole-grain wheat breakfast cereal has a prebiotic effect on the human gut microbiota: a double-blind, placebo-controlled, crossover study2008;99(1):110–120. Br J Nutr. Link

Epidemiological studies have shown an inverse association between dietary intake of whole grains and the risk of chronic disease. This may be related to the ability to mediate a prebiotic modulation of gut microbiota. However, no studies have been conducted on the microbiota modulatory capability of whole-grain (WG) cereals. In the present study, the impact of WG wheat on the human intestinal microbiota compared to wheat bran (WB) was determined. A double-blind, randomised, crossover study was carried out in thirty-one volunteers who were randomised into two groups and consumed daily 48 g breakfast cereals, either WG or WB, in two 3-week study periods, separated by a 2-week washout period. Numbers of faecal bifidobacteria and lactobacilli (the target genera for prebiotic intake), were significantly higher upon WG ingestion compared with WB.

[1440] Vitaglione P et al. Whole-grain wheat consumption reduces inflammation in a randomized controlled trial 2015;101(2):251–261. Am J Clin Nutr. 2015.

Randomized controlled trial reporting that whole-grain wheat consumption reduces inflammation.

[1441] Walton GE et al. A randomised, double-blind, placebo-controlled cross-over study to determine the gastrointestinal effects of consumption of arabinoxylan-oligosaccharides enriched bread 2012;11:36. Nutr J. 2012. Link

Randomized, double-blind, placebo-controlled crossover study in 40 healthy adults examining the gastrointestinal effects of bread enriched with in situ-produced arabinoxylan oligosaccharides (AXOS, about 2.2 g) versus non-treated control bread. Consumption of AXOS-enriched bread increased faecal butyrate and showed a trend toward reduced iso-valerate and fatty acids associated with protein fermentation. No adverse gastrointestinal symptoms were reported; the AXOS bread was well tolerated and produced a potentially beneficial shift in fermentation end products.

[1442] Biesiekierski JR et al. No effects of gluten in patients with self-reported NCGS after dietary reduction of FODMAPs2013;145(2):320–328. Gastroenterology. Link

BACKGROUND \& AIMS: Patients with non-celiac gluten sensitivity (NCGS) do not have celiac disease but their symptoms improve when they are placed on gluten-free diets. We investigated the specific effects of gluten after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates (fermentable, oligo-, di-, monosaccharides, and polyols [FODMAPs]) in subjects believed to have NCGS. METHODS: We performed a double-blind cross-over trial of 37 subjects (aged 24-61 y, 6 men) with NCGS and irritable bowel syndrome (based on Rome III criteria), but not celiac disease. Participants were randomly assigned to groups given a 2-week diet of reduced FODMAPs, and were then placed on high-gluten (16 g gluten/d), low-gluten (2 g gluten/d and 14 g whey protein/d), or control (16 g whey protein/d) diets for 1 week, followed by a washout period of at least 2 weeks. We assessed serum and fecal markers of intestinal inflammation/injury and immune activation, and indices of fatigue. Twenty-two participants then crossed over to groups given gluten (16 g/d), whey (16 g/d), or control (no additional protein) diets for 3 days.

[1443] Skodje GI et al. Fructan, rather than gluten, induces symptoms in patients with self-reported non-coeliac gluten sensitivity 2018;154(3):529–539. Gastroenterology. 2018. Link

Double-blind crossover challenge study in 59 individuals with self-reported non-coeliac gluten sensitivity on a self-instituted gluten-free diet (coeliac disease excluded), evaluating the effects of gluten and fructan separately. Fructan, rather than gluten, significantly triggered gastrointestinal symptoms in these patients. The findings suggest that symptoms attributed to non-coeliac gluten sensitivity may, at least in part, be driven by FODMAP-type fructans.

[1444] EFSA NDA Panel. Scientific Opinion on the substantiation of health claims related to wheat bran fibre and increase in faecal bulk2010;8(10):1817. EFSA Journal. Link

Scientific Opinion of the EFSA NDA Panel on the substantiation of health claims related to wheat bran fibre and increase in faecal bulk.

[1445] Aune D et al. Whole grain consumption and risk of cardiovascular disease, cancer, and all-cause mortality: a meta-analysis2016;353:i2716. BMJ. Link

OBJECTIVE: To quantify the dose-response relation between consumption of whole grain and specific types of grains and the risk of cardiovascular disease, total cancer, and all cause and cause specific mortality. DATA SOURCES: PubMed and Embase searched up to 3 April 2016. STUDY SELECTION: Prospective studies reporting adjusted relative risk estimates for the association between intake of whole grains or specific types of grains and cardiovascular disease, total cancer, all cause or cause specific mortality. DATA SYNTHESIS: Summary relative risks and 95\% confidence intervals calculated with a random effects model. RESULTS: 45 studies (64 publications) were included. The summary relative risks per 90 g/day increase in whole grain intake (90 g is equivalent to three servings-for example, two slices of bread and one bowl of cereal or one and a half pieces of pita bread made from whole grains) was 0.81 (95\% confidence interval 0.75 to 0.87; I(2)=9\%, n=7 studies) for coronary heart disease, 0.88 (0.75 to 1.03; I(2)=56\%, n=6) for stroke, and 0.78 (0.73 to 0.85; I(2)=40\%, n=10) for cardiovascular disease, with similar results when studies were stratified by whether the outcome was incidence or mortality.

[1447] EFSA Panel CONTAM. Dietary exposure to inorganic arsenic in the European population2014;12(3):3597. EFSA Journal. Link

EFSA CONTAM Panel scientific report on dietary exposure to inorganic arsenic in the European population. The estimate drew on the EFSA Comprehensive European Food Consumption Database, covering 28 surveys from 17 countries and a total of 103,773 food samples (including drinking water), though a large proportion of total-arsenic data were below the limit of detection/quantification. The report identified grain-based products, rice, and milk and dairy products as the main contributors to exposure.

[1448] Sengupta MK et al. Arsenic burden of cooked rice: traditional and modern methods 2006;40(2):512–518. Environ Sci Technol. 2006.

Study on the arsenic burden of cooked rice using traditional and modern methods.

[1449] Cicero AF, Gaddi A. Rice bran oil and γ-oryzanol in the treatment of hyperlipoproteinaemias and other conditions 2001;15(4):277–289. Phytother Res. 2001. Link

Review of the role of rice bran oil and γ-oryzanol in the treatment of hyperlipoproteinaemias and other conditions. The authors report that rice bran oil and its main components (unsaturated fatty acids, triterpene alcohols, phytosterols, tocotrienols, alpha-tocopherol) can improve the plasma lipid profile, lowering total cholesterol and triglycerides and raising HDL cholesterol. Other potential effects include inhibition of gastric acid secretion, antioxidant activity and inhibition of platelet aggregation.

[1450] Sonia S et al. Cooling of cooked white rice reduces the postprandial blood glucose response in healthy subjects2015;24(4):620–625. Asia Pac J Clin Nutr. Link

[1451] Sheflin AM et al. Stabilized rice bran improves stool frequency: a randomized controlled trial 2017. Br J Nutr. 2017.

Randomized controlled trial reporting that stabilized rice bran improves stool frequency.

[1452] Park HY et al. Brown rice intake and gut microbiota modulation 2020. Nutrients. 2020.

Study on brown rice intake and gut microbiota modulation.

[1454] . WHO 2018. Arsenic in drinking water and rice-based foods — public health guidance. 2018. Link

WHO fact sheet on arsenic in drinking water and rice-based foods, providing public health guidance.

[1456] Awika JM, Rooney LW. Sorghum phytochemicals and their potential impact on human health2004;65(9):1199–1221. Phytochemistry. Link

Sorghum is a rich source of various phytochemicals including tannins, phenolic acids, anthocyanins, phytosterols and policosanols. These phytochemicals have potential to significantly impact human health. Sorghum fractions possess high antioxidant activity in vitro relative to other cereals or fruits. These fractions may offer similar health benefits commonly associated with fruits. Available epidemiological evidence suggests that sorghum consumption reduces the risk of certain types of cancer in humans compared to other cereals. The high concentration of phytochemicals in sorghum may be partly responsible.

[1457] Stefoska-Needham A et al. A diet enriched with red sorghum flaked biscuits modulates the gut microbiota in overweight men 2017. Mol Nutr Food Res. 2017.

Study on how a diet enriched with red sorghum flaked biscuits modulates the gut microbiota in overweight men.

[1458] Ricci L et al. Symbiotic food approach in CKD patients: reduction of uremic toxins by sorghum-based diet 2022. Nutrients. 2022.

Study on a symbiotic food approach in CKD patients, reducing uremic toxins with a sorghum-based diet.

[1459] Yang L et al. 3-Deoxyanthocyanidins from black sorghum: bioactivity and stability 2014. J Agric Food Chem. 2014.

Paper on 3-deoxyanthocyanidins from black sorghum, addressing their bioactivity and stability.

[1460] Khan I et al. Sorghum grain: from genotype, nutrition, and phenolic profile to its health benefits — a comprehensive review 2015. Food Chem. 2015.

Comprehensive review article on sorghum grain, from genotype, nutrition, and phenolic profile to its health benefits.

[1461] Ciacci C et al. Celiac disease: in vitro and in vivo safety of sorghum 2007. Clin Nutr. 2007.

Paper examining the in vitro and in vivo safety of sorghum in celiac disease.

[1462] Wedad HA et al. Influence of fermentation on tannin content and digestibility of sorghum-based foods 2008. Food Sci Nutr. 2008.

Study on the influence of fermentation on the tannin content and digestibility of sorghum-based foods.

[1463] EAT-Lancet Commission. Food in the Anthropocene: planetary health diet2019. Lancet. Link

EAT-Lancet Commission report ('Food in the Anthropocene'), bringing together experts from 16 countries to define global scientific targets for healthy diets and sustainable food production. The report describes a universal healthy reference diet (the 'planetary health diet'), emphasizing increased intake of vegetables, fruits, whole grains, legumes and nuts and reduced intake of red meat, sugar and refined grains. The targets define a 'safe operating space' for food systems consistent with sustainability and climate goals.

[1465] Van den Abbeele P et al. Arabinoxylans from corn bran modulate gut microbiota composition and SCFA profile in vivo 2018. Br J Nutr. 2018.

In vivo study on how arabinoxylans from corn bran modulate gut microbiota composition and the SCFA profile.

[1466] Maki KC et al. Resistant starch from high-amylose maize increases insulin sensitivity in overweight and obese men2012;142(4):717–723. J Nutr. Link

This study evaluated the effects of 2 levels of intake of high-amylose maize type 2 resistant starch (HAM-RS2) on insulin sensitivity (S(I)) in participants with waist circumference ≥89 (women) or ≥102 cm (men). Participants received 0 (control starch), 15, or 30 g/d (double-blind) of HAM-RS2 in random order for 4-wk periods separated by 3-wk washouts. Minimal model S(I) was assessed at the end of each period using the insulin-modified i.v. glucose tolerance test. The efficacy evaluable sample included 11 men and 22 women (mean ± SEM) age 49.5 ± 1.6 y, with a BMI of 30.6 ± 0.5 kg/m2 and waist circumference 105.3 ± 1.3 cm. A treatment main effect (P = 0.018) and a treatment × sex interaction (P = 0.033) were present. In men, least squares geometric mean analysis for S(I) did not differ after intake of 15 g/d HAM-RS2 (6.90 × 10⁻⁵ pmol⁻¹ · L⁻¹ × min⁻¹) and 30 g/d HAM-RS2 (7.13 × 10⁻⁵ pmol⁻¹ · L⁻¹ × min⁻¹), but both were higher than after the control treatment (4.66 × 10⁻⁵ pmol⁻¹ · L⁻¹ × min⁻¹) (P < 0.05).

[1467] Whisner CM et al. Soluble corn fiber increases calcium absorption associated with shifts in the gut microbiome: a randomized dose-response trial2016;146(7):1298–1306. J Nutr. Link

BACKGROUND: Soluble corn fiber (SCF; 12 g fiber/d) is shown to increase calcium absorption efficiency, associated with shifts in the gut microbiota in adolescent males and females who participated in a controlled feeding study. OBJECTIVE: We evaluated the dose response of 0, 10, and 20 g fiber/d delivered by PROMITOR SCF 85 (85\% fiber) on calcium absorption, biochemical bone properties, and the fecal microbiome in free-living adolescents. METHODS: Healthy adolescent females (n = 28; aged 11-14 y) randomly assigned into a 3-phase, double-blind, crossover study consumed SCF for 4 wk at each dose (0, 10, and 20 g fiber/d from SCF) alongside their habitual diet and were followed by 3-d clinical visits and 3-wk washout periods. Stable isotope ((44)Ca and (43)Ca) enrichment in pooled urine was measured by inductively coupled plasma mass spectrometry. Fecal microbial community composition was assessed by high-throughput sequencing (Illumina) of polymerase chain reaction-amplified 16S rRNA genes. Mixed model ANOVA and Friedman analysis were used to determine effects of SCF on calcium absorption and to compare mean microbial proportions, respectively.

[1468] Bouis HE, Saltzman A. Improving nutrition through biofortification: a review of evidence from HarvestPlus, 2003–2016 2017;12:49–58. Glob Food Sec. 2003. Link

Review summarizing the evidence on the nutritional impact of biofortification based on HarvestPlus program work from 2003 through 2016. The authors conclude that biofortification—increasing micronutrients (e.g., iron, zinc, provitamin A) via plant breeding—is a feasible and cost-effective way to address micronutrient deficiency in populations with limited access to diverse diets. Since 2003, millions of farm households in developing countries have been growing and consuming biofortified crops.

[1469] Bressani R, Scrimshaw NS. The history of corn and pellagra 1986. Annu Rev Nutr. 1986.

Review article on the history of corn and pellagra.

[1470] Mora-Avilés A et al. Nixtamalization processes for maize: nutritional, sensorial and structural impact 2017. Food Chem. 2017.

Food-chemistry paper on nixtamalization (alkaline-cooking) processes for maize, reviewing their nutritional, sensorial and structural impact.

[1471] Chiremba C et al. Determinants of polyphenols in maize 2012. Cereal Chem. 2012.

Cereal-chemistry article on the determinants of polyphenols in maize.

[1472] Bingham SA et al. Whole grain intake and cancer risk: epidemiological evidence 2003. Br J Cancer. 2003.

Epidemiological review of the evidence linking whole grain intake and cancer risk.

[1474] Zevallos VF et al. Variable activation of immune response by quinoa (Willd.) prolamins in celiac disease. Am J Clin Nutr 2012;96(2):337–344. Chenopodium quinoa. 2012. Link

BACKGROUND: Celiac disease is an enteropathy triggered by dietary gluten found in wheat, barley, and rye. The current treatment is a strict gluten-free diet. Quinoa is a highly nutritive plant from the Andes, with low concentrations of prolamins, that has been recommended as part of a gluten-free diet; however, few experimental data support this recommendation. OBJECTIVE: We aimed to determine the amount of celiac-toxic prolamin epitopes in quinoa cultivars from different regions of the Andes and the ability of these epitopes to activate immune responses in patients with celiac disease. DESIGN: The concentration of celiac-toxic epitopes was measured by using murine monoclonal antibodies against gliadin and high-molecular-weight glutenin subunits. Immune response was assessed by proliferation assays of celiac small intestinal T cells/interferon-γ (IFN-γ) and production of IFN-γ/IL-15 after organ culture of celiac duodenal biopsy samples.

[1475] Vega-Gálvez A et al. Nutrition facts and functional potential of quinoa (Chenopodium quinoa Willd.)2010;90(15):2541–2547. J Sci Food Agric. 2010. Link

Quinoa, Chenopodium quinoa Willd., is an Amaranthacean, stress-tolerant plant cultivated along the Andes for the last 7000 years, challenging highly different environmental conditions ranging from Bolivia, up to 4.500 m of altitude, to sea level, in Chile. Its grains have higher nutritive value than traditional cereals and it is a promising worldwide cultivar for human consumption and nutrition. The quinoa has been called a pseudo-cereal for botanical reasons but also because of its unusual composition and exceptional balance between oil, protein and fat. The quinoa is an excellent example of 'functional food' that aims at lowering the risk of various diseases. Functional properties are given also by minerals, vitamins, fatty acids and antioxidants that can make a strong contribution to human nutrition, particularly to protect cell membranes, with proven good results in brain neuronal functions. Its minerals work as cofactors in antioxidant enzymes, adding higher value to its rich proteins.

[1476] Repo-Carrasco-Valencia R et al. Quinoa and other Andean grains: polyphenol and flavonoid composition 2010. J Cereal Sci. 2010.

Cereal-science study of the polyphenol and flavonoid composition of quinoa and other Andean grains.

[1477] Navarro-Perez D et al. Quinoa-enriched bread modulates gut microbiota in healthy men: a randomized crossover trial 2022. Nutrients. 2022.

Randomized crossover trial examining the effect of quinoa-enriched bread on the gut microbiota in healthy men.

[1478] García-Parra M et al. Quinoa-based biscuit pilot RCT 2024. Food Funct. 2024.

Pilot randomized controlled trial of a quinoa-based biscuit.

[1479] . FAO 2013. Quinoa: an ancient crop to contribute to world food security. 2013. Link

FAO document presenting quinoa as an ancient crop contributing to world food security.

[1480] Filho AMM et al. Quinoa proteins: composition, structure and properties 2017. Crit Rev Food Sci Nutr. 2017.

Review article on the composition, structure and properties of quinoa proteins.

[1481] . NASA Technical Paper 34221993. Quinoa: candidate crop for NASA's Controlled Ecological Life Support System. Link

NASA technical paper discussing quinoa as a candidate crop for the Controlled Ecological Life Support System.

[1483] Li SQ, Zhang QH. Advances in the development of functional foods from buckwheat2001;41(6):451–464. Crit Rev Food Sci Nutr. Link

Buckwheat originated in North or East Asia and is widely adapted in North America. It has been grown since at least 1000 BC in China. It has very strong adaptability to adverse environments with a very short growing span. Many varieties are growing around the world, but mainly in the north hemisphere. Currently the most common buckwheat spice is Fagopyrum esculentum Moench (common buckwheat or sweet buckwheat), while Fagopyrum tartaricum is also available in some mountainous regions. Many nutraceutical compounds exist in buckwheat seeds and other tissues.

[1484] Pacheco LS et al. D-chiro-inositol from buckwheat improves insulin resistance in metabolic syndrome: a pilot RCT 2010. Nutrition. 2010.

Pilot RCT on D-chiro-inositol from buckwheat for improving insulin resistance in metabolic syndrome.

[1485] Christa K, Soral-Smietana M. Buckwheat grains and buckwheat products — nutritional and prophylactic value 2008;26(3):153–162. Czech J Food Sci. 2008. Link

Review of the nutritional and prophylactic value of buckwheat grains and buckwheat products. The authors note that buckwheat is rich in starch, high-biological-value proteins, antioxidants, dietary fibre and trace elements, and contains bioactive components such as flavonoids (e.g., rutin), fagopyrins and thiamin-binding proteins. In animal models buckwheat flour alleviated diabetes, obesity, hypertension and hypercholesterolemia, making it a valuable ingredient in health-promoting diets.

[1486] Hou Z et al. Rutin from buckwheat is metabolized by human gut microbiota into bioactive phenolic acids 2017. Food Funct. 2017.

Study showing that rutin from buckwheat is metabolized by the human gut microbiota into bioactive phenolic acids.

[1487] Skrabanja V et al. Resistant starch in buckwheat: cook-cool cycle effects 2007. J Agric Food Chem. 2007.

Food-chemistry paper on resistant starch in buckwheat and the effects of the cook-cool cycle.

[1488] Wieslander G, Norbäck D. Buckwheat allergy 2001;56(8):703–704. Allergy. 2001.

Allergology note on buckwheat allergy.

[1489] Stojilkovski K et al. Fagopyrin content in buckwheat grain, sprouts, and herba 2013. Pharmacogn Mag. 2013.

Study of fagopyrin content in buckwheat grain, sprouts, and herba.

[1490] Holasova M et al. Polyphenolic compounds in buckwheat 2002. Czech J Food Sci. 2002.

Food-science article on polyphenolic compounds in buckwheat.

[1492] Saleh AS et al. Millet grains: nutritional quality, processing, and potential health benefits2013;12(3):281–295. Compr Rev Food Sci Food Saf. Link

Review of the nutritional quality, processing, and potential health benefits of millet grains. The authors summarize millet's nutrient composition, noting that as a drought-resistant crop it is a major source of carbohydrates and proteins in the semiarid tropics of Africa and Asia. The review discusses processing technologies for improving the edible and nutritional characteristics of millet, along with the challenges and prospects for wider use of millet as food.

[1493] Anitha S et al. A systematic review and meta-analysis of the potential of millets and sorghum for managing and preventing diabetes mellitus 2021. Front Nutr. 2021.

Systematic review and meta-analysis of the potential of millets and sorghum for managing and preventing diabetes mellitus.

[1494] Finkelstein JL et al. Iron-biofortified pearl millet improves iron status in adolescents in India: a randomized trial 2015;145(7):1576–1581. J Nutr. 2015.

Randomized trial on whether iron-biofortified pearl millet improves iron status in adolescents in India.

[1495] Devi PB et al. Health benefits of finger millet (Eleusine coracana L.) polyphenols and dietary fiber: a review2014;51(6):1021–1040. J Food Sci Technol. Link

The growing public awareness of nutrition and health care research substantiates the potential of phytochemicals such as polyphenols and dietary fiber on their health beneficial properties. Hence, there is in need to identify newer sources of neutraceuticals and other natural and nutritional materials with the desirable functional characteristics. Finger millet (Eleusine coracana), one of the minor cereals, is known for several health benefits and some of the health benefits are attributed to its polyphenol and dietary fiber contents. It is an important staple food in India for people of low income groups. Nutritionally, its importance is well recognised because of its high content of calcium (0.38\%), dietary fiber (18\%) and phenolic compounds (0.3-3\%). They are also recognized for their health beneficial effects, such as anti-diabetic, anti-tumerogenic, atherosclerogenic effects, antioxidant and antimicrobial properties.

[1496] Gaitan E et al. Goitrogenic effects of millet in iodine-deficient populations 1989. J Clin Endocrinol Metab. 1989.

Study of the goitrogenic effects of millet in iodine-deficient populations.

[1497] Anitha S et al. Millets can have a major impact on improving iron status, hemoglobin level, and in reducing iron deficiency anemia — a systematic review and meta-analysis 2022;8:725529. Front Nutr. 2022. Link

Systematic review and meta-analysis examining the impact of millets on iron status, hemoglobin level, and iron deficiency anemia. Across 19 studies in anaemic individuals, regular millet consumption (21 days to 4.5 years) significantly increased hemoglobin by about 13.2%, versus only ~2.7% on regular diets. In-vitro studies indicated that traditional processing (fermentation, germination) markedly improved iron bioavailability. (Note: the source was published in 2021.)

[1498] . ICRISAT2023 (UN International Year of Millets). Millets: nutricereals for climate-resilient food systems. Link

ICRISAT document presenting millets as nutricereals for climate-resilient food systems, tied to the UN International Year of Millets.

[1499] Hithamani G, Srinivasan K. Bioaccessibility of polyphenols from selected cereal grains and legumes 2014. Food Chem. 2014.

Food-chemistry study of the bioaccessibility of polyphenols from selected cereal grains and legumes.

[1501] Bressani R. Amaranth: composition, properties and applications of a rediscovered food crop 1989;5(1):13–38. Food Rev Int. 1989.

Review article on the composition, properties and applications of amaranth as a rediscovered food crop.

[1502] Berghofer E, Schoenlechner R. Grain amaranth: gluten-free flour for celiac patients 2003. Adv Exp Med Biol. 2003.

Paper on grain amaranth as a gluten-free flour for celiac patients.

[1503] Rastrelli L et al. Squalene content of amaranth seed oil 1996. J Agric Food Chem. 1996.

Food-chemistry article on the squalene content of amaranth seed oil.

[1504] Caselato-Sousa VM, Amaya-Farfán J. State of knowledge on amaranth grain: a comprehensive review2012;77(4):R93–R104. J Food Sci. Link

Amaranth grain is a highly nutritional pseudocereal with a superior amount of proteins when compared to true cereals. It is a reasonably well-balanced food with functional properties that have been shown to provide medicinal benefits. The health benefits attributed include decreasing plasma cholesterol levels, stimulating the immune system, exerting an antitumor activity, reducing blood glucose levels and improving conditions of hypertension and anemia. In addition, it has been reported to possess anti-allergic and antioxidant activities. The present article provides a comprehensive overview of amaranth grain that focuses on recent research reporting its use in the clinical practice and its possible benefits to human health.

[1505] Klimczak I et al. Polyphenol profile in amaranth seeds and sprouts 2002. Acta Sci Pol Technol Aliment. 2002.

Study of the polyphenol profile in amaranth seeds and sprouts.

[1506] Bermudez-Soto MJ et al. In vitro fermentation of amaranth dietary fiber 2012. Food Funct. 2012.

In vitro fermentation study of amaranth dietary fiber.

[1507] Sanz-Penella JM et al. Bread containing amaranth flour fortifies iron and bioactive compounds 2013. LWT-Food Sci Technol. 2013.

Study on bread containing amaranth flour fortifying iron and bioactive compounds.

[1508] Bauer A et al. Lacto-fermented amaranth: bioactivity and microbiota modulation 2022. Front Nutr. 2022.

Study on lacto-fermented amaranth, its bioactivity and microbiota modulation.

[1510] Sofi F et al. Effects of short-term consumption of bread obtained by an old Italian grain variety on lipid, inflammatory and hemorheological variables: an intervention study 2014. J Med Food. 2014. Link

Intervention study in 20 healthy subjects examining the effect of short-term consumption of bread made from an old Italian (Tuscan) grain variety on lipid, inflammatory and hemorheological variables. Participants consumed 150 g/day of the test bread for 10 weeks and then the same amount of commercial bread (control). The test period significantly improved total cholesterol (about 211 to 197 mg/dL) and LDL cholesterol. (Note: by DOI/publication the source is from 2010.)

[1511] Sofi F et al. Effect of Khorasan wheat consumption on quality of life and inflammation in IBS patients: a randomized, double-blind cross-over trial2014;111(11):1992–1999. Br J Nutr. 1992. Link

The aim of the present study was to examine the effect of a replacement diet with organic, semi-whole-grain products derived from Triticum turgidum subsp. turanicum (ancient) wheat on irritable bowel syndrome (IBS) symptoms and inflammatory/biochemical parameters. A double-blinded randomised cross-over trial was performed using twenty participants (thirteen females and seven males, aged 18-59 years) classified as having moderate IBS. Participants received products (bread, pasta, biscuits and crackers) made either from ancient or modern wheat for 6 weeks in a random order. Symptoms due to IBS were evaluated using two questionnaires, which were compiled both at baseline and on a weekly basis during the intervention period. Blood analyses were carried out at the beginning and end of each respective intervention period. During the intervention period with ancient wheat products, patients experienced a significant decrease in the severity of IBS symptoms, such as abdominal pain (P< 0·0001), bloating (P= 0·004), satisfaction with stool consistency (P< 0·001) and tiredness (P< 0·0001).

[1512] Baldi S et al. Effect of ancient Khorasan wheat on gut microbiota, inflammation, and short-chain fatty acid production in healthy adults 2022. Nutrients. 2022.

Study on the effect of ancient Khorasan wheat on gut microbiota, inflammation, and short-chain fatty acid production in healthy adults.

[1513] Dinu M et al. Ancient wheat species and human health: biochemical and clinical implications2018. J Nutr Biochem. Link

Wheat is the major staple food in many diets. Based on the increase in worldwide mortality attributable to diet-related chronic diseases, there is an increasing interest in identifying wheat species with greater health potential, more specifically for improved anti-oxidant and anti-inflammatory properties. In particular, ancient varieties (defined as those species that have remained unchanged over the last hundred years) are gaining interest since several studies suggested that they present a healthier nutritional profile than modern wheats. This manuscript reviews the nutritional value and health benefits of ancient wheats varieties, providing a summary of all in vitro, ex vivo, animal and human studies that have thus far been published. Differences in chemical composition, and biochemical and clinical implications of emmer, einkorn, spelt, khorasan and various regional Italian varieties are discussed. Although many studies based on in vitro analyses of grain components provide support to the premise of a healthier nutritional and functional potential of ancient wheat, other in vitro studies performed are not in support of an improved potential of ancient varieties.

[1514] Whittaker A et al. An organic Khorasan wheat-based replacement diet improves risk profile of patients with acute coronary syndrome: a RCT 2015. Nutr Metab Cardiovasc Dis. 2015. Link

Randomized, double-blind crossover trial in 22 acute coronary syndrome (ACS) patients examining whether a replacement diet substituting all other cereal grains with products made from organic Khorasan wheat (kamut) provides additive protection compared with a similar diet using modern wheat. The study focused on lipid, oxidative and inflammatory risk factors. The Khorasan wheat-based diet favourably improved the patients' risk profile.

[1515] Carnevale R et al. Ancient Khorasan wheat reduces oxidative stress in patients with NAFLD 2022. Eur J Nutr. 2022.

Study on whether ancient Khorasan wheat reduces oxidative stress in patients with NAFLD.

[1516] Damen B et al. Arabinoxylans and arabinoxylan-oligosaccharides: structure, prebiotic potential 2011. J Agric Food Chem. 2011.

Review article on the structure and prebiotic potential of arabinoxylans and arabinoxylan-oligosaccharides.

[1517] . Coeliac UKPosition statement. KAMUT (Khorasan wheat) is NOT gluten-free. Link

Coeliac UK position statement that KAMUT (Khorasan wheat) is NOT gluten-free.

[1519] Englyst HN, Kingman SM, Cummings JH. Classification and measurement of nutritionally important starch fractions1992;46 Suppl 2:S33–S50. Eur J Clin Nutr. Link

For nutritional purposes, starch in foods may be classified into rapidly digestible starch (RDS), slowly digestible starch (SDS) and resistant starch (RS). RS may be further divided into three categories according to the reason for resistance to digestion. A method is reported for the measurement of total starch, RDS, SDS, RS and three RS fractions in starchy foods, using controlled enzymic hydrolysis with pancreatin and amyloglucosidase. The released glucose is measured by colorimetry, using a glucose oxidase kit. Values for RDS and SDS in foods obtained by the method reflect the rate of starch digestion in vivo. Values for RS are similar to the amounts of starch escaping digestion in the small intestine of ileostomates, and are a guide to the amounts of starch likely to enter the colon for fermentation.

[1520] Walker AW et al. Dominant and diet-responsive groups of bacteria within the human colonic microbiota2011;5(2):220–230. ISME J. Link

The populations of dominant species within the human colonic microbiota can potentially be modified by dietary intake with consequences for health. Here we examined the influence of precisely controlled diets in 14 overweight men. Volunteers were provided successively with a control diet, diets high in resistant starch (RS) or non-starch polysaccharides (NSPs) and a reduced carbohydrate weight loss (WL) diet, over 10 weeks. Analysis of 16S rRNA sequences in stool samples of six volunteers detected 320 phylotypes (defined at >98\% identity) of which 26, including 19 cultured species, each accounted for >1\% of sequences. Although samples clustered more strongly by individual than by diet, time courses obtained by targeted qPCR revealed that 'blooms' in specific bacterial groups occurred rapidly after a dietary change. These were rapidly reversed by the subsequent diet.

[1522] Bodinham CL et al. Efficacy of increased resistant starch consumption in human type 2 diabetes2014;3(2):75–84. Endocr Connect. Link

Human study (Endocr Connect) on the efficacy of increased resistant starch consumption in human type 2 diabetes.

[1523] Li H et al. Resistant starch intake facilitates weight loss in humans by reshaping the gut microbiota2024. Nat Metab. Link

Emerging evidence suggests that modulation of gut microbiota by dietary fibre may offer solutions for metabolic disorders. In a randomized placebo-controlled crossover design trial (ChiCTR-TTRCC-13003333) in 37 participants with overweight or obesity, we test whether resistant starch (RS) as a dietary supplement influences obesity-related outcomes. Here, we show that RS supplementation for 8 weeks can help to achieve weight loss (mean -2.8 kg) and improve insulin resistance in individuals with excess body weight. The benefits of RS are associated with changes in gut microbiota composition. Supplementation with Bifidobacterium adolescentis, a species that is markedly associated with the alleviation of obesity in the study participants, protects male mice from diet-induced obesity. Mechanistically, the RS-induced changes in the gut microbiota alter the bile acid profile, reduce inflammation by restoring the intestinal barrier and inhibit lipid absorption.

[1524] Bendiks ZA et al. Resistant starch type 4 and gut microbiota2020. J Nutr Biochem. Link

Resistant starch type 2 (RS2), a dietary fiber comprised solely of glucose, has been extensively studied in clinical trials and animal models for its capacity to improve metabolic and systemic health. Because the health modulatory effects of RS2 and other dietary fibers are thought to occur through modification of the gut microbiome, those studies frequently include assessments of RS2-mediated changes to intestinal microbial composition and function. In this review, we identify the conserved responses of the gut microbiome among 13 human and 35 animal RS2 intervention studies. Consistent outcomes of RS2 interventions include reductions in bacterial α-diversity; increased production of lumenal short-chain fatty acids; and enrichment of Ruminococcus bromii, Bifidobacterium adolescentis, and other gut taxa. Different taxa are usually responsive in animal models, and many RS2-mediated changes to the gut microbiome vary within and between studies. The root causes for this variation are examined with regard to methodological and analytical differences, host genetics and age, species differences (eg, human, animal), health status, intervention dose and duration, and baseline microbial composition.

[1525] Ze X et al. Ruminococcus bromii is a keystone species for the degradation of resistant starch in the human colon2012. ISME J. Link

The release of energy from particulate substrates such as dietary fiber and resistant starch (RS) in the human colon may depend on the presence of specialist primary degraders (or 'keystone species') within the microbial community. We have explored the roles of four dominant amylolytic bacteria found in the human colon in the degradation and utilization of resistant starches. Eubacterium rectale and Bacteroides thetaiotaomicron showed limited ability to utilize RS2- and RS3-resistant starches by comparison with Bifidobacterium adolescentis and Ruminococcus bromii. In co-culture, however, R. bromii proved unique in stimulating RS2 and RS3 utilization by the other three bacterial species, even in a medium that does not permit growth of R. bromii itself. Having previously demonstrated low RS3 fermentation in vivo in two individuals with undetectable populations of R. bromii-related bacteria, we show here that supplementation of mixed fecal bacteria from one of these volunteers with R. bromii, but not with the other three species, greatly enhanced the extent of RS3 fermentation in vitro. This argues strongly that R. bromii has a pivotal role in fermentation of RS3 in the human large intestine, and that variation in the occurrence of this species and its close relatives may be a primary cause of variable energy recovery from this important component of the diet.

[1526] DeMartino P, Cockburn DW. Resistant starch: impact on the gut microbiome and health2020. Curr Opin Biotechnol. Link

Resistant starch has received a lot of attention for its potential to exert a healthy impact on the gut and certain members of its resident microbiota, particularly through enhanced butyrate production. However, resistant starch is a broad category that encompasses several structurally different starches. While all resist digestion by human enzymes, they differ in their effects on the microbiota. Individual variation in microbiota composition also has a substantial influence on butyrate production. Research on this interaction between resistant starch and the microbiota is using in vitro fermentations, cross-over design clinical trials and mouse studies with isotopically labeled starch. These studies are demonstrating that more personalized approaches are needed for finding resistant starch or other fiber that will promote a healthy gut.

[1530] Raben A et al. Resistant starch: the effect on postprandial glycemia, hormonal response, and satiety1994;60(4):544–551. Am J Clin Nutr. Link

The effect of resistant starch (RS) on postprandial plasma concentrations of glucose, lipids, and hormones, and on subjective satiety and palatability ratings was investigated in 10 healthy, normal-weight, young males. The test meals consisted of 50 g pregelatinized starch (0\% RS) (S) or 50 g raw potato starch (54\% RS) (R) together with 500 g artificially sweetened syrup. After the R meal postprandial plasma concentrations of glucose, lactate, insulin, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1, and epinephrine were significantly lower compared with after the S meal. Moreover, subjective scores for satiety and fullness were significantly lower after the R meal than after the S meal. Differences in GIP, texture, and palatability may have been involved in these findings. In conclusion, the replacement of digestible starch with RS resulted in significant reductions in postprandial glycemia and insulinemia, and in the subjective sensations of satiety.

[1531] Bird AR et al. Resistant starch, large bowel fermentation and a broader perspective of prebiotics and probiotics2010. Beneficial Microbes. Link

The metabolic end products of the large bowel microbiota contribute significantly to human health. After weaning to solid foods, some of the most important of these are the short chain fatty acids (SCFA) produced by the fermentation of undigested dietary components and endogenous secretions. The main SCFA are acetate, propionate and butyrate which have numerous documented effects promoting large bowel function. Of the major acids, butyrate seems especially important. It is a major metabolic fuel for colonocytes and promotes a normal phenotype in these cells, potentially lowering the risk of diseases such as colo-rectal cancer. Imbalances in the microbiota are thought to predispose to large bowel dysfunction and probiotics are being developed to correct this.

[1532] Ze X et al. Ruminococcus bromii is a keystone species for the degradation of resistant starch in the human colon2012;6(8):1535–1543. ISME J. Link

[1533] Lockyer S, Nugent AP. Health effects of resistant starch2017;42(1):10–41. Nutr Bull. Link

Review of the health effects of resistant starch (RS). The authors explain that RS is a form of starch resistant to small-intestinal digestion, classified as dietary fibre and categorized into five types (RS1-RS5); some occur naturally (bananas, potatoes, grains, legumes) and some are produced commercially. RS increases short-chain fatty acid production in the gut, and many human studies have addressed its health effects, but further research is needed in most areas to establish significant population-relevant benefits.

[1534] Patterson MA et al. Resistant starch content in foods commonly consumed in the United States: a narrative review2020. J Acad Nutr Diet. Link

Resistant starch (RS; types 1 to 5) cannot be digested in the small intestine and thus enters the colon intact, with some types capable of being fermented by gut microbes. As a fiber, types 1, 2, 3, and 5 are found naturally in foods, while types 2, 3, and 4 can be added to foods as a functional ingredient. This narrative review identifies RS content in whole foods commonly consumed in the United States. Scientific databases (n=3) were searched by two independent researchers. Ninety-four peer-reviewed articles published between 1982 and September 2018 were selected in which the RS was quantified and the food preparation method before analysis was suitable for consumption. The RS from each food item was adjusted for moisture if the RS value was provided as percent dry weight.

[1535] . Food Standards Agency2022. Cooked rice — fried rice syndrome (Bacillus cereus) safety guidance. Link

Food Standards Agency safety guidance on cooked rice and fried rice syndrome (Bacillus cereus).

[1536] . EFSA BIOHAZ Panel2016. Update of the risk assessment of Bacillus cereus group bacteria in foodstuffs. Link

EFSA BIOHAZ Panel's updated risk assessment of Bacillus cereus group bacteria in foodstuffs.

[1537] Sugihara TF, Kline L. Microorganisms of the San Francisco sour dough bread process1971. Appl Microbiol. Link

Two hundred isolates from San Francisco sour dough French bread fermentations (40 from each of five different bakeries) were screened by fermentation tests and for their ability to grow in the presence of cycloheximide (Actidione). All of the isolates from four of the bakeries and 70\% of those from the fifth were unable to utilize maltose but grew well on other sugars, even in the presence of cycloheximide. The remaining few isolates from the fifth bakery utilized maltose but not galactose and were inhibited by cycloheximide. No bakers' yeast types were found. Sixteen of the maltose-negative and five of the galactose-negative isolates were subjected to more rigorous taxonomic procedures. All of the maltose-negative isolates were identified as asporogenous strains of Saccharomyces exiguus (Torulopsis holmii) and the galactose-negative ones, as S. inusitatus.

[1538] Larsson M, Sandberg AS. Phytate degradation in sourdough bread1996. Cereal Chem. Link

Cereal-chemistry study of phytate degradation in sourdough bread.

[1539] Walton GE et al. A randomised, double-blind, placebo-controlled cross-over study to determine the gastrointestinal effects of consumption of arabinoxylan-oligosaccharides enriched bread2012;11:36. Nutr J. Link

BACKGROUND: Prebiotics are food ingredients, usually non-digestible oligosaccharides, that are selectively fermented by populations of beneficial gut bacteria. Endoxylanases, altering the naturally present cereal arabinoxylans, are commonly used in the bread industry to improve dough and bread characteristics. Recently, an in situ method has been developed to produce arabinoxylan-oligosaccharides (AXOS) at high levels in breads through the use of a thermophilic endoxylanase. AXOS have demonstrated potentially prebiotic properties in that they have been observed to lead to beneficial shifts in the microbiota in vitro and in murine, poultry and human studies. METHODS: A double-blind, placebo controlled human intervention study was undertaken with 40 healthy adult volunteers to assess the impact of consumption of breads with in situ produced AXOS (containing 2.2 g AXOS) compared to non-endoxylanase treated breads. Volatile fatty acid concentrations in faeces were assessed and fluorescence in situ hybridisation was used to assess changes in gut microbial groups.

[1541] Pomp ER et al. Sourdough fermentation reduces FODMAP and improves tolerance in NCGS patients2020. Nutrients. Link

Study (Nutrients) reporting that sourdough fermentation reduces FODMAP content and improves tolerance in NCGS patients.

[1542] Gobbetti M et al. How the sourdough may affect the functional features of leavened baked goods2014. Food Microbiol. Link

Sourdough fermentation is one of the oldest food biotechnologies, which has been studied and recently rediscovered for its effect on the sensory, structural, nutritional and shelf life properties of leavened baked goods. Acidification, proteolysis and activation of a number of enzymes as well as the synthesis of microbial metabolites cause several changes during sourdough fermentation, which affect the dough and baked good matrix, and influence the nutritional/functional quality. Currently, the literature is particularly rich of results, which show how the sourdough fermentation may affect the functional features of leavened baked goods. In the form of pre-treating raw materials, fermentation through sourdough may stabilize or to increase the functional value of bran fractions and wheat germ. Sourdough fermentation may decrease the glycaemic response of baked goods, improve the properties and bioavailability of dietary fibre complex and phytochemicals, and may increase the uptake of minerals. Microbial metabolism during sourdough fermentation may also produce new nutritionally active compounds, such as peptides and amino acid derivatives (e.g., γ-amino butyric acid) with various functionalities, and potentially prebiotic exo-polysaccharides.

[1543] Di Cagno R et al. Sourdough lactic acid bacteria reduce ATI activity 2010. Appl Environ Microbiol. 2010.

Study showing that sourdough lactic acid bacteria reduce ATI (amylase-trypsin inhibitor) activity.

[1544] Lopez HW et al. Phytate degradation and mineral bioavailability in sourdough bread2003. J Agric Food Chem. Link

Study (J Agric Food Chem) on phytate degradation and mineral bioavailability in sourdough bread.

[1546] Hu C et al. 2003 — Black rice extracts: antioxidant and antiproliferative activities. J Agric Food Chem. Link

Food-chemistry article on the antioxidant and antiproliferative activities of black rice extracts.

[1547] Wallace TC et al. 2016 — Anthocyanins and health: a systematic review and meta-analysis. Crit Rev Food Sci Nutr. Link

Systematic review and meta-analysis (Crit Rev Food Sci Nutr) on anthocyanins and health.

[1548] Czank C et al. 2013 — Human metabolism and elimination of cyanidin-3-glucoside. Am J Clin Nutr. Link

Study of the human metabolism and elimination of cyanidin-3-glucoside.

[1549] Callcott ET et al. 2018 — Pigmented rice-derived phenolic compounds reduce biomarkers of oxidative stress and inflammation in human subjects. Br J Nutr. Link

Rice-derived polyphenols have been demonstrated to alleviate obesity-related oxidative stress and inflammation. The aim of the study was to investigate if coloured rice polyphenol extracts (PE) reduce malondialdehyde, interleukin-6 and tumour necrosis factor-α (TNF-α) levels in obese individuals ex vivo. Malondialdehyde and pro-inflammatory cytokines were quantified using high-performance liquid chromatography and flow cytometry respectively. Fasting blood samples were treated with PE from three coloured rice varieties (purple, red and brown rice) at varying concentrations (10, 20, 50, 100, 200 and 500 μg mL-1). PE treatment demonstrated a dose-dependent reduction in malondialdehyde and TNF-α levels. Purple PE reduced plasma malondialdehyde concentration by 59\% compared to red (21\%) and brown (25.5\%) rice PE.

[1550] . Cicero AF, Gaddi A2001 — Rice bran oil and γ-oryzanol in lipid metabolism. Phytother Res. Link

Diet is the first (and sometimes the only) therapeutic approach to hyperlipoproteinaemias. Rice bran oil and its main components (unsaturated fatty acids, triterpene alcohols, phytosterols, tocotrienols, alpha-tocopherol) have demonstrated an ability to improve the plasma lipid pattern of rodents, rabbits, non-human primates and humans, reducing total plasma cholesterol and triglyceride concentration and increasing the high density lipoprotein cholesterol level. Other potential properties of rice bran oil and gamma-oryzanol, studied both in vitro and in animal models, include modulation of pituitary secretion, inhibition of gastric acid secretion, antioxidant action and inhibition of platelet aggregation. This paper reviews the available data on the pharmacology and toxicology of rice bran oil and its main components with particular attention to those studies relating to plasma lipid altering effects.

[1551] Sengupta MK et al. 2006 — Arsenic burden of cooked rice. Environ Sci Technol. Link

Arsenic contamination of rice by irrigation with contaminated groundwater and secondarily increased soil arsenic compounds the arsenic burden of populations dependent on subsistence rice-diets. The arsenic concentration of cooked rice is known to increase with the arsenic concentration of the cooking water but the effects of cooking methods have not been defined. We tested the three major rice cooking procedures followed globally. Using low-arsenic water (As < 3 microg/L), the traditional method of the Indian subcontinent (wash until clear; cook with rice: water::1:6; discard excess water) removed up to 57\% of the arsenic from rice containing arsenic 203-540 microg/kg. Approximately half of the arsenic was lost in the wash water, half in the discard water. A simple inexpensive rice cooker based on this method has been designed and used for this purpose.

[1552] . EFSA Panel CONTAM 2014 — Dietary exposure to inorganic arsenic in the European population. . 2014. Link

EFSA CONTAM Panel assessment of dietary exposure to inorganic arsenic in the European population.

[1553] Sui X et al. 2014 — Effects of thermal processing on anthocyanin stability. Food Chem. Link

Study (Food Chem) on the effects of thermal processing on anthocyanin stability.

[1554] . USDA FoodData Central #169757 (Rice, black, cooked). Link

USDA FoodData Central entry for cooked black rice (#169757).

[1555] . Monash University FODMAP App — black rice: low-FODMAP up to 1 cup cooked. Link

Monash University FODMAP App entry listing black rice as low-FODMAP up to 1 cup cooked.

[1556] Geisslitz S et al. Comparative quantitative LC-MS/MS analysis of 13 amylase/trypsin inhibitors in ancient and modern Triticum species2020;10(1):14570. Sci Rep. Link

Amylase/trypsin inhibitors (ATIs) are major wheat allergens and they are also implicated in causing non-celiac gluten sensitivity and worsening other inflammatory conditions. With only few studies on ATI contents in different Triticum species available so far, we developed a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method based on stable isotope dilution assays to quantitate the 13 most important ATIs in a well-defined sample set of eight cultivars of common wheat and durum wheat (modern species), as well as spelt, emmer and einkorn (ancient species) grown at three locations in Germany, respectively. Only few ATIs with low contents were detected in einkorn. In contrast, spelt had the highest total ATI contents. Emmer and common wheat had similar total ATI contents, with durum wheat having lower contents than common wheat. Due to the lack of correlation, it was not possible to estimate ATI contents based on crude protein contents.

[1557] Geisslitz S et al. Wheat ATIs: characteristics and role in human disease2019;6:153. Front Nutr. Link

Review article (Front Nutr) on the characteristics of wheat amylase-trypsin inhibitors (ATIs) and their role in human disease.

[1558] Spaenij-Dekking L et al. Natural variation in toxicity of wheat: potential for selection of nontoxic varieties for celiac disease patients2005;129(3):797–806. Gastroenterology. Link

BACKGROUND \& AIMS: Celiac disease (CD) is an intestinal disorder caused by T-cell responses to peptides derived from the gluten proteins present in wheat. Such peptides have been found both in the gliadin and glutenin proteins in gluten. The only cure for CD is a lifelong gluten-free diet. It is unknown, however, if all wheat varieties are equally harmful for patients. We investigated whether wheat varieties exist with a natural low number of T-cell-stimulatory epitopes. METHODS: Gluten proteins present in public databases were analyzed for the presence of T-cell-stimulatory sequences.

[1559] Andersson AAM et al. Contents of dietary fibre components and their relation to associated bioactive components in whole grain wheat2013;136(3-4):1243–1248. Food Chem. Link

A large and diverse material collection of whole grain wheat samples (n=129) was analysed for total dietary fibre (TDF) content and composition, including fructan (11.5-15.5\%). Correlations between the dietary fibre components, associated bioactive components (e.g. tocols, sterols, phenolic acids and folates) and agronomic properties previously determined on the same samples were found with multivariate analysis (PCA). Samples from the same countries had similar characteristics. The first PC described variation in components concentrated in the starchy endosperm (e.g. starch, β-glucan and fructan) and the dietary fibre components concentrated in the bran (e.g. TDF, arabinoxylan and cellulose). The second PC described the variation in kernel weight and other bran components such as alkylresorcinols, tocols and sterols.

[1560] François IE et al. Effects of a wheat bran arabinoxylan oligosaccharide on human gut microbiota2012;108(12):2229–2242. Br J Nutr. Link

Study on the effects of a wheat bran arabinoxylan oligosaccharide on the human gut microbiota.

[1561] Lecerf JM et al. Xylo-oligosaccharide (XOS) in combination with inulin modulates both the intestinal environment and immune status in healthy subjects2012;108(10):1847–1858. Br J Nutr. Link

The purpose of the present study was to establish the prebiotic effect of a new xylo-oligosaccharide (XOS) and of an inulin-and-XOS mixture (INU-XOS) and to determine their effect on endotoxaemia (lipopolysaccharides (LPS)) and immune parameters. In this randomised, parallel, placebo-controlled, double-blind study, sixty healthy volunteers were randomly assigned to three groups, receiving either 5 g XOS, INU-XOS (3 g inulin +1 g XOS) or an equivalent weight of wheat maltodextrin (placebo) during 4 weeks. Faecal samples were collected to assess the effects of these products on microbiota, as well as SCFA composition, enzymatic activities and secretory IgA production. Circulating LPS was measured in plasma samples, and whole blood was incubated with LPS to measure cytokine expression. Consumption of XOS alone increased the faecal concentrations of Bifidobacterium and butyrate and activities of α-glucosidase and β-glucuronidase, while decreasing the concentrations of acetate and p-cresol. Consumption of XOS in combination with inulin did not decrease the concentrations of acetate and p-cresol, but increased in addition the faecal concentrations of total SCFA and propionate.

[1562] Vitaglione P et al. Cereal dietary fibre: a natural functional ingredient to deliver phenolic compounds into the gut2008;19(9):451–463. Trends Food Sci Technol. Link

Review proposing that cereal dietary fibre can act as a natural functional ingredient to deliver phenolic compounds into the gut. The authors start from the chemical structure, bioavailability and biological significance of the antioxidant component of cereal fibre. The paper advances the hypothesis that slow and continuous release of fibre-bound antioxidants in the gut determines the associated health benefits.

[1563] Loponen J, Gänzle MG. Use of sourdough in low-FODMAP baking2018;7(7):96. Foods. Link

A low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet allows most irritable bowel syndrome (IBS) patients to manage their gastrointestinal symptoms by avoiding FODMAP-containing foods, such as onions, pulses, and products made from wheat or rye. The downside of a low FODMAP diet is the reduced intake of dietary fiber. Applying sourdoughs\—with specific FODMAP-targeting metabolic properties\—to wholegrain bread making can help to remarkably reduce the content of FODMAPs in bread without affecting the content of the slowly fermented and well-tolerated dietary fiber. In this review, we outline the metabolism of FODMAPs in conventional sourdoughs and outline concepts related to fructan and mannitol metabolism that allow development of low FODMAP sourdough bread. We also summarize clinical studies where low FODMAP but high fiber, rye sourdough bread was tested for its effects on gut fermentation and gastrointestinal symptoms with very promising results. The sourdough bread-making process offers a means to develop natural and fiber-rich low FODMAP bakery products for IBS patients and thereby help them to increase their dietary fiber intake.

[1565] Sofi F et al. Effect ofsubsp. turanicum wheat on irritable bowel syndrome: a double-blinded randomised dietary intervention trial. Br J Nutr 2014;111(11):1992–1999. Triticum turgidum. 2014. Link

[1566] Whittaker A et al. A khorasan wheat-based replacement diet improves risk profile of patients with type 2 diabetes mellitus: a randomized crossover trial2017;56(3):1191–1200. Eur J Nutr. Link

PURPOSES: The aim of the present study was to examine whether a replacement diet with products made with organic ancient khorasan wheat could provide additive protective effects in reducing glucose, insulin, lipid and inflammatory risk factors, and in restoring blood redox balance in type 2 diabetes mellitus (T2DM) patients compared to diet with product made with modern organic wheat. METHODS: We conducted a randomized, double-blinded crossover trial with two intervention phases on 21 T2DM patients (14 females, 7 males). The participants were assigned to consume products (bread, pasta, crackers and biscuits) made using semi-whole flour from organic wheat that was either from ancient khorasan wheat or modern control wheat for 8 weeks in a random order. An 8-week washout period was implemented between the interventions. Laboratory analyses were performed both at the beginning and at the end of each intervention phase. RESULTS: The metabolic risk profile improved only after the khorasan intervention period, as measured by a reduction in total and LDL cholesterol (mean reduction: -3.7 and -3.4 \%, respectively), insulin (-16.3 \%) and blood glucose (-9.1 \%).

[1567] Geisslitz S et al. Targeted LC-MS/MS reveals similar contents of α-amylase/trypsin-inhibitors as putative triggers of nonceliac gluten sensitivity in all wheat species except einkorn2018;66(46):12395–12403. J Agric Food Chem. Link

Amylase/trypsin-inhibitors (ATIs) are putative triggers of nonceliac gluten sensitivity, but contents of ATIs in different wheat species were not available. Therefore, the predominant ATIs 0.19 + 0.53, 0.28, CM2, CM3, and CM16 in eight cultivars each of common wheat, durum wheat, spelt, emmer, and einkorn grown under the same environmental conditions were quantitated by targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) and stable isotope dilution assays using specific marker peptides as internal standards. The results were compared to a label-free untargeted LC-MS/MS analysis, in which protein concentrations were determined by intensity based absolute quantitation. Both approaches yielded similar results. Spelt and emmer had higher ATI contents than common wheat, with durum wheat in between. Only three of eight einkorn cultivars contained ATIs in very low concentrations.

[1568] Hidalgo A, Brandolini A. Lipid components in einkorn (Triticum monococcum L.) and other Triticum species 2013;57(3):454–457. J Cereal Sci. 2013.

Cereal-science article on the lipid components in einkorn (Triticum monococcum L.) and other Triticum species.

[1569] Abdel-Aal ES et al. Identification and quantification of seed carotenoids in selected wheat species2007;55(3):787–794. J Agric Food Chem. Link

Study identifying and quantifying seed carotenoids in selected wheat species.

[1570] Mohn ES et al. Lutein and cognition across the lifespan2018;9(5):671–688. Adv Nutr. Link

Review article on lutein and cognition across the lifespan.

[1571] Schlemmer U et al. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis2009;53(S2):S330–S375. Mol Nutr Food Res. Link

The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described.

[1574] Min B et al. Phytochemicals and antioxidant capacities in rice brans of different color2014;79(7):C1255–C1264. J Food Sci. Link

Study of the phytochemicals and antioxidant capacities in rice brans of different color.

[1575] Massaretto IL et al. Phenolic compounds in raw and cooked rice (Oryza sativa L.) and their inhibitory effect on the activity of angiotensin I-converting enzyme2011;54(2):236–240. J Cereal Sci. Link

Study examining the phenolic compounds in raw and cooked rice (Oryza sativa L.) and their inhibitory effect on angiotensin I-converting enzyme (ACE) activity. Cooking substantially reduced the average total phenolic content of the pigmented rice group by about 50% (from roughly 409.7 to 202.6 mg ferulic acid eq./100 g). The findings point to a potential blood-pressure-lowering (ACE-inhibitory) role of rice phenolics.

[1576] Bumrungpert A et al. Rice bran oil containing gamma-oryzanol improves lipid profiles and antioxidant status in hyperlipidemic subjects: a randomized double-blind controlled trial2019;25(3):353–358. J Altern Complement Med. Link

Randomized double-blind controlled trial of rice bran oil containing gamma-oryzanol for improving lipid profiles and antioxidant status in hyperlipidemic subjects.

[1577] Saenkod C et al. Anti-oxidative biochemical properties of extracts from some Chinese and Thai rice varieties 2013;7:300–305. African J Food Sci. 2013. Link

Saenkod et al. (African J Food Sci 2013) evaluated total phenolic content (TPC), total flavonoid content (TFC) and antioxidant activity of extracts from 8 Chinese and Thai rice varieties using water (25 C), hot water (50 C) and 70% ethanol extraction. The highest TPC, TFC and antioxidant activity were obtained with the 70% ethanol extracts, notably in the black Heimi and Jing Nian and the red Dok Kam and Niaow Deang varieties; phenolic and flavonoid content correlated with the colour of the rice.

[1578] Monagas M et al. Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites2010;1(3):233–253. Food Funct. Link

Flavan-3-ols, occurring in monomeric, as well as in oligomeric and polymeric forms (also known as condensed tannins or proanthocyanidins), are among the most abundant and bioactive dietary polyphenols, but their in vivo health effects in humans may be limited because of their recognition as xenobiotics. Bioavailability of flavan-3-ols is largely influenced by their degree of polymerization; while monomers are readily absorbed in the small intestine, oligomers and polymers need to be biotransformed by the colonic microbiota before absorption. Therefore, phenolic metabolites, rather than the original high molecular weight compounds found in foods, may be responsible for the health effects derived from flavan-3-ol consumption. Flavan-3-ol phenolic metabolites differ in structure, amount and excretion site. Phase II or tissular metabolites derived from the small intestine and hepatic metabolism are presented as conjugated derivatives (glucuronic acid or sulfate esters, methyl ether, or their combined forms) of monomeric flavan-3-ols and are preferentially eliminated in the bile, whereas microbial metabolites are rather simple conjugated lactones and phenolic acids that are largely excreted in urine. Although the colon is seen as an important organ for the metabolism of flavan-3-ols, the microbial catabolic pathways of these compounds are still under consideration, partly due to the lack of identification of bacteria with such capacity.

[1579] Gray PJ et al. Inorganic arsenic in rice and rice products on the United States market 2016;64(15):3025–3029. J Agric Food Chem. 2016.

Study of inorganic arsenic in rice and rice products on the United States market.

[1580] EFSA. Inorganic arsenic in food: dietary exposure assessment2014;12(3):3597. EFSA Journal. Link

EFSA dietary exposure assessment of inorganic arsenic in food.

[1581] Sumczynski D et al. Phenolic acids, anthocyanins, and antioxidant activity in pigmented rice2016;71(2):117–123. Plant Foods Hum Nutr. Link

Soluble-free, soluble-conjugated, insoluble-bound phenolics and antioxidant activity, flavonoid (TFC), proanthocyanidins (TPAC), anthocyanins and minerals of fifteen whole rice grains with different colors were investigated. Soluble-free protocatechuic and vanillic acids were only quantified in black rice, which had the most quantities. Non-pigmented rice had no detectable conjugated protocatechuic and 2,5-dihydroxybenzoic acids both of which were found in black and red rice, respectively. The main bound phenolic acids were ferulic and p-coumaric, as well as 2,5-dihydroxybenzoic in red rice and protocatechuic and vanillic acids in black rice. Soluble-conjugated phenolics, TFC, and anthocyanins were negatively correlated with L∗, b∗, C and H° values. TPAC was positively correlated with a∗ (P<0.01).

[1583] Qiu Y et al. Antioxidant properties of commercial wild rice and analysis of soluble and insoluble phenolic acids2010;121(1):140–147. Food Chem. Link

Study of the antioxidant properties of commercial wild rice and analysis of its soluble and insoluble phenolic acids.

[1584] Bunzel M et al. Diferulates as structural components in soluble and insoluble cereal dietary fibre 2001;81(7):653–660. J Sci Food Agric. 2001. Link

Bunzel et al. (J Sci Food Agric 2001) quantified dehydrodiferulic acids (diferulates) in soluble and insoluble dietary fibre isolated from whole grains of maize, wheat, spelt, rice, wild rice, barley, rye, oat and millet. The full spectrum of dehydrodiferulic acids (8-5'-, 8-8'-, 5-5'-, 8-O-4'- and 4-O-5'-coupled) was identified in insoluble fibre at total contents of 2.4-12.6 mg/g, whereas the same range occurred in soluble fibre only at much lower amounts of 40-230 ug/g; diferulates act as cross-linking structural components of cereal dietary fibre.

[1585] Surendiran G et al. Wild rice (Zizania palustris L.) prevents atherogenesis in LDL receptor knockout mice2013;230(2):284–292. Atherosclerosis. Link

OBJECTIVES: Dietary modifications including healthy eating constitute one of the first line strategies for prevention and treatment of cardiovascular disease (CVD) risk factors including high cholesterol and atherosclerosis. The purpose of the present study was to investigate the potential cardiovascular benefits of wild rice in male and female LDL-receptor-deficient (LDLr-KO) mice. METHODS: Wild rice was used to create a semi-synthetic diet containing approximately 60\% of total energy from carbohydrate. Two other experimental diets were similar in macronutrient composition, but containing either white rice or commercial carbohydrate sources. All diets were supplemented with 0.06\% (w/w) dietary cholesterol. The mice were divided into six experimental groups and fed with these diets over 24 weeks.

[1586] Han S et al. Wild rice ( L.) extract attenuates obesity and inflammation in high-fat-diet-fed mice. J Food Sci 2018;83(3):834–841. (Note: result based on Z. palustris L. extract — North American species, not the Asian Z. latifolia.)**. Zizania palustris. 2018.

Mouse study on the effect of wild rice (Zizania palustris L., North American species) extract on obesity and inflammation under a high-fat diet.

[1587] . USDAUSDA Agricultural Research Service. National Nutrient Database for Standard Reference — wild rice, cooked. Link

USDA Agricultural Research Service national nutrient database entry providing the nutrient composition of cooked wild rice.

[1588] Anishinaabe Manoomin (Wild Rice) — Slow Food Ark of Taste. Slow Food Foundation for Biodiversity. Link

Slow Food Foundation for Biodiversity Ark of Taste entry on Anishinaabe manoomin (wild rice) as a traditional food.

[1591] Stiemsma LT et al. Does Consumption of Fermented Foods Modify the Human Gut Microbiota?2020;150(7):1680–1692. J Nutr. 2020. Link

Review article (J Nutr) addressing whether consumption of fermented foods modifies the human gut microbiota.

[1592] Beganović J et al. Improved sauerkraut production with probiotic strain Lactobacillus plantarum L4 and Leuconostoc mesenteroides LMG 79542014;79(3):M531–M535. J Food Sci. Link

UNLABELLED: Probiotic strain Lactobacillus plantarum L4 and strain Leuconostoc mesenteroides LMG 7954 were applied for the controlled fermentation of cabbage heads. The parameters of the controlled and spontaneous fermentations, including antimicrobial effect of cabbage brines obtained at the end of both fermentations, were monitored. To check out the influence of starter culture strains, 10 randomly chosen lactic acid bacteria, isolated at the end of controlled cabbage heads fermentation were identified by API 50 CHL test, and the presence of the probiotic culture was confirmed by Pulsed Field Gel Electrophoresis. The starter cultures applied for cabbage heads fermentation allowed lowering of NaCl concentrations from 4.0\% to 2.5\% (w/v), considerably accelerated fermentation process by 14 d, and improved the product quality. The produced sauerkraut heads are considered probiotic product as viable probiotic cells count in final product was higher than 10(6) colony-forming units (CFU) per gram of product. PRACTICAL APPLICATION: The results of this research could be applied in the production of fermented cabbage heads with added functional (probiotic) value and with lower NaCl concentration with expected shortened fermentation time.

[1593] Nielsen ES et al. Lacto-fermented sauerkraut improves symptoms in IBS patients independent of product pasteurisation — a pilot study2018;9(10):5323–5335. Food Funct. Link

Lacto-fermented sauerkraut contains a natural variety of lactic acid bacteria (LAB) and has not previously been studied in the treatment of irritable bowel syndrome (IBS) patients. The present study investigated the effect of a daily lacto-fermented sauerkraut supplement in relation to IBS patients' gastrointestinal symptoms and gut microbiota composition. A randomized double-blinded intervention was conducted with 34 Norwegian IBS patients. The patients were consuming either pasteurized sauerkraut (PS; n = 15) or unpasteurized sauerkraut (UPS; n = 19) as a supplement to their daily diet for 6 weeks. The differences in change of symptoms were assessed using the questionnaire IBS-Symptom Severity Score (IBS-SSS) measured at the baseline, and at weeks 2, 4, 6 and 8 (follow-up). The gut microbiota composition was analysed using 16S rRNA gene amplicon sequencing of faecal samples from the baseline and week 6.

[1594] Han K et al. Comparison of fresh versus pasteurised sauerkraut on the human gut microbiota and serum short-chain fatty acids: a randomised crossover trial2025. Front Microbiol. Link

Randomised crossover clinical trial comparing fresh versus pasteurised sauerkraut on the human gut microbiota and serum short-chain fatty acids.

[1595] Cook J, Pringle J. The Method Taken for Preserving the Health of the Crew of His Majesty's Ship the Resolution1776. Phil Trans Royal Soc. Link

Cook and Pringle's 1776 historical Phil Trans Royal Soc account describing the method taken for preserving the health of HMS Resolution's crew.

[1596] Hill C et al. The International Scientific Association for Probiotics and Prebiotics consensus statement2014;11(8):506–514. Nat Rev Gastroenterol Hepatol. Link

An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.

[1597] Penas E et al. Health benefits of fermented vegetables and cereals 2017;6(8):65. Foods. 2017.

Review article in Foods (2017) on the health benefits of fermented vegetables and cereals.

[1598] McDonald LC et al. Acid tolerance of Leuconostoc mesenteroides and Lactobacillus plantarum1990;56(7):2120–2124. Appl Environ Microbiol. Link

In this study, we determined the internal cellular pH response of Leuconostoc mesenteroides and Lactobacillus plantarum to the external pH created by the microorganisms themselves or by lactic or acetic acids and their salts added to the growth medium. Growth of Leuconostoc mesenteroides stopped when its internal pH reached 5.4 to 5.7, and growth of L. plantarum stopped when its internal pH reached 4.6 to 4.8. Variation in growth medium composition or pH did not alter the growth-limiting internal pH reached by these microorganisms. L. plantarum maintained its pH gradient in the presence of either 160 mM sodium acetate or sodium lactate down to an external pH of 3.0 with either acid. In contrast, the DeltapH of Leuconostoc mesenteroides was zero at pH 4.0 with acetate and 5.0 with lactate. No differences were found between d-(-)- and l-(+)-lactic acid for the limiting internal pH for growth of either microorganism.

[1600] Nielsen ES et al. Lacto-fermented sauerkraut improves symptoms in IBS patients2018;9(10):5323–5335. Food Funct. Link

[1601] Marco ML et al. Health benefits of fermented foods: microbiota and beyond (ISAPP)2017;44:94–102. Curr Opin Biotechnol. 2017. Link

Fermented foods and beverages were among the first processed food products consumed by humans. The production of foods such as yogurt and cultured milk, wine and beer, sauerkraut and kimchi, and fermented sausage were initially valued because of their improved shelf life, safety, and organoleptic properties. It is increasingly understood that fermented foods can also have enhanced nutritional and functional properties due to transformation of substrates and formation of bioactive or bioavailable end-products. Many fermented foods also contain living microorganisms of which some are genetically similar to strains used as probiotics. Although only a limited number of clinical studies on fermented foods have been performed, there is evidence that these foods provide health benefits well-beyond the starting food materials.

[1602] Pérez-Díaz IM et al. Fermentation of cucumbers — review of the microbial ecology. USDA-ARS. Link

USDA-ARS review on the microbial ecology of cucumber fermentation.

[1603] Behera SS et al. Lactic acid fermentation of vegetables: a review 2018;58(15):2456–2470. Crit Rev Food Sci Nutr. 2018.

Review in Crit Rev Food Sci Nutr (2018) on the lactic acid fermentation of vegetables.

[1604] ISAPP. Fermented foods consensus statement2021. Nat Rev Gastroenterol Hepatol. Link

ISAPP (2021) consensus statement on fermented foods, published in Nat Rev Gastroenterol Hepatol.

[1605] Monash University FODMAP database. Pickled cucumber serving guide. Link

Monash University FODMAP database serving guide for pickled cucumber.

[1606] Park KY et al. Health benefits of kimchi (Korean fermented vegetables)2014;17(1):6–20. J Med Food. 2014. Link

Kimchi is a traditional Korean food manufactured by fermenting vegetables with probiotic lactic acid bacteria (LAB). Many bacteria are involved in the fermentation of kimchi, but LAB become dominant while the putrefactive bacteria are suppressed during salting of baechu cabbage and the fermentation. The addition of other subingredients and formation of fermentation byproducts of LAB promote the fermentation process of LAB to eventually lead to eradication of putrefactive- and pathogenic bacteria, and also increase the functionalities of kimchi. Accordingly, kimchi can be considered a vegetable probiotic food that contributes health benefits in a similar manner as yogurt as a dairy probiotic food. Further, the major ingredients of kimchi are cruciferous vegetables; and other healthy functional foods such as garlic, ginger, red pepper powder, and so on are added to kimchi as subingredients. As all of these ingredients undergo fermentation by LAB, kimchi is regarded as a source of LAB; and the fermentative byproducts from the functional ingredients significantly boost its functionality.

[1608] Han K et al. Contrasting effects of fresh and fermented kimchi consumption on gut microbiota composition2015;59(5):1004–1008. Mol Nutr Food Res. Link

Accumulating evidence suggests relationship of compositional changes of gut microbiota with onset of metabolic disorders and obesity. Kimchi, a traditional Korean side dish, is known for its beneficial impact on metabolic parameters and anti-obesity effects. The current study was designed to evaluate the association between gut microbiota and human genome after kimchi intervention in an effort to understand the molecular mechanism(s) underlying the antiobesity impact of kimchi. Twenty-four obese women were randomly assigned to either fresh or fermented kimchi group for eight weeks of kimchi intervention. Pyrosequencing of fecal microbiota and microarray analyses of blood samples revealed that fresh and fermented kimchi interventions exerted differential effects on the obesity-related clinical parameters. Correlations of these effects with changes in blood gene expression and gut microbial population were more evident in the fermented kimchi group than the fresh kimchi group.

[1609] Kim HY et al. Kimchi improves IBS symptoms — randomized clinical trial 2022;66. Food Nutr Res. 2022.

Randomized clinical trial examining the effect of kimchi on IBS symptoms (Food Nutr Res, 2022).

[1610] Choi IH et al. Kimchi, a fermented vegetable, improves serum lipid profiles in overweight subjects2013;16(3):223–229. J Med Food. Link

Vegetable-based diets have generally focused on their health benefits including negative associations with the serum cholesterol concentrations. The aim of this study was to investigate whether serum lipid concentrations are influenced by the amount of kimchi intake. For the study, 100 volunteers were assigned to 2 dietary groups, low (15 g/day, n=50) and high (210 g/day, n=50) kimchi intake, and were housed together in a dormitory for 7 days. Identical meals except with different amount of kimchi were provided and subjects were instructed to maintain their normal physical activity. Concentrations of fasting blood glucose (FBG), total glucose, total cholesterol and low density lipoprotein (LDL)-C significantly decreased in both groups after 7 days of kimchi intake, but the effects were dose dependent. Lipid lowering effects of kimchi were more profound in the subjects with total cholesterol and LDL-C level over 190 and 130 mg/dL, respectively, in both groups.

[1611] UNESCO. Kimjang, making and sharing kimchi in the Republic of Korea. 2013 Intangible Cultural Heritage list. . 2013. Link

UNESCO 2013 Intangible Cultural Heritage list entry on Kimjang, the making and sharing of kimchi in the Republic of Korea.

[1612] Patra JK et al. Kimchi and other widely consumed traditional fermented foods of Korea: a review2016;7:1493. Front Microbiol. Link

Different types of fermented foods such as chongkukjang, doenjang, ganjang, gochujang, and kimchi are plentifully available and widely consumed in north eastern Asian countries including Korea. Among them, kimchi is one of the most popular Korean traditional food. It is prepared by fermenting the baechu cabbage together with other vegetables and lactic acid bacteria (LAB) with functional potential. Many types of ingredients are added to kimchi to enhance its taste, flavor, nutritional value, texture etc. A number of bacteria are involved in the fermentation of kimchi, but LAB are the dominant species in the fermentation process. The addition of other sub ingredients and formation of different by-products during fermentation eventually leads to eradication of putrefactive and pathogenic bacteria, and also increase the functionalities, nutritional and nutraceutical potential of kimchi.

[1613] Monash University. Kimchi serving FODMAP data — green at 47 g. Link

Monash University FODMAP serving data for kimchi.

[1614] Allwood JG et al. Fermentation and the microbial ecology of miso2021;12:643343. Front Microbiol. Link

Miso is a well-known traditional Japanese fermented food, with a characteristic savory flavor and aroma, known predominately as the seasoning in miso soup. Miso production involves a two-stage fermentation, where first a mold, such as Aspergillus oryzae, is inoculated onto a substrate to make koji. A subsequent fermentation, this time by bacteria and yeast, occurs when the koji is added to a salt and soybean mash, with the miso left to ferment for up to 2 years. The microbial community of miso is considered essential to the development of the unique taste, texture, and nutritional profile of miso. Despite the importance of microorganisms in the production of miso, very little research has been undertaken to characterize and describe the microbial process. In this review, we provide an overview of the two-stage fermentation process, describe what is currently known about the microbial communities involved and consider any potential health benefits associated with the consumption of miso, along with food safety concerns.

[1615] Kondo H et al. Effect of miso soup consumption on nocturnal blood pressure2019. Hypertens Res. Link

The present study aimed to investigate the effects of the combination of Marukome Nenrin miso, which has natriuretic effects, and Marukome MK-34-1 miso, which has potent angiotensin converting enzyme inhibitory effects, on blood pressure (BP) in humans. A total of 40 subjects aged 40-69 years with high-normal BP or stage I hypertension were randomly assigned to two groups: 1) the miso group (32 g 2:1 w/w Nenrin and MK-34-1 with 3.8 g salt/day) or 2) the control soy food group (14.4 g soy food with 0.2 g salt/day). The levels of major nutrients were equal in the miso and control food servings, except for the fiber and Na levels, which were higher in the miso food serving. Daytime and nighttime BP were measured with an automated BP monitor. Compared with the soy food intake, miso intake for 8 weeks did not affect daytime clinical BP but significantly decreased nighttime BP without affecting pulse rate (PR). Moreover, miso shifted the nighttime BP profile to lower levels than those at baseline.

[1616] Yoshida M et al. Miso soup intake and pulse rate 2017. Tohoku J Exp Med. 2017.

Study in Tohoku J Exp Med (2017) on miso soup intake and pulse rate.

[1617] Messina M. Soy and health update: evaluation of the clinical and epidemiologic literature2016;8(12):754. Nutrients. Link

Soyfoods have long been recognized as sources of high-quality protein and healthful fat, but over the past 25 years these foods have been rigorously investigated for their role in chronic disease prevention and treatment. There is evidence, for example, that they reduce risk of coronary heart disease and breast and prostate cancer. In addition, soy alleviates hot flashes and may favorably affect renal function, alleviate depressive symptoms and improve skin health. Much of the focus on soyfoods is because they are uniquely-rich sources of isoflavones. Isoflavones are classified as both phytoestrogens and selective estrogen receptor modulators. Despite the many proposed benefits, the presence of isoflavones has led to concerns that soy may exert untoward effects in some individuals.

[1618] Setchell KDR et al. Bioavailability, disposition, and dose-response effects of soy isoflavones2003. J Clin Endocrinol Metab. Link

The pharmacokinetics of isoflavones in 10 healthy women were determined from serum appearance/disappearance concentration profiles and urinary excretions after single-bolus ingestion of 10, 20 or 40 g of soy nuts delivering increasing amounts of the conjugated forms of daidzein (6.6, 13.2 and 26.4 mg) and genistein (9.8, 19.6 and 39.2 mg). Peak serum daidzein and genistein concentrations were attained after 4-8 h, and elimination half-lives were 8.0 and 10.1 h, respectively. There were no differences in the pharmacokinetics of daidzein and genistein between pre- and postmenopausal women, indicating absorption and disposition of isoflavones to be independent of age or menopausal status. A curvilinear relationship was observed between the bioavailability of daidzein and genistein, apparent from the area under the curve to infinity (AUC(inf)) of the serum concentration-time profiles and the amount of isoflavones ingested. The mean fraction of the isoflavones excreted in urine decreased with increasing intake when expressed as a percentage of the administered dose (63.2 +/- 8.0, 54.4 +/- 8.1 and 44.0 +/- 4.3\%, respectively, for daidzein, and correspondingly, 25.2 +/- 5.3, 13.4 +/- 2.1 and 15.8 +/- 2.7\% for genistein), underscoring the trend toward nonlinear pharmacokinetics. Equol was identified as a metabolite in 30\% of women; it was present consistently in urine and blood from the same subjects.

[1619] Inoue Y et al. Miso intake and gut microbiota: a 14-day intervention 2021. Nutrients. 2021.

14-day intervention study on miso intake and the gut microbiota (Nutrients, 2021).

[1620] Watanabe H. Beneficial biological effects of miso with reference to radiation injury, cancer and hypertension2013;26(2):91–103. J Toxicol Pathol. Link

This review describes effects of miso with reference to prevention of radiation injury, cancer and hypertension with a twin focus on epidemiological and experimental evidence. Miso with a longer fermentation time increased crypt survival against radiation injury in mice. When evaluating different types of miso provided by different areas in Japan, miso fermented for a longer period increased the number of surviving crypts, and 180 days of fermentation was the most significant. Dietary administration of 180-day fermented miso inhibits the development of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and rat colon cancers in F344 rats. Miso was also effective in suppression of lung tumors, breast tumors in rats and liver tumors in mice. The incidence of gastric tumors of groups of rats given NaCl was higher than those of the groups given miso fermented for longer periods.

[1621] EFSA. Genistein and daidzein safety assessment2015. EFSA Journal. Link

EFSA safety assessment of the isoflavones genistein and daidzein, published in the EFSA Journal.

[1622] Schurgers LJ et al. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-72007;109(8):3279–3283. Blood. Link

Vitamin K is a cofactor in the production of blood coagulation factors (in the liver), osteocalcin (in bone), and matrix Gla protein (cartilage and vessel wall). Accumulating evidence suggests that for optimal bone and vascular health, relatively high intakes of vitamin K are required. The synthetic short-chain vitamin K(1) is commonly used in food supplements, but recently the natural long-chain menaquinone-7 (MK-7) has also become available as an over-the-counter (OTC) supplement. The purpose of this paper was to compare in healthy volunteers the absorption and efficacy of K(1) and MK-7. Serum vitamin K species were used as a marker for absorption and osteocalcin carboxylation as a marker for activity. Both K(1) and MK-7 were absorbed well, with peak serum concentrations at 4 hours after intake.

[1623] Sumi H et al. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto1987;43(10):1110–1111. Experientia. Link

A strong fibrinolytic activity was demonstrated in the vegetable cheese Natto, which is a typical soybean food eaten in Japan. The average activity was calculated at about 40 CU (plasmin units)/g wet weight. This novel fibrinolytic enzyme, named nattokinase, was easily extracted with saline. The mol. wt and pI were about 20,000 and 8.6, respectively. Nattokinase not only digested fibrin but also the plasmin substrate H-D-Val-Leu-Lys-pNA (S-2251), which was more sensitive to the enzyme than other substrates tried. Diisopropyl fluorophosphate and 2,2,2-trichloro-1-hydroxyethyl-o,o-dimethylphosphate strongly inhibited this fibrinolytic enzyme.

[1624] Kojima A et al. Natto intake and bone mineral density 2020. Eur J Clin Nutr. 2020.

Study in Eur J Clin Nutr (2020) on natto intake and bone mineral density.

[1625] Ikeda Y et al. Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese Population-Based Osteoporosis Study2006. J Nutr. Link

J Nutr Japanese population-based osteoporosis study on the association of fermented soybean (natto) intake with reduced bone loss in postmenopausal women.

[1626] Knapen MH et al. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women2013. Osteoporos Int. Link

UNLABELLED: We have investigated whether low-dose vitamin K2 supplements (menaquinone-7, MK-7) could beneficially affect bone health. Next to an improved vitamin K status, MK-7 supplementation significantly decreased the age-related decline in bone mineral density and bone strength. Low-dose MK-7 supplements may therefore help postmenopausal women prevent bone loss. INTRODUCTION: Despite contradictory data on vitamin K supplementation and bone health, the European Food Safety Authorities (EFSA) accepted the health claim on vitamin K's role in maintenance of normal bone. In line with EFSA's opinion, we showed that 3-year high-dose vitamin K1 (phylloquinone) and K2 (short-chain menaquinone-4) supplementation improved bone health after menopause. Because of the longer half-life and greater potency of the long-chain MK-7, we have extended these investigations by measuring the effect of low-dose MK-7 supplementation on bone health.

[1627] Chen H et al. Nattokinase: a promising alternative in prevention and treatment of cardiovascular diseases2018;13:1177271918785130. Biomark Insights. Link

Review in Biomark Insights (2018) on nattokinase as a promising alternative in the prevention and treatment of cardiovascular diseases.

[1628] Ozawa Y et al. γ-PGA + GOS clinical trial — increase. J-STAGE 2020. B. longum. 2020.

J-STAGE (2020) clinical trial on combined γ-PGA and GOS for increasing B. longum.

[1629] EFSA. Menaquinone (K₂) safety assessment2017. EFSA Journal. Link

EFSA safety assessment of menaquinone (vitamin K₂), published in the EFSA Journal.

[1630] Nout MJR, Kiers JL. Tempe fermentation, innovation and functionality: update into the third millennium2005;98(4):789–805. J Appl Microbiol. Link

Review in J Appl Microbiol (2005) on tempe fermentation, innovation and functionality.

[1631] Kiers JL et al. Effect of fermented soya beans on diarrhoea and feed efficiency in weaned piglets 2000;88(1):60–66. J Appl Microbiol. 2000.

Study in J Appl Microbiol (2000) on the effect of fermented soya beans on diarrhoea and feed efficiency in weaned piglets.

[1632] Reyes-Bastidas M et al. Biological, nutritional, and processing aspects of phytate 2010. Frontiers in Nutrition. 2010.

Article in Frontiers in Nutrition (2010) on the biological, nutritional, and processing aspects of phytate.

[1633] Afifah DN et al. Effect of tempeh on lipid profile: a randomized controlled trial 2020. Asia Pac J Clin Nutr. 2020.

Randomized controlled trial on the effect of tempeh on the lipid profile (Asia Pac J Clin Nutr, 2020).

[1634] Watanabe F. Vitamin B12 sources and bioavailability2007;232(10):1266–1274. (A tempeh növényi pszeudo-B12-t tartalmaz, amely humánban inaktív — kiegészítő B12-forrás szükséges vegán étrendben.)**. Exp Biol Med. Link

The usual dietary sources of vitamin B(12) are animal foods, meat, milk, egg, fish, and shellfish. As the intrinsic factor-mediated intestinal absorption system is estimated to be saturated at about 1.5-2.0 microg per meal under physiologic conditions, vitamin B(12) bioavailability significantly decreases with increasing intake of vitamin B(12) per meal. The bioavailability of vitamin B(12) in healthy humans from fish meat, sheep meat, and chicken meat averaged 42\%, 56\%-89\%, and 61\%-66\%, respectively. Vitamin B(12) in eggs seems to be poorly absorbed (< 9\%) relative to other animal food products. In the Dietary Reference Intakes in the United States and Japan, it is assumed that 50\% of dietary vitamin B(12) is absorbed by healthy adults with normal gastro-intestinal function. Some plant foods, dried green and purple lavers (nori) contain substantial amounts of vitamin B(12), although other edible algae contained none or only traces of vitamin B(12).

[1635] Hamilton-Reeves JM et al. Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis2010;94(3):997–1007. Fertil Steril. Link

Fertil Steril meta-analysis of clinical studies examining the effects of soy protein or isoflavones on reproductive hormones in men.

[1636] Messina M. Soybean isoflavone exposure does not have feminizing effects on men2010;93(7):2095–2104. Fertil Steril. 2095. Link

OBJECTIVE: To critically evaluate the clinical evidence, and when not available, the animal data, most relevant to concerns that isoflavone exposure in the form of supplements or soy foods has feminizing effects on men. DESIGN: Medline literature review and cross-reference of published data. RESULT(S): In contrast to the results of some rodent studies, findings from a recently published metaanalysis and subsequently published studies show that neither isoflavone supplements nor isoflavone-rich soy affect total or free testosterone (T) levels. Similarly, there is essentially no evidence from the nine identified clinical studies that isoflavone exposure affects circulating estrogen levels in men. Clinical evidence also indicates that isoflavones have no effect on sperm or semen parameters, although only three intervention studies were identified and none were longer than 3 months in duration. Finally, findings from animal studies suggesting that isoflavones increase the risk of erectile dysfunction are not applicable to men, because of differences in isoflavone metabolism between rodents and humans and the excessively high amount of isoflavones to which the animals were exposed.

[1637] Huang YC et al. Tempeh fermentation increases isoflavone aglycone content and bioavailability 2018;245:1140–1147. Food Chem. 2018.

Study in Food Chem (2018) on tempeh fermentation increasing isoflavone aglycone content and bioavailability.

[1638] Monash University. Tempeh — Low FODMAP serving guidelines. Monash FODMAP database. Link

Monash University FODMAP database low-FODMAP serving guidelines for tempeh.

[1639] Pérez-Díaz IM et al. Fermentation of cucumbers — review of the microbial ecologyUSDA-ARS. J Food Prot. Link

USDA-ARS review in J Food Prot on the microbial ecology of cucumber fermentation.

[1641] Nielsen ES et al. Lacto-fermented sauerkraut improves IBS symptoms2018;9(10):5323–5335. Food Funct. Link

[1642] McDonald LC et al. Acid tolerance of LAB1990. Appl Environ Microbiol. Link

[1643] Marco ML et al. Health benefits of fermented foods (ISAPP)2017;44:94–102. Curr Opin Biotechnol. 2017. Link

[1644] Miller KC et al. Reflex inhibition of electrically induced muscle cramps in hypohydrated humans (pickle juice)2010. Med Sci Sports Exerc. 2010. Link

INTRODUCTION: Anecdotal evidence suggests that ingesting small volumes of pickle juice relieves muscle cramps within 35 s of ingestion. No experimental evidence exists supporting the ingestion of pickle juice as a treatment for skeletal muscle cramps. METHODS: On two different days (1 wk apart), muscle cramps were induced in the flexor hallucis brevis (FHB) of hypohydrated male subjects (approximately 3\% body weight loss and plasma osmolality approximately 295 mOsm x kg(-1) H2O) via percutaneous tibial nerve stimulation. Thirty minutes later, a second FHB muscle cramp was induced and was followed immediately by the ingestion of 1 mL x kg(-1) body weight of deionized water or pickle juice (73.9 +/- 2.8 mL). RESULTS: Cramp duration and FHB EMG activity during the cramp were quantified, as well as the change in plasma constituents. Cramp duration (water = 151.9 +/- 12.9 s and pickle juice = 153.2 +/- 23.7 s) and FHB EMG activity (water = 60\% +/- 6\% and pickle juice = 68\% +/- 9\% of maximum voluntary isometric contraction EMG activity) were similar during the initial cramp induction without fluid ingestion (P > 0.05).

[1646] Monash University. Pickled cucumber FODMAP serving guide. Link

Monash University FODMAP serving guide for pickled cucumber.

[1649] Nielsen ES et al. Lacto-fermented sauerkraut improves IBS symptoms2018. Food Funct. Link

[1651] Behera SS et al. Lactic acid fermentation of vegetables: a review 2018. Crit Rev Food Sci Nutr. 2018.

Review in Crit Rev Food Sci Nutr (2018) on the lactic acid fermentation of vegetables.

[1652] Choi IH et al. Kimchi RCT — lipid profile2013. J Med Food. Link

[1653] CDC. Botulism prevention in home fermentation. 2023. . 2023. Link

CDC (2023) guidance on botulism prevention in home fermentation.

[1654] Monash University FODMAP. Fermented vegetables guide. Link

Monash University FODMAP guide for fermented vegetables.

[1655] Lavermicocca P et al. Table olive fermentation by strains. Int J Food Microbiol 2010. Lactobacillus plantarum. 2010.

Study in Int J Food Microbiol (2010) on table olive fermentation by Lactobacillus plantarum strains.

[1656] Accardi G et al. Nutraceutical effects of table green olives — pilot study 2016. Endocr Metab Immune Disord Drug Targets. 2016.

Pilot study on the nutraceutical effects of table green olives (Endocr Metab Immune Disord Drug Targets, 2016).

[1657] Pino A et al. LPG1 from table olives — probiotic in humans (RCT). J Funct Foods 2019. Lactobacillus pentosus. 2019.

Randomized controlled trial in J Funct Foods (2019) on the probiotic effect in humans of Lactobacillus pentosus LPG1 from table olives.

[1658] Rocha J et al. Arbequina olives in spontaneously hypertensive rats — BP and gut microbiota 2020. RSC Adv. 2020.

Study in RSC Adv (2020) on the effect of Arbequina olives on blood pressure and gut microbiota in spontaneously hypertensive rats.

[1659] EFSA. Olive oil polyphenols health claim (Regulation 432/2012/EU). . 2012. Link

EFSA health claim on olive oil polyphenols (Regulation 432/2012/EU).

[1660] Bautista-Gallego J et al. Brining for table olives — review 2013. Food Microbiol. 2013.

Review in Food Microbiol (2013) on brining for table olives.

[1661] Hurtado A et al. Lactic acid bacteria from fermented table olives 2012. Food Microbiol. 2012.

Study in Food Microbiol (2012) on lactic acid bacteria from fermented table olives.

[1662] Monash University. Olives FODMAP serving guide. Link

Monash University FODMAP serving guide for olives.

[1663] Johnston CS et al. Vinegar improves insulin sensitivity to a high-carbohydrate meal in subjects with insulin resistance or type 2 diabetes. Diabetes Care 2004;27(1):281–282. . 2004. Link

Small human crossover study (Johnston et al., Diabetes Care 2004) assessing the effect of vinegar on the postprandial glucose and insulin responses to a high-carbohydrate meal in insulin-resistant or type 2 diabetic subjects and in insulin-sensitive controls. Vinegar taken before the meal improved insulin sensitivity and attenuated postprandial glycaemia and insulinaemia, with a more pronounced effect in the insulin-resistant subjects.

[1664] Mitrou P et al. Vinegar consumption increases insulin-stimulated glucose uptake by the forearm muscle in humans with type 2 diabetes. J Diabetes Res 2015;2015:175204. . 2015. Link

BACKGROUND AND AIMS: Vinegar has been shown to have a glucose-lowering effect in patients with glucose abnormalities. However, the mechanisms of this effect are still obscure. The aim of this randomised, crossover study was to investigate the effect of vinegar on glucose metabolism in muscle which is the most important tissue for insulin-stimulated glucose disposal. MATERIALS AND METHODS: Eleven subjects with DM2 consumed vinegar or placebo (at random order on two separate days, a week apart), before a mixed meal. Plasma glucose, insulin, triglycerides, nonesterified fatty acids (NEFA), and glycerol were measured preprandially and at 30-60 min for 300 min postprandially from the radial artery and from a forearm vein. Muscle blood flow was measured with strain-gauge plethysmography.

[1665] Kondo T et al. Vinegar intake reduces body weight, body fat mass, and serum triglyceride levels in obese Japanese subjects. Biosci Biotechnol Biochem 2009;73(8):1837–1843. . 2009. Link

Acetic acid (AcOH), a main component of vinegar, recently was found to suppress body fat accumulation in animal studies. Hence we investigated the effects of vinegar intake on the reduction of body fat mass in obese Japanese in a double-blind trial. The subjects were randomly assigned to three groups of similar body weight, body mass index (BMI), and waist circumference. During the 12-week treatment period, the subjects in each group ingested 500 ml daily of a beverage containing either 15 ml of vinegar (750 mg AcOH), 30 ml of vinegar (1,500 mg AcOH), or 0 ml of vinegar (0 mg AcOH, placebo). Body weight, BMI, visceral fat area, waist circumference, and serum triglyceride levels were significantly lower in both vinegar intake groups than in the placebo group. In conclusion, daily intake of vinegar might be useful in the prevention of metabolic syndrome by reducing obesity.

[1666] Khezri SS et al. Beneficial effects of apple cider vinegar on weight management, visceral adiposity index and lipid profile in overweight or obese subjects receiving restricted calorie diet: a randomized clinical trial. J Funct Foods 2018;43:95–102. . 2018. Link

12-week randomized clinical trial by Khezri et al. (J Funct Foods 2018) in which overweight or obese subjects (n=39) on a restricted-calorie diet (250 kcal/day deficit) received either apple cider vinegar (30 mL/day) or no vinegar. The vinegar group showed significant reductions in body weight, BMI, hip circumference, visceral adiposity index (VAI) and appetite score, as well as reduced plasma triglycerides and increased HDL-cholesterol compared with the control group.

[1667] Lhotta K et al. Hypokalemia, hyperreninemia and osteoporosis in a patient ingesting large amounts of cider vinegar. Nephron 1998;80(2):242–243. . 1998. Link

Case report in Nephron (1998) of hypokalemia, hyperreninemia and osteoporosis in a patient ingesting large amounts of cider vinegar.

[1668] Petsiou EI et al. Effect and mechanisms of action of vinegar on glucose metabolism, lipid profile, and body weight. Nutr Rev 2014;72(10):651–661. . 2014. Link

The aim of this review is to summarize the effects of vinegar on glucose and lipid metabolism. Several studies have demonstrated that vinegar can help reduce hyperglycemia, hyperinsulinemia, hyperlipidemia, and obesity. Other studies, however, have shown no beneficial effect on metabolism. Several mechanisms have been proposed to explain these metabolic effects, including delayed gastric emptying and enteral absorption, suppression of hepatic glucose production, increased glucose utilization, upregulation of flow-mediated vasodilation, facilitation of insulin secretion, reduction in lipogenesis, increase in lipolysis, stimulation of fecal bile acid excretion, increased satiety, and enhanced energy expenditure. Although some evidence supports the use of vinegar as a complementary treatment in patients with glucose and lipid abnormalities, further large-scale long-term trials with impeccable methodology are warranted before definitive health claims can be made.

[1669] Hill LL et al. Esophageal injury by apple cider vinegar tablets and subsequent evaluation of products. J Am Diet Assoc 2005;105(7):1141–1144. . 2005. Link

Apple cider vinegar products are advertised in the popular press and over the Internet for treatment of a variety of conditions. After an adverse event was reported to the authors, eight apple cider vinegar tablet products were tested for pH, component acid content, and microbial growth. Considerable variability was found between the brands in tablet size, pH, component acid content, and label claims. Doubt remains as to whether apple cider vinegar was in fact an ingredient in the evaluated products. The inconsistency and inaccuracy in labeling, recommended dosages, and unsubstantiated health claims make it easy to question the quality of the products.

[1670] Liljeberg H, Björck I. Delayed gastric emptying rate may explain improved glycaemia in healthy subjects to a starchy meal with added vinegar. Eur J Clin Nutr 1998;52(5):368–371. . 1998. Link

OBJECTIVES: The aim of the study was to evaluate the possible influence of acetic acid (administered as vinegar) on the postprandial glucose and insulin responses, and the potential involvement of a modified gastric emptying rate was studied by use of paracetamol as a marker. DESIGN: The white bread reference meal as well as the corresponding meal supplemented with vinegar had the same content of starch, protein and fat. The meals were served in the morning after an over-night fast and in random order. Capillary blood samples for analysis of glucose, insulin and paracetamol were collected postprandially. SETTING: The study was performed at the Department of Applied Nutrition and Food Chemistry, Lund University, Sweden. SUBJECTS: Ten healthy volunteers, seven women and three men, aged 22-51 y, with normal body mass indices were recruited.

[1671] Ho CW et al. Varieties, production, composition and health benefits of vinegars: a review. Food Chem 2017;221:1621–1630. . 2017. Link

Vinegars are liquid products produced from the alcoholic and subsequent acetous fermentation of carbohydrate sources. They have been used as remedies in many cultures and have been reported to provide beneficial health effects when consumed regularly. Such benefits are due to various types of polyphenols, micronutrients and other bioactive compounds found in vinegars that contribute to their pharmacological effects, among them, antimicrobial, antidiabetic, antioxidative, antiobesity and antihypertensive effects. There are many types of vinegars worldwide, including black vinegar, rice vinegar, balsamic vinegar and white wine vinegar. All these vinegars are produced using different raw materials, yeast strains and fermentation procedures, thus giving them their own unique tastes and flavours. The main volatile compound in vinegar is acetic acid, which gives vinegar its strong, sour aroma and flavour.

[1672] Liu Q, Tang GY, Zhao CN, Gan RY, Li HB. Antioxidant activities, phenolic profiles, and organic acid contents of fruit vinegars2019;8(4):78. Antioxidants. Link

Fruit vinegars are popular condiments worldwide. Antioxidants and organic acids are two important components of the flavors and health benefits of fruit vinegars. This study aimed to test the antioxidant activities, phenolic profiles, and organic acid contents of 23 fruit vinegars. The results found that the 23 fruit vinegars varied in ferric-reducing antioxidant power (FRAP, 0.15⁻23.52 μmol Fe(II)/mL), Trolox equivalent antioxidant capacity (TEAC, 0.03⁻7.30 μmol Trolox/mL), total phenolic content (TPC, 29.64⁻3216.60 mg gallic acid equivalent/L), and total flavonoid content (TFC, 2.22⁻753.19 mg quercetin equivalent/L) values. Among the 23 fruit vinegars, the highest antioxidant activities were found in balsamic vinegar from Modena (Galletti), Aceto Balsamico di Modena (Monari Federzoni), red wine vinegar (Kühne), and red wine vinegar (Galletti). In addition, polyphenols and organic acids might be responsible for the antioxidant activities of fruit vinegars.

[1673] Sakakibara S et al. Vinegar intake enhances flow-mediated vasodilatation2010;74(5):1055–1061. Biosci Biotechnol Biochem. Link

This study examined the effect of acetate on endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVECs) by immunoblotting assay and the ability of acetic acid to upregulate flow-mediated vasodilatation in humans. In HUVECs, acetate induced a biphasic increase in the phosphorylated form of eNOS. The amount of phosphorylated eNOS was significantly increased by exposure to 200 mumol/l acetate for 20 min (early phase) and for 4 h (late phase). The inhibitors of cAMP-dependent protein kinase (PKA) and AMP-activated protein kinase (AMPK) blocked acetate-induced eNOS phosphorylation in the early and the late phase respectively. Furthermore, in postmenopausal women, maximum forearm blood flow (FBF) in response to shear stress increased in the vinegar (acetic acid) administered group compared to the placebo group. These results suggest that acetic acid-induced eNOS phosphorylation contributes to upregulation of flow-mediated vasodilatation in humans.

[1674] Shishehbor F, Mansoori A, Shirani F. Vinegar consumption can attenuate postprandial glucose and insulin responses; a systematic review and meta-analysis of clinical trials2017;127:1–9. Diabetes Res Clin Pract. Link

OBJECTIVE: Postprandial hyperglycemia plays a decisive role in the development of chronic metabolic disorders. The effect of vinegar intake with a meal on postprandial glucose has been studied in several trials with conflicting results. RESEARCH METHODS AND PROCEDURES: The purpose of the current study was to systematically review control trials that report on the effect of vinegar intake on postprandial glucose response. Postprandial insulin response was considered as secondary outcome. RESULTS: The pooled analysis of studies revealed a significant mean glucose and insulin area under the curve (AUC) reduction in participants who consumed vinegar compared with the control group (standard mean difference=-0.60, 95\%CI -1.08 to -0.11, p=0.01 and -1.30, 95\%CI -1.98 to -0.62, p<0.001, respectively). CONCLUSIONS: The findings suggest that vinegar can be effective in reducing postprandial glucose and insulin levels, indicating it could be considered as an adjunctive tool for improving glycemic control.

[1675] Shishehbor F et al. Apple cider vinegar attenuates lipid profile in normal and diabetic rats (an animal study)2008;11(23):2634–2638. Pak J Biol Sci. 2008. Link

Animal study (Pak J Biol Sci) on apple cider vinegar's effect on the lipid profile in normal and diabetic rats.

[1676] Marco ML et al. Health benefits of fermented foods: microbiota and beyond2017;44:94–102. Curr Opin Biotechnol. Link

[1677] Petsiou EI et al. Effect and mechanisms of action of vinegar on glucose metabolism, lipid profile, and body weight2014;72(10):651–661. Nutr Rev. Link

[1678] Ho CW et al. Varieties, production, composition and health benefits of vinegars: a review2017;221:1621–1630. Food Chem. Link

[1679] Johnston CS et al. Vinegar improves insulin sensitivity to a high-carbohydrate meal in subjects with insulin resistance or type 2 diabetes2004;27(1):281–282. Diabetes Care. Link

[1680] Tagliazucchi D et al. Antioxidant properties of traditional balsamic vinegar and influence of in vitro digestion2007;103(4):1419–1426. Food Chem. Link

Tagliazucchi et al. (Food Chem 2007) investigated the antioxidant properties of traditional balsamic vinegar and the influence of in vitro digestion. The work indicates that the antioxidant activity of aged traditional balsamic vinegar is due both to high-molecular-weight melanoidins and to low-molecular-weight compounds (polyphenols, phenolic acids, catechins, flavonols, tannins, and Maillard/caramelization products).

[1681] Sugiyama M et al. Glycemic index of single and mixed meal foods among common Japanese foods with white rice as a reference food2003;57(6):743–752. Eur J Clin Nutr. Link

OBJECTIVE: The objectives were to examine the feasibility of using white rice as a reference food in the study of glycemic index (GI) and to examine the GI values of both single and mixed meal foods among rice species, processed rice products, beans, and dairy products. DESIGN: Subjects were served with 50 g carbohydrate content of white rice at least two times (maximum three times) and test food once after separate overnight fasts. Capillary blood glucose measurements were carried out before and during 120 min after each food load. SETTING: The study was carried out in an outpatient setting. SUBJECTS: A total of 58 (38 females and 20 males) nondiseased subjects, mean aged 37 y and mean BMI 22 kg/m(2) were included. RESULT: The correlation between incremental area under curve of white rice and glucose was r=0.853 (n=10, P <0.0001) and white rice was considered suitable to be used as a reference food.

[1687] Nishidai S et al. Kurosu, a traditional vinegar produced from unpolished rice, suppresses lipid peroxidation in vitro and in mouse skin2000;64(9):1909–1914. Biosci Biotechnol Biochem. 1909. Link

The in vitro antioxidative activities of various kinds of vinegar were investigated by using a linoleic acid autoxidation model detected by the thiobarbituric acid (TBA) method and the 1,1-diphenyl-2-picrylhydrazyl radical system. An ethyl acetate extract of Kurosu (EK), a vinegar made from unpolished rice, exhibited the highest antioxidative activity in both systems. EK (5 mg) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema formation (14\%) and myeloperoxidase activity (52\%, P< 0.01) in female ICR mouse skin. Furthermore, EK significantly suppressed double TPA application-induced H2O2 generation (53\%, P< 0.01) and lipid peroxidation determined by the TBA-reacting substance level (95 \%, P< 0.01). In a two-stage carcinogenesis experiment with dimethylbenz[a]anthracene/TPA, EK significantly reduced the number of tumors per mouse by 36\% (P<0.05) at 15 weeks after promotion. These results suggest that the antitumor-promoting effect may be partially due to the antioxidative properties of EK such as the decomposition of free radicals and interference with free radical-generating leukocytes.

[1688] Tamang JP et al. Functional properties of microorganisms in fermented foods2016;7:578. Front Microbiol. Link

Fermented foods have unique functional properties imparting some health benefits to consumers due to presence of functional microorganisms, which possess probiotics properties, antimicrobial, antioxidant, peptide production, etc. Health benefits of some global fermented foods are synthesis of nutrients, prevention of cardiovascular disease, prevention of cancer, gastrointestinal disorders, allergic reactions, diabetes, among others. The present paper is aimed to review the information on some functional properties of the microorganisms associated with fermented foods and beverages, and their health-promoting benefits to consumers.

[1689] Setchell KDR, Brown NM, Desai P, et al. Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements2001;131(4 Suppl):1362S–1375S. J Nutr. Link

The pharmacokinetic behavior of naturally occurring isoflavones has been determined for the first time in healthy adults. We compared plasma kinetics of pure daidzein, genistein and their beta-glycosides administered as a single-bolus dose to 19 healthy women. This study demonstrates differences in the pharmacokinetics of isoflavone glycosides compared with their respective beta-glycosides. Although all isoflavones are efficiently absorbed from the intestinal tract, there are striking differences in the fate of aglycones and beta-glycosides. Mean time to attain peak plasma concentrations (t(max)) for the aglycones genistein and daidzein was 5.2 and 6.6 h, respectively, whereas for the corresponding beta-glycosides, the t(max) was delayed to 9.3 and 9.0 h, respectively, consistent with the residence time needed for hydrolytic cleavage of the glycoside moiety for bioavailability. The apparent volume of distribution of isoflavones confirms extensive tissue distribution after absorption.

[1690] Messina M. Soy and breast cancer: a comprehensive review 2014;10(3):265–292. Womens Health. 2014.

Comprehensive review in Womens Health (2014) on soy and breast cancer.

[1691] Chen M, Rao Y, Zheng Y, et al. Association between soy isoflavone intake and breast cancer risk for pre- and post-menopausal women: a meta-analysis of epidemiological studies2014;9(2):e89288. PLoS One. Link

BACKGROUND: Conclusions drawn from meta-analyses on the association between soy isoflavone intake and breast cancer risk for pre- and post-menopausal women are not fully consistent. These meta-analyses did not explore the influence of different study designs on the pooled results on the basis of distinguishing between pre- and post-menopausal women. METHODOLOGY AND PRINCIPAL FINDINGS: We performed a meta-analysis of 35 studies which reported results of association between soy isoflavone intake and breast cancer risk for pre- and/or post-menopausal women, calculated pooled odds ratios and their 95\% confidence intervals of pre- and post-menopausal women respectively, and further explored soy isoflavone-breast cancer association on the basis of considering different study regions and designs. Summary results suggested that soy isoflavone intake has a protective effect against breast cancer for both pre- and post-menopausal women. However, they are influenced by study design and region. Pooled ORs of studies carried out in Asian countries suggested that soy isoflavone's protective effect exist in both pre- and post-menopausal women (OR = 0.59, 95\%CI: 0.48-0.69 for premenopausal women; OR = 0.59, 95\%CI: 0.44-0.74 for postmenopausal women).

[1693] Sanlier N et al. Health benefits of fermented foods2019;59(3):506–527. Crit Rev Food Sci Nutr. Link

In the past, the beneficial effects of fermented foods on health were unknown, and so people primarily used fermentation to preserve foods, enhance shelf life, and improve flavour. Fermented foods became an important part of the diet in many cultures, and over time fermentation has been associated with many health benefits. Because of this, the fermentation process and the resulting fermented products have recently attracted scientific interest. In addition, microorganisms contributing to the fermentation process have recently been associated with many health benefits, and so these microorganisms have become another focus of attention. Lactic acid bacteria (LAB) have been some of the most studied microorganisms. During fermentation, these bacteria synthesize vitamins and minerals, produce biologically active peptides with enzymes such as proteinase and peptidase, and remove some non-nutrients.

[1694] Soni SK, Sandhu DK. Indian fermented foods: microbiological and biochemical aspects 1989;29:355–366. Indian J Microbiol. 1989.

Article in Indian J Microbiol (1989) on the microbiological and biochemical aspects of Indian fermented foods.

[1697] Steinkraus KH. Industrialization of indigenous fermented foods. Marcel Dekker, 2004. . 2004. Link

Steinkraus's book (Marcel Dekker, 2004) on the industrialization of indigenous fermented foods.

[1698] Reddy NR et al. Phytates in legumes and cereals1982;28:1–92. Adv Food Res. Link

Review in Adv Food Res (1982) on phytates in legumes and cereals.

[1699] Battcock M, Azam-Ali S. Fermented fruits and vegetables — global perspective. FAO Agric Serv Bull 134, 1998. . 1998. Link

FAO Agric Serv Bull 134 (1998) global perspective on fermented fruits and vegetables.

[1700] Madhu AN, Giribhattanavar P, Narayan MS, Prapulla SG. Probiotic lactic acid bacterium from kanjika as a potential source of vitamin B12: evidence from LC-MS, immunological and microbiological techniques2010;32(4):503–506. Biotechnol Lett. Link

Study (Biotechnol Lett) evaluating a probiotic lactic acid bacterium from kanjika as a potential vitamin B12 source using LC-MS, immunological and microbiological techniques.

[1701] Ashenafi M. A review on the microbiology of indigenous fermented foods and beverages of Ethiopia 2006;5(2):189–245. Ethiop J Biol Sci. 2006.

Review in Ethiop J Biol Sci (2006) on the microbiology of indigenous fermented foods and beverages of Ethiopia.

[1702] Dereje B, Girma A, Mamo D, Chalchisa T. Glycemic index of Ethiopian foods commonly consumed in Africa2019;2019:8564879. J Diabetes Res. 2019. Link

BACKGROUND: Determining the glycemic index and load of foods has significant impact on meal planning for diabetes. However, there is no data on the glycemic index (GI) and glycemic load (GL) of Ethiopian foods. Therefore, the aim of this study was to analyze the glycemic index and glycemic load of Teff Injera, Corn Injera, and White Wheat Bread. METHODS: Experimental study design was conducted among selected healthy adults. Teff Injera, Corn Injera, and White Wheat Bread were selected as test foods for the study, and glucose was used as the reference food. The postprandial glucose concentrations in the blood were recorded at 0, 15, 30, 45, 90, and 120 minutes.

[1705] Saturni L et al. The gluten-free diet: safety and nutritional quality2010;2(1):16–34. Nutrients. Link

The prevalence of celiac disease (CD), an autoimmune enteropathy, characterized by chronic inflammation of the intestinal mucosa, atrophy of intestinal villi and several clinical manifestations has increased in recent years. Subjects affected by CD cannot tolerate gluten protein, a mixture of storage proteins contained in several cereals (wheat, rye, barley and derivatives). Gluten free-diet remains the cornerstone treatment for celiac patients. Therefore the absence of gluten in natural and processed foods represents a key aspect of food safety of the gluten-free diet. A promising area is the use of minor or pseudo-cereals such as amaranth, buckwheat, quinoa, sorghum and teff. The paper is focused on the new definition of gluten-free products in food label, the nutritional properties of the gluten-free cereals and their use to prevent nutritional deficiencies of celiac subjects.

[1706] Baye K et al. Phytate, zinc, iron and calcium content of selected raw and prepared foods consumed in rural Ethiopia2014;33(2):163–172. J Food Compos Anal. Link

Baye et al. (J Food Compos Anal 2014) analysed the phytate, zinc, iron and calcium content of selected raw and prepared foods consumed in rural Sidama, Southern Ethiopia, with implications for bioavailability. Non-fermented cereal foods showed high phytate:zinc molar ratios (>15-20), indicating low zinc bioavailability, whereas fermentation markedly reduced phytate content and improved mineral availability; tef-based foods were good sources of iron and calcium.

[1708] Wu AH, Yu MC, Tseng CC, Pike MC. Epidemiology of soy exposures and breast cancer risk2008;98(1):9–14. Br J Cancer. Link

Most of the early studies published on soy and breast cancer were not designed to test the effect of soy; the assessment of soy intake was usually crude and few potential confounders were considered in the analysis. In this review, we focused on studies with relatively complete assessment of dietary soy exposure in the targeted populations and appropriate consideration for potential confounders in the statistical analysis of study data. Meta-analysis of the 8 (1 cohort, 7 case-control) studies conducted in high-soy-consuming Asians show a significant trend of decreasing risk with increasing soy food intake. Compared to the lowest level of soy food intake (or=20 mg isoflavones per day). In contrast, soy intake was unrelated to breast cancer risk in studies conducted in the 11 low-soy-consuming Western populations whose average highest and lowest soy isoflavone intake levels were around 0.8 and 0.15 mg per day, respectively. Thus, the evidence to date, based largely on case-control studies, suggest that soy food intake in the amount consumed in Asian populations may have protective effects against breast cancer.

[1712] Whiting S et al. Capsaicinoids and capsinoids on weight management: a meta-analysis2014;73:183–188. Appetite. Link

OBJECTIVE: Capsaicinoids are a group of chemicals naturally occurring in chilli peppers with bioactive properties that may help to support weight management. The aim of the present study was to conduct a meta-analysis investigating the potential effects of capsaicinoids on energy intake, to clarify previous observations and form evidence-based conclusions about possible weight management roles. METHODS: Medical databases (Medline, Web of Knowledge and Scopus) were systematically searched for papers. Search terms were: 'capsaicin(*)' or 'red pepper' or 'chilli(*)' or 'chili(*)' with 'satiety' or 'energy intake'. Of the seventy-four clinical trials identified, 10 were included, 8 of which provided results suitable to be combined in analysis (191 participants). From the studies, 19 effect sizes were extracted and analysed using MIX meta-analysis software.

[1715] EFSA NDA Panel. Scientific opinion on the substantiation of health claims related to live yoghurt cultures and improved lactose digestion2010;8(10):1763. EFSA Journal. Link

EFSA NDA Panel opinion under Article 13(1) (claims ID 1143, 2976): based on the submitted human studies the Panel established a cause-and-effect relationship between consumption of live yoghurt cultures (L. delbrueckii subsp. bulgaricus and S. thermophilus) and improved digestion of lactose in yoghurt among lactose maldigesters. To obtain the effect the yoghurt should contain at least 10^8 CFU live starter bacteria per gram.

[1716] Codex Alimentarius. Standard for Fermented Milks (CXS 243-2003, Rev. 2025). . 2003. Link

Codex Alimentarius Standard for Fermented Milks (CXS 243-2003, Rev. 2025).

[1718] Marteau P et al. Bifidobacterium animalis strain DN-173 010 shortens colonic transit time2002. Aliment Pharmacol Ther. Link

BACKGROUND: A previous study has suggested that Bifidobacterium animalis DN-173 010 shortens the colonic transit time in women. AIM: To confirm this effect and to determine whether modifications of the faecal bacterial mass and/or faecal secondary bile salts may be the explanation. METHODS: A double-blind, cross-over study was performed. Thirty-six healthy women were studied in four consecutive 10-day periods. During periods 2 and 4, they ingested three 125 g cups per day of a fermented milk which was either a product containing B. animalis DN-173 010 or a control without bifidobacteria. Periods 1 and 3 were run-in and washout periods, respectively.

[1719] Hill C et al. ISAPP consensus on the term "probiotic"2014;11(8):506–514. Nat Rev Gastroenterol Hepatol. 2014. Link

[1720] Sanders ME et al. Probiotics and prebiotics in intestinal health and disease2019;16(10):605–616. Nat Rev Gastroenterol Hepatol. Link

Probiotics and prebiotics are microbiota-management tools for improving host health. They target gastrointestinal effects via the gut, although direct application to other sites such as the oral cavity, vaginal tract and skin is being explored. Here, we describe gut-derived effects in humans. In the past decade, research on the gut microbiome has rapidly accumulated and has been accompanied by increased interest in probiotics and prebiotics as a means to modulate the gut microbiota. Given the importance of these approaches for public health, it is timely to reiterate factual and supporting information on their clinical application and use. In this Review, we discuss scientific evidence on probiotics and prebiotics, including mechanistic insights into health effects.

[1721] Mantzouridou FT, Paraskevopoulou A. Yogurt manufacture — chemistry & technology 2020. Crit Rev Food Sci Nutr. 2020.

Article in Crit Rev Food Sci Nutr (2020) on yogurt manufacture chemistry and technology.

[1722] . Metchnikoff E1908. The Prolongation of Life: Optimistic Studies. Link

Metchnikoff's 1908 work, The Prolongation of Life: Optimistic Studies.

[1723] Marsh AJ et al. Sequencing-based analysis of the microbial composition of water kefir from multiple sources2013. FEMS Microbiol Lett. Link

Water kefir is a water-sucrose-based beverage, fermented by a symbiosis of bacteria and yeast to produce a final product that is lightly carbonated, acidic and that has a low alcohol percentage. The microorganisms present in water kefir are introduced via water kefir grains, which consist of a polysaccharide matrix in which the microorganisms are embedded. We aimed to provide a comprehensive sequencing-based analysis of the bacterial population of water kefir beverages and grains, while providing an initial insight into the corresponding fungal population. To facilitate this objective, four water kefirs were sourced from the UK, Canada and the United States. Culture-independent, high-throughput, sequencing-based analyses revealed that the bacterial fraction of each water kefir and grain was dominated by Zymomonas, an ethanol-producing bacterium, which has not previously been detected at such a scale. The other genera detected were representatives of the lactic acid bacteria and acetic acid bacteria.

[1726] Bellikci-Koyu E et al. Effects of regular kefir consumption on gut microbiota in metabolic syndrome — RCT2019. Nutrients. Link

Several health-promoting effects of kefir have been suggested, however, there is limited evidence for its potential effect on gut microbiota in metabolic syndrome This study aimed to investigate the effects of regular kefir consumption on gut microbiota composition, and their relation with the components of metabolic syndrome. In a parallel-group, randomized, controlled clinical trial setting, patients with metabolic syndrome were randomized to receive 180 mL/day kefir (n = 12) or unfermented milk (n = 10) for 12 weeks. Anthropometrical measurements, blood samples, blood pressure measurements, and fecal samples were taken at the beginning and end of the study. Fasting insulin, HOMA-IR, TNF-α, IFN-γ, and systolic and diastolic blood pressure showed a significant decrease by the intervention of kefir (p ≤ 0.05, for each). However, no significant difference was obtained between the kefir and unfermented milk groups (p > 0.05 for each). Gut microbiota analysis showed that regular kefir consumption resulted in a significant increase only in the relative abundance of Actinobacteria (p = 0.023).

[1727] Yang J et al. 3,500-year-old kefir cheese from Xinjiang2024. Cell. Link

Despite the long history of consumption of fermented dairy, little is known about how the fermented microbes were utilized and evolved over human history. Here, by retrieving ancient DNA of Bronze Age kefir cheese (∼3,500 years ago) from the Xiaohe cemetery, we explored past human-microbial interactions. Although it was previously suggested that kefir was spread from the Northern Caucasus to Europe and other regions, we found an additional spreading route of kefir from Xinjiang to inland East Asia. Over evolutionary history, the East Asian strains gained multiple gene clusters with defensive roles against environmental stressors, which can be a result of the adaptation of Lactobacillus strains to various environmental niches and human selection. Overall, our results highlight the role of past human activities in shaping the evolution of human-related microbes, and such insights can, in turn, provide a better understanding of past human behaviors.

[1728] Rosa DD et al. Milk kefir: nutritional, microbiological and health benefits2017. Nutr Res Rev. Link

Kefir is fermented milk produced from grains that comprise a specific and complex mixture of bacteria and yeasts that live in a symbiotic association. The nutritional composition of kefir varies according to the milk composition, the microbiological composition of the grains used, the time/temperature of fermentation and storage conditions. Kefir originates from the Caucasus and Tibet. Recently, kefir has raised interest in the scientific community due to its numerous beneficial effects on health. Currently, several scientific studies have supported the health benefits of kefir, as reported historically as a probiotic drink with great potential in health promotion, as well as being a safe and inexpensive food, easily produced at home. Regular consumption of kefir has been associated with improved digestion and tolerance to lactose, antibacterial effect, hypocholesterolaemic effect, control of plasma glucose, anti-hypertensive effect, anti-inflammatory effect, antioxidant activity, anti-carcinogenic activity, anti-allergenic activity and healing effects.

[1729] Pogačić T et al. Microbiota of kefir grains2013. Mljekarstvo. Link

Study of the microbiota of kefir grains, characterising the bacterial and yeast communities responsible for fermentation.

[1730] ISAPP. Fermented foods consensus 2021. Nat Rev Gastroenterol Hepatol. 2021. Link

An expert panel was convened in September 2019 by The International Scientific Association for Probiotics and Prebiotics (ISAPP) to develop a definition for fermented foods and to describe their role in the human diet. Although these foods have been consumed for thousands of years, they are receiving increased attention among biologists, nutritionists, technologists, clinicians and consumers. Despite this interest, inconsistencies related to the use of the term 'fermented' led the panel to define fermented foods and beverages as "foods made through desired microbial growth and enzymatic conversions of food components". This definition, encompassing the many varieties of fermented foods, is intended to clarify what is (and is not) a fermented food. The distinction between fermented foods and probiotics is further clarified. The panel also addressed the current state of knowledge on the safety, risks and health benefits, including an assessment of the nutritional attributes and a mechanistic rationale for how fermented foods could improve gastrointestinal and general health.

[1731] Salque M et al. Earliest evidence for cheese making in the sixth millennium BC in northern Europe2013;493(7433):522–525. Nature. Link

The introduction of dairying was a critical step in early agriculture, with milk products being rapidly adopted as a major component of the diets of prehistoric farmers and pottery-using late hunter-gatherers. The processing of milk, particularly the production of cheese, would have been a critical development because it not only allowed the preservation of milk products in a non-perishable and transportable form, but also it made milk a more digestible commodity for early prehistoric farmers. The finding of abundant milk residues in pottery vessels from seventh millennium sites from north-western Anatolia provided the earliest evidence of milk processing, although the exact practice could not be explicitly defined. Notably, the discovery of potsherds pierced with small holes appear at early Neolithic sites in temperate Europe in the sixth millennium BC and have been interpreted typologically as 'cheese-strainers', although a direct association with milk processing has not yet been demonstrated. Organic residues preserved in pottery vessels have provided direct evidence for early milk use in the Neolithic period in the Near East and south-eastern Europe, north Africa, Denmark and the British Isles, based on the δ(13)C and Δ(13)C values of the major fatty acids in milk. Here we apply the same approach to investigate the function of sieves/strainer vessels, providing direct chemical evidence for their use in milk processing.

[1732] Stadhouders J. Cheese as carrier for probiotic bacteria 1999. Int Dairy J. 1999.

Paper examining cheese as a carrier matrix for probiotic bacteria.

[1733] Sharp MD et al. Probiotic Gouda enhances immune function in elderly 2008. J Dairy Sci. 2008.

Study on the effect of a probiotic-enriched Gouda cheese on immune function in elderly subjects.

[1734] Cousin FJ et al. Probiotic. Microorganisms 2017. Propionibacterium freudenreichii. 2017. Link

Dairy propionibacteria are used as cheese ripening starters, as biopreservative and as beneficial additives, in the food industry. The main species, Propionibacterium freudenreichii, is known as GRAS (Generally Recognized As Safe, USA, FDA). In addition to another dairy species, Propionibacterium acidipropionici, they are included in QPS (Qualified Presumption of Safety) list. Additional to their well-known technological application, dairy propionibacteria increasingly attract attention for their promising probiotic properties. The purpose of this review is to summarize the probiotic characteristics of dairy propionibacteria reported by the updated literature. Indeed, they meet the selection criteria for probiotic bacteria, such as the ability to endure digestive stressing conditions and to adhere to intestinal epithelial cells.

[1735] EFSA. Tyramine and biogenic amines safety2011. EFSA Journal. Link

Scientific Opinion of the EFSA BIOHAZ Panel (EFSA Journal 2011;9:2393) on risk-based control of biogenic amine formation in fermented foods, a qualitative risk assessment based on the literature, EU surveys and consumption data. Histamine and tyramine are considered the most toxic and food-safety-relevant amines, and fermented foods are of particular concern due to intensive microbial activity. The Panel ranked food categories by histamine and tyramine, but available data were insufficient for a quantitative risk assessment; key mitigation options include hygienic measures and use of non-amine-producing starter cultures.

[1736] FDA. Soft cheeses and Listeria monocytogenes risk. 2023. . 2023. Link

FDA material on the risk of Listeria monocytogenes contamination in soft cheeses.

[1737] Walther B et al. Cheese in nutrition and health2008. Dairy Sci Technol. Link

Review by Walther et al. (Dairy Sci Technol 2008) on the role of cheese in nutrition and health. Cheese is a rich source of proteins, bioactive peptides, amino acids, fat, fatty acids, vitamins and minerals; ripened cheese is lactose-free and thus suitable for lactose-intolerant individuals. Its high calcium content contributes to bone and tooth integrity; the tripeptides VPP and IPP may lower blood pressure, and despite the saturated and trans fatty acid content there is no clear evidence linking cheese consumption to any disease.

[1738] Monash University. Hard cheese FODMAP serving guide (≈ 30–40 g green). Link

Monash University FODMAP data on serving size for hard cheese (≈30–40 g green/safe category).

[1739] EFSA NDA Panel. Scientific opinion on live yoghurt cultures and improved lactose digestion2010;8(10):1763. EFSA Journal. Link

[1740] Wallace TC, Lalonde C, Bourassa MW. Casein satiety: a clinical review 2018. J Food Sci. 2018.

Clinical review on the satiety effects of casein.

[1742] Hill C et al. ISAPP consensus on the term "probiotic"2014;11(8):506–514. Nat Rev Gastroenterol Hepatol. 2014. Link

[1744] Codex Alimentarius. Standard for fermented milks (CXS 243-2003). . 2003. Link

Codex Alimentarius standard for fermented milks (CXS 243-2003).

[1745] EFSA NDA Panel. Scientific opinion on live yoghurt cultures and improved lactose digestion2010;8(10):1763. EFSA Journal. Link

[1746] Wallace TC. Health effects of fermented dairy 2018. J Food Sci. 2018.

Review of the health effects of fermented dairy products.

[1748] Beltrán-Barrientos LM, Hernández-Mendoza A, Torres-Llanez MJ, González-Córdova AF, Vallejo-Córdoba B. Invited review: Fermented milk as antihypertensive functional food2016;99(6):4099–4110. J Dairy Sci. Link

Over the past decade, interest has risen in fermented dairy foods that promote health and could prevent diseases such as hypertension. This biological effect has mainly been attributed to bioactive peptides encrypted within dairy proteins that can be released during fermentation with specific lactic acid bacteria or during gastrointestinal digestion. The most studied bioactive peptides derived from dairy proteins are antihypertensive peptides; however, a need exists to review the different studies dealing with the evaluation of antihypertensive fermented milk before a health claim may be associated with the product. Thus, the objective of this overview was to present available information related to the evaluation of fermented milk containing antihypertensive peptides by in vitro and in vivo studies, which are required before a fermented functional dairy product may be introduced to the market. Although commercial fermented milks with antihypertensive effects exist, these are scarce and most are based on Lactobacillus helveticus. Thus, a great opportunity is available for the development of functional dairy products with new lactic acid bacteria that support heart health through blood pressure- and heart rate-lowering effects.

[1750] Codex Alimentarius. Group standard for unripened cheese including fresh cheese (CXS 221-2001). . 2001. Link

Codex Alimentarius group standard for unripened cheese, including fresh cheese (CXS 221-2001).

[1751] Hill C et al. ISAPP consensus on the term "probiotic"2014;11(8):506–514. Nat Rev Gastroenterol Hepatol. 2014. Link

[1752] Lordan R et al. Dairy fats and cardiovascular disease: do we really need to be concerned?2018;7(3):29. Foods. 2018. Link

Cardiovascular diseases (CVD) remain a major cause of death and morbidity globally and diet plays a crucial role in the disease prevention and pathology. The negative perception of dairy fats stems from the effort to reduce dietary saturated fatty acid (SFA) intake due to their association with increased cholesterol levels upon consumption and the increased risk of CVD development. Institutions that set dietary guidelines have approached dairy products with negative bias and used poor scientific data in the past. As a result, the consumption of dairy products was considered detrimental to our cardiovascular health. In western societies, dietary trends indicate that generally there is a reduction of full-fat dairy product consumption and increased low-fat dairy consumption. However, recent research and meta-analyses have demonstrated the benefits of full-fat dairy consumption, based on higher bioavailability of high-value nutrients and anti-inflammatory properties.

[1753] EFSA NDA Panel. Scientific opinion on live yoghurt cultures and improved lactose digestion2010;8(10):1763. EFSA Journal. Link

[1756] Snijders T et al. Protein ingestion before sleep increases muscle mass and strength gains during prolonged resistance-type exercise training in healthy young men2015;145(6):1178–1184. J Nutr. Link

BACKGROUND: It has been demonstrated that protein ingestion before sleep increases muscle protein synthesis rates during overnight recovery from an exercise bout. However, it remains to be established whether dietary protein ingestion before sleep can effectively augment the muscle adaptive response to resistance-type exercise training. OBJECTIVE: Here we assessed the impact of dietary protein supplementation before sleep on muscle mass and strength gains during resistance-type exercise training. METHODS: Forty-four young men (22 ± 1 y) were randomly assigned to a progressive, 12-wk resistance exercise training program. One group consumed a protein supplement containing 27.5 g of protein, 15 g of carbohydrate, and 0.1 g of fat every night before sleep. The other group received a noncaloric placebo.

[1757] Madzima TA, Panton LB, Fretti SK, Kinsey AW, Ormsbee MJ. Night-time consumption of protein or carbohydrate results in increased morning resting energy expenditure in active college-aged men2014;111(1):71–77. Br J Nutr. Link

The purpose of the present study was to investigate whether whey protein (WP), casein protein (CP), carbohydrate (CHO) or a non-energy-containing placebo (PLA) consumed before sleep alters morning appetite and resting energy expenditure (REE) in active men. A total of eleven men (age: 23·6 (sem 1·0) years; body fat: 16·3 (sem 2·5) \%) participated in this randomised, double-blind, cross-over study. A single dose of WP (30 g), CP (30 g), CHO (33 g) or PLA was consumed 30 min before sleep, and each trial was separated by 48-72 h. The next morning (05.00-08.00 hours), measurements of satiety, hunger and desire to eat and REE were taken. After a 30 min equilibration period, REE in the supine position was measured for 60 min. An analysis of 10 min mean intervals over the final 50 min of the measurement period was conducted.

[1758] Codex Alimentarius. Standard for Cottage Cheese (CXS 273-1968, Rev. 2022). . 1968. Link

Codex Alimentarius standard for Cottage Cheese (CXS 273-1968, Rev. 2022).

[1760] EFSA NDA Panel. Scientific opinion on live yoghurt cultures and improved lactose digestion2010;8(10):1763. EFSA Journal. Link

[1764] Tamime AY, Robinson RK. 3rd ed. Woodhead Publishing, 2007 (general labneh and concentrated fermented milks reference). Yoghurt: Science and Technology. 2007. Link

Reference book (Woodhead Publishing, 3rd ed., 2007) on yoghurt science and technology; general reference for labneh and concentrated fermented milks.

[1766] Hill C et al. ISAPP consensus on the term "probiotic"2014;11(8):506–514. Nat Rev Gastroenterol Hepatol. 2014. Link

[1767] Tang JE et al. Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men2009;107(3):987–992. J Appl Physiol. Link

This study was designed to compare the acute response of mixed muscle protein synthesis (MPS) to rapidly (i.e., whey hydrolysate and soy) and slowly (i.e., micellar casein) digested proteins both at rest and after resistance exercise. Three groups of healthy young men (n = 6 per group) performed a bout of unilateral leg resistance exercise followed by the consumption of a drink containing an equivalent content of essential amino acids (10 g) as either whey hydrolysate, micellar casein, or soy protein isolate. Mixed MPS was determined by a primed constant infusion of l-[ring-(13)C(6)]phenylalanine. Ingestion of whey protein resulted in a larger increase in blood essential amino acid, branched-chain amino acid, and leucine concentrations than either casein or soy (P < 0.05). Mixed MPS at rest (determined in the nonexercised leg) was higher with ingestion of faster proteins (whey = 0.091 +/- 0.015, soy = 0.078 +/- 0.014, casein = 0.047 +/- 0.008\%/h); MPS after consumption of whey was approximately 93\% greater than casein (P < 0.01) and approximately 18\% greater than soy (P = 0.067). A similar result was observed after exercise (whey > soy > casein); MPS following whey consumption was approximately 122\% greater than casein (P < 0.01) and 31\% greater than soy (P < 0.05).

[1768] Phillips SM, Van Loon LJC. Dietary protein for athletes: from requirements to optimum adaptation2011;29(Suppl 1):S29–S38. J Sports Sci. Link

Opinion on the role of protein in promoting athletic performance is divided along the lines of how much aerobic-based versus resistance-based activity the athlete undertakes. Athletes seeking to gain muscle mass and strength are likely to consume higher amounts of dietary protein than their endurance-trained counterparts. The main belief behind the large quantities of dietary protein consumption in resistance-trained athletes is that it is needed to generate more muscle protein. Athletes may require protein for more than just alleviation of the risk for deficiency, inherent in the dietary guidelines, but also to aid in an elevated level of functioning and possibly adaptation to the exercise stimulus. It does appear, however, that there is a good rationale for recommending to athletes protein intakes that are higher than the RDA. Our consensus opinion is that leucine, and possibly the other branched-chain amino acids, occupy a position of prominence in stimulating muscle protein synthesis; that protein intakes in the range of 1.3-1.8 g · kg(-1) · day(-1) consumed as 3-4 isonitrogenous meals will maximize muscle protein synthesis.

[1769] Mignone LE, Wu T, Horowitz M, Rayner CK. Whey protein: the "whey" forward for treatment of type 2 diabetes?2015;6(14):1274–1284. World J Diabetes. 2015. Link

A cost-effective nutritional approach to improve postprandial glycaemia is attractive considering the rising burden of diabetes throughout the world. Whey protein, a by-product of the cheese-making process, can be used to manipulate gut function in order to slow gastric emptying and stimulate incretin hormone secretion, thereby attenuating postprandial glycaemic excursions. The function of the gastrointestinal tract plays a pivotal role in glucose homeostasis, particularly during the postprandial period, and this review will discuss the mechanisms by which whey protein slows gastric emptying and stimulates release of gut peptides, including the incretins. Whey protein is also a rich source of amino acids, and these can directly stimulate beta cells to secrete insulin, which contributes to the reduction in postprandial glycaemia. Appetite is suppressed with consumption of whey, due to its effects on the gut-brain axis and the hypothalamus. These properties of whey protein suggest its potential in the management of type 2 diabetes.

[1770] Marshall K. Therapeutic applications of whey protein2004;9(2):136–156. Altern Med Rev. Link

Whey, a protein complex derived from milk, is being touted as a functional food with a number of health benefits. The biological components of whey, including lactoferrin, beta-lactoglobulin, alpha-lactalbumin, glycomacropeptide, and immunoglobulins, demonstrate a range of immune-enhancing properties. In addition, whey has the ability to act as an antioxidant, antihypertensive, antitumor, hypolipidemic, antiviral, antibacterial, and chelating agent. The primary mechanism by which whey is thought to exert its effects is by intracellular conversion of the amino acid cysteine to glutathione, a potent intracellular antioxidant. A number of clinical trials have successfully been performed using whey in the treatment of cancer, HIV, hepatitis B, cardiovascular disease, osteoporosis, and as an antimicrobial agent. Whey protein has also exhibited benefit in the arena of exercise performance and enhancement.

[1773] Smithers GW. Whey and whey proteins — from "gutter-to-gold."2008;18(7):695–704. Int Dairy J. 2008. Link

Review by Smithers (Int Dairy J 2008) on the valorisation of whey and whey proteins (the 'gutter-to-gold' journey of the title). Once regarded as waste, whey became a valuable raw material following environmental regulation and advances in science; whey proteins (e.g. beta-lactoglobulin, alpha-lactalbumin, lactoferrin) possess important nutritional and functional properties and have many applications in the food industry and in health promotion.

[1774] Madureira AR et al. Bovine whey proteins — overview on their main biological properties2007;40(10):1197–1211. Food Res Int. Link

Review by Madureira et al. (Food Res Int 2007) on the main biological properties of bovine whey proteins. The major whey proteins (beta-lactoglobulin, alpha-lactalbumin, serum albumin, immunoglobulins, lactoferrin, lactoperoxidase) display a range of health-promoting effects, including antimicrobial and antiviral action, stimulation of the immune system, anticarcinogenic activity and other metabolic features.

[1775] Yang CS et al. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance2009. Nat Rev Cancer. Link

Extracts of tea, especially green tea, and tea polyphenols have been shown to inhibit the formation and development of tumours at different organ sites in animal models. There is considerable evidence that tea polyphenols, in particular (-)-epigallocatechin-3-gallate, inhibit enzyme activities and signal transduction pathways, resulting in the suppression of cell proliferation and enhancement of apoptosis, as well as the inhibition of cell invasion,angiogenesis and metastasis. Here, we review these biological activities and existing data relating tea consumption to human cancer risk in an attempt to understand the potential use of tea for cancer prevention.

[1776] Ohishi T et al. Anti-inflammatory action of green tea2016. Antiinflamm Antiallergy Agents Med Chem. Link

BACKGROUND: Green tea has been shown to have beneficial effects against a variety of diseases such as cancer, obesity, diabetes, cardiovascular disease, and neurodegenerative diseases. Through cellular, animal, and human experiments, green tea and its major component, epigallocatechin-3-gallate (EGCG) have been demonstrated to have anti-inflammatory effects. Our previous findings have indicated that green tea and EGCG suppress the gene and/or protein expression of inflammatory cytokines and inflammation-related enzymes. METHODS: Using bibliographic databases, particularly PubMed (provided by the http://www.ncbi.nlm.nih.gov/pubmed, US National Library of Medicine, National Institutes of Health, United States), we examined the potential usefulness of green tea/EGCG for the prevention and treatment of inflammatory diseases in human clinical and epidemiological studies. We also reviewed results from cellular and animal experiments and proposed action mechanisms. RESULTS: Most of the results from the human studies indicated the beneficial effects of green tea and tea catechins against inflammatory diseases.

[1777] EFSA Panel. Scientific opinion on the safety of green tea catechins2018. EFSA Journal. Link

The EFSA ANS Panel was asked to provide a scientific opinion on the safety of green tea catechins from dietary sources including preparations such as food supplements and infusions. Green tea is produced from the leaves of Camellia sinensis (L.) Kuntze, without fermentation, which prevents the oxidation of polyphenolic components. Most of the polyphenols in green tea are catechins. The Panel considered the possible association between the consumption of (-)-epigallocatechin-3-gallate (EGCG), the most relevant catechin in green tea, and hepatotoxicity. This scientific opinion is based on published scientific literature, including interventional studies, monographs and reports by national and international authorities and data received following a public 'Call for data'. The mean daily intake of EGCG resulting from the consumption of green tea infusions ranges from 90 to 300 mg/day while exposure by high-level consumers is estimated to be up to 866 mg EGCG/day, in the adult population in the EU.

[1778] Morita Y et al. A randomized, double-blinded study evaluating effect of matcha green tea on human fecal microbiota2023;72(2):165–171. J Clin Biochem Nutr. Link

Randomized, double-blinded study evaluating the effect of matcha green tea on human fecal microbiota.

[1779] Auvichayapat P et al. Effectiveness of green tea on weight reduction in obese Thais2008. Physiol Behav. Link

This study was undertaken to investigate the effects of green tea on weight reduction in obese Thais. A randomized, controlled trial involving 60 obese subjects (body mass index, BMI > 25 kg/m2) was conducted. All subjects consumed a Thai diet containing 3 meals (8373.6 kJ/day) for 12 weeks, prepared by the Nutritional Unit at Srinagarind Hospital. The diet contained 65\% carbohydrates, 15\% protein, and 20\% fat. Body weight, BMI, body composition, resting energy expenditure, and substrate oxidation were measured at baseline, and during weeks 4, 8, and 12 of the study. Serum levels of leptin and urine VMA were measured at baseline and during the 12th week.

[1780] Shoji T et al. Bioavailability of tea catechins after consumption of green tea — review 2014. Curr Pharm Biotechnol. 2014.

Review on the bioavailability of tea catechins after green tea consumption.

[1781] EMA/HMPC. Camellia sinensis monograph. 2018. . 2018. Link

EMA/HMPC herbal monograph on Camellia sinensis.

[1782] Liu Z et al. Tea polyphenols and gut microbiota: review 2022. Crit Rev Food Sci Nutr. 2022.

Review of tea polyphenols and gut microbiota interactions.

[1783] Mou Q et al. Black tea polyphenols and gut microbiota — human RCT 2018. Food Funct. 2018.

Human randomized controlled trial (RCT) on black tea polyphenols and gut microbiota.

[1784] Hartley L et al. Green and black tea for the primary prevention of cardiovascular disease2013. Cochrane Database Syst Rev. Link

BACKGROUND: There is increasing evidence that both green and black tea are beneficial for cardiovascular disease (CVD) prevention. OBJECTIVES: To determine the effects of green and black tea on the primary prevention of CVD. SEARCH METHODS: We searched the following databases on 12 October 2012 without language restrictions: CENTRAL in The Cochrane Library, MEDLINE (OVID), EMBASE (OVID) and Web of Science (Thomson Reuters). We also searched trial registers, screened reference lists and contacted authors for additional information where necessary. SELECTION CRITERIA: Randomised controlled trials (RCTs) lasting at least three months involving healthy adults or those at high risk of CVD. Trials investigated the intake of green tea, black tea or tea extracts.

[1785] Liu G et al. Habitual tea consumption and risk of coronary heart disease — meta-analysis 2014. Br J Nutr. 2014.

Meta-analysis on habitual tea consumption and risk of coronary heart disease.

[1786] Lorenz M et al. Addition of milk prevents vascular protective effects of tea2007. Eur Heart J. Link

AIMS: Experimental and clinical studies indicate that tea exerts protection against cardiovascular diseases. However, a question of much debate is whether addition of milk modifies the biological activities of tea. We studied the vascular effects of tea, with or without milk, in humans and elucidated the impact of individual milk proteins in cell culture experiments, with isolated rat aortic rings and by HPLC analysis. METHODS AND RESULTS: A total of 16 healthy female volunteers consumed either 500 mL of freshly brewed black tea, black tea with 10\% skimmed milk, or boiled water as control. Flow-mediated dilation (FMD) was measured by high-resolution vascular ultrasound before and 2 h after consumption. Black tea significantly improved FMD in humans compared with water, whereas addition of milk completely blunted the effects of tea.

[1787] Khan N, Mukhtar H. Tea polyphenols in promotion of human health2018;11(1):39. Nutrients. Link

Tea is the most widely used beverage worldwide. Japanese and Chinese people have been drinking tea for centuries and in Asia, it is the most consumed beverage besides water. It is a rich source of pharmacologically active molecules which have been implicated to provide diverse health benefits. The three major forms of tea are green, black and oolong tea based on the degree of fermentation. The composition of tea differs with the species, season, leaves, climate, and horticultural practices. Polyphenols are the major active compounds present in teas.

[1788] Kyle JA et al. Effects of infusion time and addition of milk on content and absorption of polyphenols from black tea2007. J Agric Food Chem. Link

Epidemiological studies assessing the health benefits of drinking black tea are equivocal. Such disparity may reflect an inability of semiquantitative assessment to consider how infusion time and addition of milk affect the bioavailability of potentially beneficial antioxidant polyphenols. Six brands of tea demonstrated similar increases in antioxidant capacity and total phenolic and catechin contents with increasing infusion time. These results were unaffected by the addition of milk. Consumption of black tea (400 mL) was associated with significant increases in plasma antioxidant capacity (10\%) and concentrations of total phenols (20\%), catechins (32\%), and the flavonols quercetin (39\%) and kaempferol (45\%) (all p < 0.01) within 80 min. This was unaffected by adding milk.

[1789] Liu Z et al. Tea polyphenols and gut microbiota interactions 2022. Crit Rev Food Sci Nutr. 2022.

Review of tea polyphenols and gut microbiota interactions.

[1790] Yan Z et al. Theaflavin in black tea and human health 2020. Trends Food Sci Technol. 2020.

Review on theaflavin in black tea and human health.

[1791] Brown OI et al. Effect of coffee on distal colon function1990;31(4):450–453. Gut. Link

Human study (Gut) on the effect of coffee on distal colon function.

[1792] Jaquet M et al. Impact of coffee consumption on the gut microbiota — RCT2009. Int J Food Microbiol. Link

The impact of a moderate consumption of an instant coffee on the general composition of the human intestinal bacterial population was assessed in this study. Sixteen (16) healthy adult volunteers consumed a daily dose of 3 cups of coffee during 3 weeks. Faecal samples were collected before and after the consumption of coffee, and the impact of the ingestion of the product on the intestinal bacteria as well as the quantification of specific bacterial groups was assessed using nucleic acid-based methods. Although faecal profiles of the dominant microbiota were not significantly affected after the consumption of the coffee (Dice's similarity index=92\%, n=16), the population of Bifidobacterium spp. increased after the 3-week test period (P=0.02). Moreover, in some subjects, there was a specific increase in the metabolic activity of Bifidobacterium spp. Our results show that the consumption of the coffee preparation resulting from water co-extraction of green and roasted coffee beans produce an increase in the metabolic activity and/or numbers of the Bifidobacterium spp. population, a bacterial group of reputed beneficial effects, without major impact on the dominant microbiota.

[1793] Asnicar F et al. Microbiome connections with host metabolism — coffee in n=22,000 metagenomes2024. Nat Med. Link

The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements were available. We found many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism, overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and postprandial glycemic, lipemic and inflammatory indices. The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without clinically manifest disease.

[1794] Poole R et al. Coffee consumption and health: umbrella review of meta-analyses2017;359:j5024. BMJ. Link

Objectives To evaluate the existing evidence for associations between coffee consumption and multiple health outcomes.Design Umbrella review of the evidence across meta-analyses of observational and interventional studies of coffee consumption and any health outcome.Data sources PubMed, Embase, CINAHL, Cochrane Database of Systematic Reviews, and screening of references.Eligibility criteria for selecting studies Meta-analyses of both observational and interventional studies that examined the associations between coffee consumption and any health outcome in any adult population in all countries and all settings. Studies of genetic polymorphisms for coffee metabolism were excluded.Results The umbrella review identified 201 meta-analyses of observational research with 67 unique health outcomes and 17 meta-analyses of interventional research with nine unique outcomes. Coffee consumption was more often associated with benefit than harm for a range of health outcomes across exposures including high versus low, any versus none, and one extra cup a day. There was evidence of a non-linear association between consumption and some outcomes, with summary estimates indicating largest relative risk reduction at intakes of three to four cups a day versus none, including all cause mortality (relative risk 0.83 (95\% confidence interval 0.79 to 0.88), cardiovascular mortality (0.81, 0.72 to 0.90), and cardiovascular disease (0.85, 0.80 to 0.90). High versus low consumption was associated with an 18\% lower risk of incident cancer (0.82, 0.74 to 0.89). Consumption was also associated with a lower risk of several specific cancers and neurological, metabolic, and liver conditions.

[1795] EFSA. Scientific opinion on the safety of caffeine2015;13(5):4102. EFSA Journal. Link

Scientific Opinion of the EFSA NDA Panel on the safety of caffeine (EFSA Journal 2015;13:4102), assessing caffeine intake from all dietary sources. The Panel concluded that single doses up to 200 mg (about 3 mg/kg bw for a 70-kg adult) and habitual intakes up to 400 mg/day do not raise safety concerns for non-pregnant adults; for pregnant and lactating women habitual intakes up to 200 mg/day do not raise concerns for the fetus or breastfed infant; for children and adolescents the available data are insufficient to derive a safe intake.

[1796] Cornelis MC et al. Coffee, CYP1A2 genotype and risk of myocardial infarction2006. JAMA. Link

CONTEXT: The association between coffee intake and risk of myocardial infarction (MI) remains controversial. Coffee is a major source of caffeine, which is metabolized by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. Individuals who are homozygous for the CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers. OBJECTIVE: To determine whether CYP1A2 genotype modifies the association between coffee consumption and risk of acute nonfatal MI. DESIGN, SETTING, AND PARTICIPANTS: Cases (n = 2014) with a first acute nonfatal MI and population-based controls (n = 2014) living in Costa Rica between 1994 and 2004, matched for age, sex, and area of residence, were genotyped by restriction fragment-length polymorphism polymerase chain reaction. A food frequency questionnaire was used to assess the intake of caffeinated coffee.

[1797] Mendoza-Aguilar JM et al. Coffee melanoidins as dietary fiber 2022. Trends Food Sci Technol. 2022.

Review on coffee melanoidins as dietary fiber.

[1798] Liu G et al. Chlorogenic acid and gut microbiota: review 2023. Crit Rev Food Sci Nutr. 2023.

Review of chlorogenic acid and gut microbiota.

[1799] EFSA Panel. Scientific Opinion on chicory inulin and maintenance of normal defecation2015;13(1):3951. EFSA Journal. Link

Scientific Opinion of the EFSA NDA Panel (EFSA Journal 2015;13:3951) on the substantiation of a health claim relating 'native chicory inulin' to maintenance of normal defecation by increasing stool frequency, under Article 13.5. Six studies involving 86 subjects consistently showed that consumption of at least 12 g/day of native chicory inulin increases stool frequency; the Panel established a cause-and-effect relationship, with 12 g/day required to obtain the effect.

[1800] Kolida S, Tuohy K, Gibson GR. Prebiotic effects of inulin and oligofructose2002;87(Suppl 2):S193–S197. Br J Nutr. Link

Prebiotics are non-digestible food ingredients that target certain components within the microbiota of the human large intestine. Efficient prebiotics need to have a specific fermentation therein and thereby have the ability to alter the faecal microflora composition towards a more 'beneficial' community structure. This should occur by the stimulation of benign or potentially health promoting genera but not the harmful groups. Because of their positive attributes bifidobacteria and lactobacilli are the most frequent target organisms. Both inulin and oligofructose have been demonstrated to be effective prebiotics. This has been shown through both in vitro and in vivo assessments in different laboratories.

[1801] Janda K et al. Chicory ( L.) — biological activity. Foods 2021;10(7):1641. Cichorium intybus. 2021.

Review on the biological activity of chicory (Cichorium intybus L.).

[1802] Innocenti G et al. Phenolic compounds in roasted chicory2005. J Agric Food Chem. Link

Fresh aerial parts of different chicory varieties: green chicory (c.v. "Catalogna"), two red chicory varieties ("radicchio rosso di Chioggia" and "radicchio rosso di Treviso"), and Witloof or Belgian endive were analyzed by HPLC/DAD/MS. The chromatographic fingerprint was diagnostic for each variety. A monocaffeoyl tartaric acid, chlorogenic acid, and chicoric acid were detected in all the varieties, while cyanidin 3-O-glucoside, delphinidin 3-O-(6'' malonyl) glucoside, and cyanidin 3-O-(6'' malonyl) glucoside were the main phenolic compounds in the red varieties. The flavonoidic compounds, quercetin 3-O-glucuronide and luteolin 7-O-glucuronide, were absent in the Witloof sample. The phenolic compounds from total leaves were the same as those obtained from only the colored parts; nevertheless, the total amount was remarkably lower with a decrease of up to 80\% for Belgian endive. Chemical stability at high temperature was observed for the phenolic fraction from the green variety after decoction at 100 degrees C for 30 min.

[1803] Slavin J. Fiber and prebiotics: mechanisms and health benefits2013. Nutrients. Link

The health benefits of dietary fiber have long been appreciated. Higher intakes of dietary fiber are linked to less cardiovascular disease and fiber plays a role in gut health, with many effective laxatives actually isolated fiber sources. Higher intakes of fiber are linked to lower body weights. Only polysaccharides were included in dietary fiber originally, but more recent definitions have included oligosaccharides as dietary fiber, not based on their chemical measurement as dietary fiber by the accepted total dietary fiber (TDF) method, but on their physiological effects. Inulin, fructo-oligosaccharides, and other oligosaccharides are included as fiber in food labels in the US. Additionally, oligosaccharides are the best known "prebiotics", "a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-bring and health." To date, all known and suspected prebiotics are carbohydrate compounds, primarily oligosaccharides, known to resist digestion in the human small intestine and reach the colon where they are fermented by the gut microflora.

[1804] EMA/HMPC. Cichorium intybus L., radix — herbal monograph. 2020. . 2020. Link

EMA/HMPC herbal monograph on chicory root (Cichorium intybus L., radix).

[1805] Wilson R, Komitopoulou E. Functional properties of chicory melanoidins 2018. Food Funct. 2018.

Study on the functional properties of chicory melanoidins.

[1807] Huang HC et al. Pu-erh tea ameliorates hyperlipidemia: a randomized, double-blind, placebo-controlled clinical trial. Phytomedicine 2014;21(11):1456–1462. . 2014.

Randomized, double-blind, placebo-controlled clinical trial on pu-erh tea in hyperlipidemia.

[1808] Jeng KC et al. Effect of microbial fermentation on content of statin, GABA and polyphenols in pu-erh tea. J Agric Food Chem 2007;55(21):8787–8792. . 2007. Link

Besides cancer prevention, the hypolipidemic effects of tea have been well studied in animals and humans. Recently, statin has been identified in Pu-erh tea extract. Clinical trials have confirmed that statin decreases the incidence of major coronary and cerebrovascular events and this may be due to its hypolipidemic and antiinflammatory effects. Since a good Pu-erh tea needs longer storage (10 years or more) of fermentation to enhance the flavor and fragrance, we screened microorganisms from two Pu-erh teas, 20 and 25 years old. Species of fungi and bacteria strains that contributed to a good taste of Pu-erh tea were isolated. The effect of fermentation was investigated by inoculating fresh tea leaves with individual strains of isolated microorganisms.

[1809] Ahmed S, Stepp JR. Pu-erh tea — botany, production and chemistry. Tea in Health and Disease Prevention 2013 (Academic Press). . 2013. Link

Book chapter by Ahmed and Stepp (Tea in Health and Disease Prevention, Academic Press 2013) on the botany, production and chemistry of pu-erh tea. Pu-erh is made from processed leaves and buds of the broad-leaf variety of the tea plant (Camellia sinensis var. assamica), mainly from Yunnan province, China; it may be produced as loose or pressed green tea or as a post-fermented (aged) black tea. Fresh green pu-erh has health claims similar to other green teas, while aged and post-fermented pu-erh gains additional claims through new compounds formed during microbial fermentation, characteristic of fermented foods.

[1810] Wang Q et al. Pu-erh tea and lipid metabolism: systematic review and meta-analysis. J Funct Foods 2020;72:104077. . 2020.

Systematic review and meta-analysis on pu-erh tea and lipid metabolism.

[1811] Lv HP et al. Processing and chemical constituents of pu-erh tea — a review. Food Res Int 2013;53(2):608–618. . 2013. Link

Review by Lv et al. (Food Res Int 2013) on the processing and chemical constituents of pu-erh tea. The article summarises the tea's chemical composition, processing methods and processing-induced chemical transformations; during post-fermentation, extracellular enzymes from microorganisms catalyse the oxidation, condensation and degradation of tea constituents, producing the characteristic sensory properties of pu-erh.

[1812] Loomis D et al. (IARC Monograph WG). Carcinogenicity of drinking coffee, mate, and very hot beverages. Lancet Oncol 2016;17(7):877–878. . 2016. Link

Summary of the IARC Monographs (Volume 116) Working Group evaluation (Loomis et al., Lancet Oncol 2016) on the carcinogenicity of coffee, mate and very hot beverages, based on review of over 1000 human and animal studies. The Group found inadequate evidence for carcinogenicity of coffee drinking overall, while drinking very hot beverages (above ~65 C) was classified as probably carcinogenic to humans (Group 2A), based on limited evidence of an association with oesophageal cancer.

[1813] Cabrera C et al. Beneficial effects of green tea — a review. J Am Coll Nutr 2006;25(2):79–99. . 2006. Link

Tea is the most consumed drink in the world after water. Green tea is a 'non-fermented' tea, and contains more catechins, than black tea or oolong tea. Catechins are in vitro and in vivo strong antioxidants. In addition, its content of certain minerals and vitamins increases the antioxidant potential of this type of tea. Since ancient times, green tea has been considered by the traditional Chinese medicine as a healthful beverage. Recent human studies suggest that green tea may contribute to a reduction in the risk of cardiovascular disease and some forms of cancer, as well as to the promotion of oral health and other physiological functions such as anti-hypertensive effect, body weight control, antibacterial and antivirasic activity, solar ultraviolet protection, bone mineral density increase, anti-fibrotic properties, and neuroprotective power.

[1814] Hou Y et al. Microbial fermentation of pu-erh tea — impact on gut microbiota. mSystems 2021;6(4):e00396-21. . 2021.

Study on microbial fermentation of pu-erh tea and its impact on gut microbiota.

[1815] Hilal Y, Engelhardt U. Characterisation of white tea — comparison to green and black tea. J Verbraucherschutz Lebensmittelsicherh 2007;2:414–421. . 2007. Link

Hilal and Engelhardt (J Verbraucherschutz Lebensmittelsicherh 2007) characterised white tea in comparison to green and black tea; the study describes the manufacture of the tea types, the main phenolic compounds and analytical methods, and presents compositional data for 30 black, 30+30 green and 30 white teas. The ratio between total phenolics and the sum of the major catechins allowed differentiation of green from black tea, but green and white teas could not be distinguished by this ratio.

[1816] Cabrera C et al. Beneficial effects of green tea — review. J Am Coll Nutr 2006;25(2):79–99. . 2006. Link

[1817] Santana-Rios G et al. Potent antimutagenic activity of white tea in comparison with green tea. Mutat Res 2001;495(1–2):61–74. . 2001. Link

There is growing interest in the potential health benefits of tea, including the antimutagenic properties. Four varieties of white tea, which represent the least processed form of tea, were shown to have marked antimutagenic activity in the Salmonella assay, particularly in the presence of S9. The most active of these teas, Exotica China white tea, was significantly more effective than Premium green tea (Dragonwell special grade) against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and four other heterocyclic amine mutagens, namely 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mechanism studies were performed using rat liver S9 in assays for methoxyresorufin O-demethylase (MROD), a marker for the enzyme cytochrome P4501A2 that activates heterocyclic amines, as well as Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). White tea at low concentrations in the assay inhibited MROD activity, and attenuated the mutagenic activity of N-hydroxy-IQ in the absence of S9. Nine of the major constituents found in green tea also were detected in white tea, including high levels of epigallocatechin-3-gallate (EGCG) and several other polyphenols.

[1818] Camouse MM et al. Topical application of green and white tea extracts provides protection from solar-simulated UV light. Exp Dermatol 2009;18(6):522–526. . 2009. Link

BACKGROUND: Tea polyphenols have been found to exert beneficial effects on the skin via their antioxidant properties. AIMS: We sought to determine whether topical application of green tea or white tea extracts would prevent simulated solar radiation-induced oxidative damages to DNA and Langerhans cells that may lead to immune suppression and carcinogenesis. METHODS: Skin samples were analysed from volunteers or skin explants treated with white tea or green tea after UV irradiation. In another group of patients, the in vivo immune protective effects of green and white tea were evaluated using contact hypersensitivity to dinitrochlorobenzene. RESULTS: Topical application of green and white tea offered protection against detrimental effects of UV on cutaneous immunity. Such protection is not because of direct UV absorption or sunscreen effects as both products showed a sun protection factor of 1.

[1819] Mazzanti G et al. Hepatotoxicity from green tea — review. Drug Saf 2015;38(8):765–774. . 2015. Link

Green tea (GT), obtained from the leaves of Camellia sinensis (L.) Kuntze (Fam. Theaceae), is largely used for its potential health benefits such as reduction in risk of cardiovascular diseases and weight loss. Nevertheless, it is suspected to induce liver damage. Present work reviews the hepatic adverse reactions associated with GT-based herbal supplements, published by the end of 2008 to March 2015. A systematic research was carried out on PubMed, MedlinePlus, Scopus and Google Scholar databases, without any language restriction. Moreover, some accessible databases on pharmacovigilance or phytovigilance were consulted.

[1820] EFSA Panel on Food Additives. Scientific opinion on the safety of green tea catechins. EFSA J 2018;16(4):5239. . 2018. Link

[1821] Loomis D et al. (IARC). Carcinogenicity of drinking very hot beverages. Lancet Oncol 2016;17(7):877–878. . 2016. Link

[1822] Yuan JM. Cancer prevention by tea — humans. Mol Nutr Food Res 2011;55(6):886–904. . 2011. Link

Green tea contains high concentrations of tea polyphenols that have shown inhibitory effects against the development, progress, and growth of carcinogen-induced tumors in animal models at different organ sites, including the esophagus and lung. Green tea polyphenols also have shown to suppress cell proliferation and induce apoptosis. Besides antioxidative property, green tea polyphenols have pro-oxidative activities under certain conditions and modulate phase II metabolic enzymes that can enhance the detoxification pathway of environmental toxicants and carcinogens. Although epidemiological studies have provided inconclusive results on the effect of green tea consumption against the development of esophageal and lung cancers in humans overall, the inverse association between green tea intake and risk of esophageal cancer risk is more consistently observed in studies with adequate control for potential confounders. Epidemiological studies also have demonstrated an inverse, albeit moderate, association between green tea consumption and lung cancer, especially in non-smokers. This article reviews data on the cancer-preventive activities of green tea extract and green tea polyphenols and possible mechanisms against the esophageal and lung carcinogenesis in experimental animals, and summarizes the current knowledge from epidemiological studies on the relationship between green tea consumption and esophageal and lung cancer risk in humans.

[1823] Mozaffari-Khosravi H et al. The effects of sour tea (Hibiscus sabdariffa) on hypertension in patients with type II diabetes. J Hum Hypertens 2009;23(1):48–54. . 2009. Link

To compare the antihypertensive effectiveness of sour tea (ST; Hibiscus sabdariffa) with black tea (BT) infusion in diabetic patients, this double-blind randomized controlled trial was carried out. Sixty diabetic patients with mild hypertension, without taking antihypertensive or antihyperlipidaemic medicines, were recruited in the study. The patients were randomly allocated to the ST and BT groups and instructed to drink ST and BT infusions two times a day for 1 month. Their blood pressure (BP) was measured on days 0, 15 and 30 of the study. The mean of systolic BP (SBP) in the ST group decreased from 134.4+/-11.8 mm Hg at the beginning of the study to 112.7+/-5.7 mm Hg after 1 month (P-value <0.001), whereas this measure changed from 118.6+/-14.9 to 127.3+/-8.7 mm Hg (P-value=0.002) in the BT group during the same period. The intervention had no statistically significant effect on the mean of diastolic BP (DBP) in either the ST or BT group.

[1824] McKay DL et al. Hibiscus sabdariffa L. tea lowers blood pressure in prehypertensive and mildly hypertensive adults. J Nutr 2010;140(2):298–303. . 2010. Link

In vitro studies show Hibiscus sabdariffa L., an ingredient found in many herbal tea blends and other beverages, has antioxidant properties, and, in animal models, extracts of its calyces have demonstrated hypocholesterolemic and antihypertensive properties. Our objective in this study was to examine the antihypertensive effects of H. sabdariffa tisane (hibiscus tea) consumption in humans. A randomized, double-blind, placebo-controlled clinical trial was conducted in 65 pre- and mildly hypertensive adults, age 30-70 y, not taking blood pressure (BP)-lowering medications, with either 3 240-mL servings/d of brewed hibiscus tea or placebo beverage for 6 wk. A standardized method was used to measure BP at baseline and weekly intervals. At 6 wk, hibiscus tea lowered systolic BP (SBP) compared with placebo (-7.2 +/- 11.4 vs. -1.3 +/- 10.0 mm Hg; P = 0.030). Diastolic BP was also lower, although this change did not differ from placebo (-3.1 +/- 7.0 vs. -0.5 +/- 7.5 mm Hg; P = 0.160).

[1825] Serban C et al. Effect of sour tea (Hibiscus sabdariffa) on arterial hypertension: a systematic review and meta-analysis. J Hypertens 2015;33(6):1119–1127. . 2015. Link

BACKGROUND: Hibiscus sabdariffa L. is a tropical wild plant rich in organic acids, polyphenols, anthocyanins, polysaccharides, and volatile constituents that are beneficial for the cardiovascular system. Hibiscus sabdariffa beverages are commonly consumed to treat arterial hypertension, yet the evidence from randomized controlled trials (RCTs) has not been fully conclusive. Therefore, we aimed to assess the potential antihypertensive effects of H. sabdariffa through systematic review of literature and meta-analysis of available RCTs. METHODS: The search included PUBMED, Cochrane Library, Scopus, and EMBASE (up to July 2014) to identify RCTs investigating the efficacy of H. sabdariffa supplementation on SBP and DBP values. Two independent reviewers extracted data on the study characteristics, methods, and outcomes. Quantitative data synthesis and meta-regression were performed using a fixed-effect model, and sensitivity analysis using leave-one-out method.

[1826] Wahabi HA et al. The effectiveness of Hibiscus sabdariffa in the treatment of hypertension: a systematic review. Phytomedicine 2010;17(2):83–86. . 2010. Link

INTRODUCTION: Hypertension is a common global health problem with significant mortality and morbidity. Hibiscus sabdariffa is a plant known in many countries and is consumed as hot and cold drinks In addition to its use in folk medicine; it has been suggested as treatment for many conditions including hypertension. OBJECTIVES: The objectives of this review were to examine the evidence of effectiveness and safety of hibiscus in the treatment of hypertension. METHODS: We searched several medical databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and the specialized register of the Cochrane Hypertension Group and the general engine Google) to January 2009. We included randomized controlled trials that had examined Hibiscus's effectiveness and safety in the treatment of primary hypertension in adults. Two authors independently selected the trials for the review, extracted the data, and critically appraised the included studies.

[1827] Kolawole JA, Maduenyi A. Effect of zobo drink (Hibiscus sabdariffa) on the pharmacokinetics of acetaminophen. Eur J Drug Metab Pharmacokinet 2004;29(1):25–29. . 2004. Link

Acetaminophen, a common antipyretic-analgesic OTC drug is often administered orally anytime of the day with water or beverages irrespective of possible interactions. Zobo drink, is a sweetened water extract of the dried calyx of Hibiscus Sabdariffa. This work is designed to investigate the effect of zobo drink on an oral dose of acetaminophen. Six healthy male volunteers, ages 28.50 +/- 1.76 years, weighing 62.67 +/- 1.67kg participated in the study. The study was carried out in two phases. In the first phases an oral dose of acetaminophen (1g) was administered to the volunteers and in the second phases, zobo drink was ingested by the volunteers 1.30 h prior the administration of acetaminophen (1g).

[1828] Mahmoud BM et al. Significant reduction in chloroquine bioavailability following coadministration with Hibiscus sabdariffa. J Antimicrob Chemother 1994;33(5):1005–1009. . 1994. Link

Chloroquine bioavailability in healthy males was examined following oral coadministration of 600 mg with three common Sudanese beverages, Aradaib (Tamarindus indica), Karkadi (Hibiscus sabdarifa) and Lemon (Citrus limetta) and drinking water. The tablets and beverages were taken on an empty stomach after an overnight fast. The plasma chloroquine concentrations were measured by HPLC. The extent and rate of chloroquine bioavailability were described by the area under the plasma concentrations versus time curve (AUC), the peak plasma concentration (Cmax) and with the time to reach Cmax (Tmax), respectively. The mean (+/- S.E.) AUC values after administration with water (control) and Aradaib, Karkadi and Lemon, respectively, were 7.52 +/- 0.87, 2.60 +/- 0.24, 2.16 +/- 0.30 and 2.41 +/- 0.29 mg.h/L. The corresponding mean Cmax values were 553 +/- 17.8, 184 +/- 21.3, 148 +/- 14.1 and 210 +/- 17.4 mg/L and the corresponding Tmax values were 3.0 +/- 1.0, 3.2 +/- 1.2, 2.6 +/- 0.8 and 2.5 +/- 1.0 h.

[1829] Da-Costa-Rocha I et al. Hibiscus sabdariffa L. — a phytochemical and pharmacological review. Food Chem 2014;165:424–443. . 2014. Link

Hibiscus sabdariffa L. (Hs, roselle; Malvaceae) has been used traditionally as a food, in herbal drinks, in hot and cold beverages, as a flavouring agent in the food industry and as a herbal medicine. In vitro and in vivo studies as well as some clinical trials provide some evidence mostly for phytochemically poorly characterised Hs extracts. Extracts showed antibacterial, anti-oxidant, nephro- and hepato-protective, renal/diuretic effect, effects on lipid metabolism (anti-cholesterol), anti-diabetic and anti-hypertensive effects among others. This might be linked to strong antioxidant activities, inhibition of α-glucosidase and α-amylase, inhibition of angiotensin-converting enzymes (ACE), and direct vaso-relaxant effect or calcium channel modulation. Phenolic acids (esp. protocatechuic acid), organic acid (hydroxycitric acid and hibiscus acid) and anthocyanins (delphinidin-3-sambubioside and cyanidin-3-sambubioside) are likely to contribute to the reported effects. More well designed controlled clinical trials are needed which use phytochemically characterised preparations.

[1830] EMA/HMPC. Assessment report on Hibiscus sabdariffa L., flos. 2016. . 2016. Link

EMA/HMPC assessment report on Hibiscus sabdariffa L., flos.

[1831] Marnewick JL et al. Effects of rooibos on oxidative stress and biochemical parameters in adults at risk for cardiovascular disease. J Ethnopharmacol 2011;133(1):46–52. . 2011. Link

ETHNOPHARMACOLOGICAL RELEVANCE: In South Africa, the plant Aspalathus linearis (Brum.f) Dahlg. (Fabaceae) is traditionally used as a "tea" referred to as rooibos or redbush. This plant has been listed as a medicinal plant based mostly on anecdotal evidence. AIMS OF THE STUDY: Despite a long history of traditional use in South Africa, very little scientific data are available from controlled clinical trials confirming its popular use. The aim of the present study was to investigate the effect of rooibos on biochemical and oxidative stress parameters in adults at risk for cardiovascular disease. MATERIALS AND METHODS: After a washout period of 2 weeks, 40 volunteers consumed six cups of fermented/traditional rooibos daily for 6 weeks, followed by a control period. Blood biochemical parameters indicative of antioxidant activity and content (total polyphenols), lipid peroxidation (conjugated dienes - CDs, thiobarbituric acid reactive substances - TBARS), redox status (total glutathione - tGSH, ratio of reduced to oxidized glutathione - GSH:GSSG), lipid profile (total cholesterol, low density lipoprotein - LDL and high density lipoprotein - HDL cholesterol and triacylglycerol levels) and liver and kidney function were measured at the end of each study period.

[1832] Beltrán-Debón R et al. Continuous administration of polyphenols from aqueous rooibos extract reduces cardiovascular risk markers. Phytomedicine 2011;18(5):414–424. . 2011. Link

The incidence of obesity and related metabolic diseases is increasing globally. Current medical treatments often fail to halt the progress of such disturbances, and plant-derived polyphenols are increasingly being investigated as a possible way to provide safe and effective complementary therapy. Rooibos (Aspalathus linearis) is a rich source of polyphenols without caloric and/or stimulant components. We have tentatively characterized 25 phenolic compounds in rooibos extract and studied the effects of continuous aqueous rooibos extract consumption in mice. The effects of this extract, which contained 25\% w/w of total polyphenol content, were negligible in animals with no metabolic disturbance but were significant in hyperlipemic mice, especially in those in which energy intake was increased via a Western-type diet that increased the risk of developing metabolic complications. In these mice, we found hypolipemiant activity when given rooibos extract, with significant reductions in serum cholesterol, triglyceride and free fatty acid concentrations.

[1833] Persson IA et al. Effects of green tea, black tea and rooibos tea on angiotensin-converting enzyme and nitric oxide in healthy volunteers. Public Health Nutr 2010;13(5):730–737. . 2010. Link

OBJECTIVE: Tea has been reported to reduce cardiovascular mortality, but the underlying mechanisms are largely unknown. The aim of the current project was to investigate the effect of green tea (Japanese Sencha), black tea (Indian Assam B.O.P.) and Rooibos tea (South Africa) on angiotensin-converting enzyme (ACE) and nitric oxide (NO). DESIGN: Seventeen healthy volunteers received a single oral dose of 400 ml green tea, black tea or Rooibos tea in a randomized, three-phase, crossover study. ACE activity and NO concentration were measured (at 0, 30, 60 and 180 min) in all phases. ACE activity was analysed by means of a commercial radioenzymatic assay. Nitrite was analysed as a marker of NO concentration.

[1834] Mathijs I et al. Phenylpropenoic acid glucoside augments pancreatic beta cell mass and improves glucose tolerance. Phytother Res 2014. . 2014.

Study on phenylpropenoic acid glucoside affecting pancreatic beta cell mass and glucose tolerance.

[1835] Kawano A et al. Hypoglycemic effect of aspalathin, a rooibos tea component. Phytomedicine 2009;16(5):437–443. . 2009. Link

In vitro and in vivo study of aspalathin, a dihydrochalcone component of green rooibos (Aspalathus linearis), in type 2 diabetic db/db mice. Aspalathin dose-dependently increased glucose uptake in L6 myotubes (1–100 μM) and stimulated insulin secretion from RIN-5F pancreatic beta-cells (100 μM). Dietary aspalathin (0.1–0.2%) suppressed the rise in fasting blood glucose of db/db mice over five weeks and improved glucose tolerance.

[1836] Joubert E, de Beer D. Rooibos (Aspalathus linearis) beyond the farm gate — from herbal tea to potential phytopharmaceutical. S Afr J Bot 2011;77(4):869–886. . 2011. Link

Review of rooibos (Aspalathus linearis), an endemic South African fynbos species, tracing its path from traditional herbal tea to potential phytopharmaceutical. The authors summarize cultivation, processing (fermented vs. green rooibos), trade, and the health-promoting properties — most notably antioxidant activity — linked to its bioactive polyphenols including aspalathin. Its caffeine-free, low-tannin status contributes to the tea's popularity.

[1837] Sinisalo M et al. Rooibos tea — case of hepatotoxic reaction. Phytother Res 2010. . 2010.

Case report of a hepatotoxic reaction associated with rooibos tea.

[1838] McKay DL, Blumberg JB. Roles for epigallocatechin gallate and rooibos in chronic disease prevention. Phytother Res 2007. . 2007.

Review on the roles of epigallocatechin gallate and rooibos in chronic disease prevention.

[1839] Loomis D et al. (IARC Monograph WG). Carcinogenicity of drinking coffee, mate, and very hot beverages. Lancet Oncol 2016;17(7):877–878. . 2016. Link

Summary evaluation by the IARC Monographs Working Group (Volume 116) on the carcinogenicity of coffee, mate, and very hot beverages, based on 23 experts reviewing over 1000 human and animal studies. Coffee drinking was found to have inadequate evidence of carcinogenicity (Group 3), with reduced risks suggested for some cancers (liver, endometrium). Drinking very hot beverages (above ~65 °C) was classified as probably carcinogenic (Group 2A) in relation to oesophageal cancer risk.

[1840] Boaventura BC et al. Association of mate tea (Ilex paraguariensis) intake and dyslipidemia in adults — a randomized clinical trial. Nutrition 2012;28(6):657–664. . 2012. Link

OBJECTIVE: To evaluate the effect of long-term ingestion of mate tea, with or without dietary intervention, on the markers of oxidative stress in dyslipidemic individuals. METHODS: Seventy-four dyslipidemic volunteers participated in this randomized clinical trial. Subjects were divided into three treatment groups: mate tea (MT), dietary intervention (DI), and mate tea with dietary intervention (MD). Biochemical and dietary variables were assessed at the beginning of the study (baseline) and after 20, 40, 60, and 90 d of treatment. Participants in the MT and MD groups consumed 1 L/d of mate tea. Those in the DI and MD groups were instructed to increase their intake of fruit, legumes and vegetables and decrease their consumption of foods rich in cholesterol and saturated and trans-fatty acids.

[1841] Heck CI, de Mejia EG. Yerba mate tea (Ilex paraguariensis): a comprehensive review on chemistry, health implications, and technological considerations. J Food Sci 2007;72(9):R138–R151. . 2007. Link

Yerba Mate tea, an infusion made from the leaves of the tree Ilex paraguariensis, is a widely consumed nonalcoholic beverage in South America which is gaining rapid introduction into the world market, either as tea itself or as ingredient in formulated foods or dietary supplements. The indigenous people have used it for centuries as a social and medicinal beverage. Yerba Mate has been shown to be hypocholesterolemic, hepatoprotective, central nervous system stimulant, diuretic, and to benefit the cardiovascular system. It has also been suggested for obesity management. Yerba Mate protects DNA from oxidation and in vitro low-density lipoprotein lipoperoxidation and has a high antioxidant capacity. It has also been reported that Yerba Mate tea is associated to both the prevention and the cause of some types of cancers.

[1842] Klika KD et al. Mate as functional food — meta-analysis. Nutrients 2017;9(7):690. . 2017.

Meta-analysis on mate as a functional food.

[1843] Bracesco N et al. Recent advances on Ilex paraguariensis research: minireview. J Ethnopharmacol 2011;136(3):378–384. . 2011. Link

Minireview (J Ethnopharmacol) on recent advances in Ilex paraguariensis research.

[1844] Loria D et al. Risk of esophageal cancer associated with mate consumption — Argentina meta-analysis. Cancer Epidemiol Biomarkers Prev 2009;18(2):432–438. . 2009. Link

Meta-analysis (Cancer Epidemiol Biomarkers Prev) on the risk of esophageal cancer associated with mate consumption, based on Argentina data.

[1845] de Mejia EG et al. Bioactive components of tea, coffee, and yerba mate. Food Funct 2015;6(2):360–371. . 2015.

Review of the bioactive components of tea, coffee, and yerba mate.

[1846] EFSA Panel on Dietetic Products. Scientific opinion on the safety of caffeine. EFSA J 2015;13(5):4102. . 2015. Link

Scientific opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the safety of caffeine, at the request of the European Commission. The Panel concluded that single doses of caffeine up to 200 mg (about 3 mg/kg bw) raise no safety concern for healthy adults, and that habitual intake up to 400 mg/day does not raise safety concerns for non-pregnant adults. Lower limits (200 mg/day) were advised for pregnant and lactating women.

[1847] Cherbut C et al. Inulin and oligofructose in the dietary fibre concept. Br J Nutr 2002;87(Suppl 2):S159–S162. . 2002. Link

[1848] Kolida S, Gibson GR. Prebiotic capacity of inulin-type fructans. J Nutr 2007;137(11):2503S–2506S. . 2007. Link

The human gut microbiota plays a significant role in human health through its ability to digest food ingredients and manufacture metabolites. This can be positive or negative for host welfare. Moreover, the microflora plays an active role in host defense whereby colonization resistance affords protection against pathogens. Prebiotics are nondigestible food ingredients that target beneficial components of the gut microflora (mainly colonic), particularly the bifidobacteria. In vitro and in vivo evidence has accumulated to confirm the prebiotic effects of inulin-derived fructans.

[1849] EMA/HMPC. Assessment report on Cichorium intybus L., radix. European Medicines Agency 2013. . 2013. Link

EMA/HMPC assessment report on chicory root (Cichorium intybus L., radix).

[1850] Pool-Zobel BL. Inulin-type fructans and reduction in colon cancer risk — review. Br J Nutr 2005;93(Suppl 1):S73–S90. . 2005. Link

Inulin-type fructans (beta(2,1)fructans) extracted from chicory roots (Cichorium intybus) are prebiotic food ingredients, which in the gut lumen are fermented to lactic acid and SCFA. Research in experimental animal models revealed that inulin-type fructans have anticarcinogenic properties. A number of studies report the effects of inulin-type fructans on chemically induced pre-neoplastic lesions (ACF) or tumours in the colon of rats and mice. In twelve studies, there were twenty-nine individual treatment groups of which twenty-four measured aberrant crypt foci (ACF) and five measured tumours. There was a significant reduction of ACF in twenty-one of the twenty-four treatment groups and of tumour incidence in five of the five treatment groups. Higher beneficial effects were achieved by synbiotics (mixtures of probiotics and prebiotics), long-chain inulin-type fructans compared to short-chain derivatives, and feeding high-fat Western style diets.

[1851] Roberfroid MB. Prebiotics: the concept revisited. J Nutr 2007;137(3 Suppl 2):830S–837S. . 2007. Link

[1852] Street RA et al. Cichorium intybus — traditional uses, phytochemistry, pharmacology. Evid Based Complement Alternat Med 2013;2013:579319. . 2013. Link

The genus Cichorium (Asteraceae) is made up of six species with major geographical presence in Europe and Asia. Cichorium intybus, commonly known as chicory, is well known as a coffee substitute but is also widely used medicinally to treat various ailments ranging from wounds to diabetes. Although this plant has a rich history of use in folklore, many of its constituents have not been explored for their pharmacological potential. Toxicological data on C. intybus is currently limited. This review focuses on the economic and culturally important medicinal uses of C. intybus. Traditional uses, scientific validation, and phytochemical composition are discussed in detail.

[1853] EFSA NDA Panel. Scientific opinion on the substantiation of a health claim related to native chicory inulin and maintenance of normal defecation by increasing stool frequency2015;13(1):3951. EFSA Journal. Link

Scientific opinion of the EFSA NDA Panel on the substantiation of a health claim for native chicory inulin and maintenance of normal defecation by increasing stool frequency, under Article 13.5 of Regulation (EC) No 1924/2006. Based on six studies in 86 subjects, the Panel established a cause-and-effect relationship: consuming at least 12 g/day of native chicory inulin increases stool frequency, and this amount is required to obtain the claimed effect.

[1854] Liber A, Szajdek A. Cichorium intybus — chemistry, health effects, food applications. Food Rev Int 2013;29(3):277–293. . 2013.

Review on the chemistry, health effects, and food applications of Cichorium intybus.

[1855] Christensen R, Bartels EM, Altman RD, et al. (2008). Does the hip powder of Rosa canina (rosehip) reduce pain in osteoarthritis patients? — a meta-analysis of randomized controlled trials, 16(9):965-972. Osteoarthritis and Cartilage. 2008. Link

OBJECTIVE: Meta-analysis of randomized controlled trials (RCTs)--of a hip powder of Rosa canina (rosehip) preparation for symptomatic treatment of osteoarthritis (OA), in order to estimate the empirical efficacy as a pain reducing compound. METHOD: RCTs from systematic searches were included if they explicitly stated that OA patients were randomized to either rosehip or placebo. The primary outcome was reduction in pain calculated as effect size (ES), defined as the standardized mean difference (SMD). As secondary analysis the number of responders to therapy was analyzed as Odds Ratios (OR), and expressed as the Number Needed to Treat (NNT). Restricted Maximum Likelihood (REML) methods were applied for the meta-analyses using mixed effects models. RESULTS: The three studies (287 patients and a median trial-duration of 3 months)--all supported by the manufacturer (Hyben-Vital International)--showed a reduction in pain scores by rosehip powder (145 patients) compared to placebo (142 patients): ES of 0.37 [95\% confidence interval (CI): 0.13-0.60], P=0.002.

[1856] Winther K, Apel K, Thamsborg G (2005). A powder made from seeds and shells of a rose-hip subspecies (Rosa canina) reduces symptoms of knee and hip osteoarthritis, 34(4):302-308. Scandinavian Journal of Rheumatology. 2005. Link

OBJECTIVE: The aim of this study was to determine whether a herbal remedy made from a subspecies of rose-hip (Rosa canina) might reduce symptoms of osteoarthritis and consumption of rescue medication in patients suffering from osteoarthritis. METHODS: Ninety-four patients with osteoarthritis of the hip or knee were enrolled in a randomized, placebo-controlled, double-blind crossover trial. Forty-seven patients were given 5 g of the herbal remedy daily for a period of 3 months and the remaining patients were given a similar amount of placebo. The group initially treated with placebo was then changed to rose-hip and vice versa for another 3-month period. Upon inclusion and after 3 weeks and 3 months of each treatment period, pain, stiffness, disability, and global severity of the disease were scored on a Western Ontario and McMaster Universities (WOMAC) questionnaire. After 3 weeks of treatment, patients, if possible, were allowed to reduce their consumption of 'rescue medication'.

[1857] Daels-Rakotoarison DA, Gressier B, Trotin F, et al. (2002). Effects of Rosa canina fruit extract on neutrophil respiratory burst, 16(2):157-161. Phytotherapy Research. 2002. Link

Respiratory burst leads polymorphonuclear neutrophils (PMN) to produce reactive oxygen species (ROS) such as superoxide anions (O(2)(o-)), hypochlorous acid (HOCl) and hydrogen peroxide (H(2)O(2)) which may possess deleterious effects for the organism. Rosa canina fruits are well known to contain a large amount of vitamin C which is antioxidant. This study was focused on the polyphenolics contained in rose hips to evaluate their antioxidative properties. We prepared a rose hip extract deprived of vitamin C. The extract contained mainly phenolics such as proanthocyanidins and flavonoids. We investigated its effects directly against (O(2)(o-)), HOCl and H(2)O(2) and investigated its effects on isolated PMN.

[1858] Mármol I, Sánchez-de-Diego C, Jiménez-Moreno N, et al. (2017). Therapeutic applications of rose hips from different Rosa species, 18(6):1137. International Journal of Molecular Sciences. 2017. Link

Rosa species, rose hips, are widespread wild plants that have been traditionally used as medicinal compounds for the treatment of a wide variety of diseases. The therapeutic potential of these plants is based on its antioxidant effects caused by or associated with its phytochemical composition, which includes ascorbic acid, phenolic compounds and healthy fatty acids among others. Over the last few years, medicinal interest in rose hips has increased as a consequence of recent research that has studied its potential application as a treatment for several diseases including skin disorders, hepatotoxicity, renal disturbances, diarrhoea, inflammatory disorders, arthritis, diabetes, hyperlipidaemia, obesity and cancer. In this review, the role of different species of Rosa in the prevention of treatment of various disorders related to oxidative stress, is examined, focusing on new therapeutic approaches from a molecular point of view.

[1859] Shoba G, Joy D, Joseph T, et al. (1998). Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers, 64(4):353-356. Planta Medica. 1998. Link

The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154\%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low.

[1860] Daily JW, Yang M, Park S (2016). Efficacy of turmeric extracts and curcumin for alleviating the symptoms of joint arthritis: a systematic review and meta-analysis of randomized clinical trials, 19(8):717-729. Journal of Medicinal Food. 2016. Link

Although turmeric and its curcumin-enriched extracts have been used for treating arthritis, no systematic review and meta-analysis of randomized clinical trials (RCTs) have been conducted to evaluate the strength of the research. We systemically evaluated all RCTs of turmeric extracts and curcumin for treating arthritis symptoms to elucidate the efficacy of curcuma for alleviating the symptoms of arthritis. Literature searches were conducted using 12 electronic databases, including PubMed, Embase, Cochrane Library, Korean databases, Chinese medical databases, and Indian scientific database. Search terms used were "turmeric," "curcuma," "curcumin," "arthritis," and "osteoarthritis." A pain visual analogue score (PVAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used for the major outcomes of arthritis. Initial searches yielded 29 articles, of which 8 met specific selection criteria. Three among the included RCTs reported reduction of PVAS (mean difference: -2.04 [-2.85, -1.24]) with turmeric/curcumin in comparison with placebo (P < .00001), whereas meta-analysis of four studies showed a decrease of WOMAC with turmeric/curcumin treatment (mean difference: -15.36 [-26.9, -3.77]; P = .009).

[1861] Lopresti AL, Maes M, Maker GL, et al. (2014). Curcumin for the treatment of major depression: a randomised, double-blind, placebo controlled study , 167:368-375. Journal of Affective Disorders. 2014. Link

Randomised, double-blind, placebo-controlled study comparing curcumin (500 mg twice daily) with placebo over 8 weeks in 56 patients with major depressive disorder; the primary outcome was the IDS-SR30 self-rated depression scale. Both groups improved from baseline to week 4, but from weeks 4 to 8 curcumin was significantly more effective than placebo in improving the IDS-SR30 total and mood scores. Greater efficacy was seen in the subgroup with atypical depression.

[1862] Hewlings SJ, Kalman DS (2017). Curcumin: a review of its effects on human health, 6(10):92. Foods. 2017. Link

Turmeric, a spice that has long been recognized for its medicinal properties, has received interest from both the medical/scientific world and from culinary enthusiasts, as it is the major source of the polyphenol curcumin. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. It may also help in the management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and performance in active people. In addition, a relatively low dose of the complex can provide health benefits for people that do not have diagnosed health conditions. Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects. Ingesting curcumin by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination.

[1864] Safarinejad MR (2005). Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study, 5(4):1-11. Journal of Herbal Pharmacotherapy. 2005. Link

PURPOSE: To determine the effects of therapy with Urtica dioica for symptomatic relief of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: A 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial of Urtica dioica with placebo in 620 patients was conducted. Patients were evaluated using the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), Serum Prostatic- Specific Antigen (PSA), testosterone levels, and prostate size. At the end of 6-month trial, unblinding revealed that patients who initially received the placebo were switched to Urtica dioica. Both groups continued the medication up to 18 months. RESULTS: 558 patients (90\%) completed the study (287/305, 91\% in the Urtica dioica group, and 271/315, 86\% in the placebo group).

[1865] Lopatkin N, Sivkov A, Walther C, et al. (2005). Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms — a placebo-controlled, double-blind, multicenter trial, 23(2):139-146. World Journal of Urology. 2005. Link

The efficacy and tolerability of a fixed combination of 160 mg sabal fruit extract WS 1473 and 120 mg urtica root extract WS 1031 per capsule (PRO 160/120) was investigated in elderly, male patients suffering from lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia in a prospective multicenter trial. A total of 257 patients (129 and 128, respectively) were randomized to treatment with PRO 160/120 or placebo (127 and 126 were evaluable for efficacy). Following a single-blind placebo run-in phase of 2 weeks, the patients received 2 x 1 capsule/day of the study medication under double-blind conditions over a period of 24 weeks. Double-blind treatment was followed by an open control period of 24 weeks during which all patients were administered PRO 160/120. Outcome measures for treatment efficacy included the assessment of the patients' LUTS by means of the I-PSS self-rating questionnaire and a quality of life index as well as uroflow and sonographic parameters. Using the International Prostate Symptom Score (I-PSS), patients treated with PRO 160/120 exhibited a substantially higher total score reduction after 24 weeks of double-blind treatment than patients of the placebo group (6 points vs 4 points; P=0.003, one tailed) with a tendency in the same direction after 16 weeks.

[1866] Roschek B Jr, Fink RC, McMichael M, Alberte RS (2009). Nettle extract (Urtica dioica) affects key receptors and enzymes associated with allergic rhinitis, 23(7):920-926. Phytotherapy Research. 2009. Link

A nettle (Urtica dioica) extract shows in vitro inhibition of several key inflammatory events that cause the symptoms of seasonal allergies. These include the antagonist and negative agonist activity against the Histamine-1 (H(1)) receptor and the inhibition of mast cell tryptase preventing degranulation and release of a host of pro-inflammatory mediators that cause the symptoms of hay fevers. The nettle extract also inhibits prostaglandin formation through inhibition of Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), and Hematopoietic Prostaglandin D(2) synthase (HPGDS), central enzymes in pro-inflammatory pathways. The IC(50) value for histamine receptor antagonist activity was 251 (+/-13) microg mL(-1) and for the histamine receptor negative agonist activity was 193 (+/-71) microg mL(-1). The IC(50) values for inhibition of mast cell tryptase was 172 (+/-28) microg mL(-1), for COX-1 was 160 (+/-47) microg mL(-1), for COX-2 was 275 (+/-9) microg mL(-1), and for HPGDS was 295 (+/-51) microg mL(-1). Through the use of DART TOF-MS, which yields exact masses and relative abundances of compounds present in complex mixtures, bioactives have been identified in nettle that contribute to the inhibition of pro-inflammatory pathways related to allergic rhinitis.

[1867] Chrubasik JE, Roufogalis BD, Wagner H, Chrubasik SA (2007). A comprehensive review on the stinging nettle effect and efficacy profiles, 14(7-8):568-579. Phytomedicine. 2007. Link

Nettle root is recommended for complaints associated with benign prostatic hyperplasia (BPH). We therefore conducted a comprehensive review of the literature to summarise the pharmacological and clinical effects of this plant material. Only a few components of the active principle have been identified and the mechanism of action is still unclear. It seems likely that sex hormone binding globulin (SHBG), aromatase, epidermal growth factor and prostate steroid membrane receptors are involved in the anti-prostatic effect, but less likely that 5alpha-reductase or androgen receptors are involved. Extract and a polysaccharide fraction were shown to exert anti-inflammatory activity. A proprietary methanolic nettle root extract and particular fractions inhibited cell proliferation.

[1868] Jayabalan R et al. A review on kombucha tea: microbiology, composition, fermentation, beneficial effects, toxicity, and tea fungus2014;13(4):538–550. Compr Rev Food Sci Food Saf. Link

Fermentation of sugared tea with a symbiotic culture of acetic acid bacteria and yeast (tea fungus) yields kombucha tea which is consumed worldwide for its refreshing and beneficial properties on human health. Important progress has been made in the past decade concerning research findings on kombucha tea and reports claiming that drinking kombucha can prevent various types of cancer and cardiovascular diseases, promote liver functions, and stimulate the immune system. Considering the widespread reports on kombucha, we recognized the need to review and update the research conducted in relation to kombucha tea, its products and tea fungus. Existing reports have suggested that the protective effects of kombucha tea are as good as those of black tea, however, more studies on kombucha tea and its composition are needed before final conclusions can be made.

[1869] Greenwalt CJ et al. Kombucha, the fermented tea: microbiology, composition, and claimed health effects2000;63(7):976–981. J Food Prot. Link

Kombucha is a slightly sweet, slightly acidic tea beverage consumed worldwide, but historically in China, Russia, and Germany. Kombucha is prepared by fermenting sweetened black tea preparations with a symbiotic culture of yeasts and bacteria. Potential health effects have created an increased interest in Kombucha. Yet, only a few research studies have shown that Kombucha has in vitro antimicrobial activity and enhances sleep and pain thresholds in rats. Furthermore, Kombucha consumption has proven to be harmful in several documented instances.

[1870] Mendelson C et al. Kombucha tea and health: a critical review 2017. Crit Rev Food Sci Nutr. 2017.

Critical review on kombucha tea and health.

[1871] CDC. Unexplained severe illness possibly associated with consumption of Kombucha tea1995;44(48):892–893. MMWR. Link

CDC (MMWR) report on unexplained severe illness possibly associated with kombucha tea consumption.

[1872] Villarreal-Soto SA et al. Understanding kombucha tea fermentation: a review2018;83(3):580–588. J Food Sci. Link

UNLABELLED: Kombucha is a beverage of probable Manchurian origins obtained from fermented tea by a microbial consortium composed of several bacteria and yeasts. This mixed consortium forms a powerful symbiosis capable of inhibiting the growth of potentially contaminating bacteria. The fermentation process also leads to the formation of a polymeric cellulose pellicle due to the activity of certain strains of Acetobacter sp. The tea fermentation process by the microbial consortium was able to show an increase in certain biological activities which have been already studied; however, little information is available on the characterization of its active components and their evolution during fermentation. Studies have also reported that the use of infusions from other plants may be a promising alternative. PRACTICAL APPLICATION: Kombucha is a traditional fermented tea whose consumption has increased in the recent years due to its multiple functional properties such as anti-inflammatory potential and antioxidant activity.

[1874] Kapp JM, Sumner W. Kombucha: a systematic review of the empirical evidence of human health benefit2019;30:66–70. Ann Epidemiol. Link

PURPOSE: Kombucha tea, a fermented beverage, has recently become popular in the United States as part of the functional food movement. This popularity is likely driven by its touted health benefits, coupled with the recent scientific movement investigating the role of the microbiome on human health. The purpose of this systematic review is to describe the literature related to empirical health benefits of kombucha as identified from human subjects research. METHODS: In July 2018, we searched the term "kombucha" for all document types in the following databases across all available years: PubMed, Scopus, and Ovid. To identify federal research grants related to kombucha, we searched the National Institutes of Health Research Portfolio Online Reporting Tools. Finally, to identify ongoing human subjects research, we searched clinicaltrials.gov and clinicaltrialsregister.eu.

[1875] FDA. Acid foods and acidified foods regulations (CFR 21 Part 114). Link

FDA regulation on acid foods and acidified foods (21 CFR Part 114).

[1876] Monash University. Kombucha — Low FODMAP serving guidelines. Link

Monash University Low FODMAP serving guidelines for kombucha.

[1877] Beauchamp GK et al. Phytochemistry: ibuprofen-like activity in extra-virgin olive oil2005;437(7055):45–46. Nature. Link

Newly pressed extra-virgin olive oil contains oleocanthal--a compound whose pungency induces a strong stinging sensation in the throat, not unlike that caused by solutions of the non-steroidal anti-inflammatory drug ibuprofen. We show here that this similar perception seems to be an indicator of a shared pharmacological activity, with oleocanthal acting as a natural anti-inflammatory compound that has a potency and profile strikingly similar to that of ibuprofen. Although structurally dissimilar, both these molecules inhibit the same cyclooxygenase enzymes in the prostaglandin-biosynthesis pathway.

[1878] EFSA. Olive oil polyphenols health claim (CFR 432/2012/EU)2011. EFSA Journal. 2012. Link

Scientific opinion of the EFSA NDA Panel on the substantiation of health claims for olive polyphenols, including protection of LDL particles from oxidative damage. The Panel established a cause-and-effect relationship between consumption of hydroxytyrosol and related compounds from olives and olive oil and protection of blood lipids from oxidative damage. To obtain the effect, at least 5 mg/day of hydroxytyrosol and its derivatives was considered necessary.

[1879] Estruch R et al. PREDIMED trial — primary prevention of cardiovascular disease with a Mediterranean diet supplemented with EVOO2018;378(25):e34. N Engl J Med. Link

BACKGROUND: Observational cohort studies and a secondary prevention trial have shown inverse associations between adherence to the Mediterranean diet and cardiovascular risk. METHODS: In a multicenter trial in Spain, we assigned 7447 participants (55 to 80 years of age, 57\% women) who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was a major cardiovascular event (myocardial infarction, stroke, or death from cardiovascular causes). After a median follow-up of 4.8 years, the trial was stopped on the basis of a prespecified interim analysis. In 2013, we reported the results for the primary end point in the Journal.

[1880] Carnevale R et al. Acute extra-virgin olive oil intake reduces postprandial glycemic and lipidemic increase in T2DM2017. Nutr Metab Cardiovasc Dis. Link

BACKGROUND \& AIMS: Extra virgin olive oil (EVOO) improves post-prandial glycaemia in healthy subjects but it has never been investigated if this can be detected in pre-diabetic patients. We investigated if EVOO affects post-prandial glucose and lipid profile in patients with impaired fasting glucose (IFG). METHODS: Thirty IFG patients were randomly allocated to a meal containing or not 10 g of EVOO in a cross-over design. Before, 60 min and 120 min after lunch a blood sample was taken to measure glucose, insulin, Glucagon-like peptide-1 (GLP1), dipeptidyl-peptidase-4 (DPP4) activity, triglycerides (TG), total cholesterol, HDL-cholesterol and Apo B-48. RESULTS: The meal containing EVOO was associated with a reduction of glucose (p = 0.009) and DPP4 activity (p < 0.001) and a significant increase of insulin (p < 0.001) and GLP-1 (p < 0.001) compared with the meal without EVOO. Furthermore, the meal containing EVOO showed a significant decrease of triglycerides (p = 0.002) and Apo B-48 (p = 0.002) compared with the meal without EVOO.

[1881] Marcelino G et al. Effects of olive oil on gut microbiota: review2019;6:127. Front Nutr. Link

Olive oil is one of the main ingredients in the Mediterranean diet, being an important ally in disease prevention. Its nutritional composition is comprised of mainly monounsaturated fatty acids, with oleic being the major acid, plus minor components which act as effective antioxidants, such as hydroxytyrosol. Studies have shown that the consumption of olive oil, as well as its isolated components or in synergism, can be a primary and secondary protective factor against the development of cardiovascular diseases since it reduces the concentrations of low-density lipoproteins and increases the concentration of high-density lipoproteins. Furthermore, it exerts an influence on the inflammatory markers, such as interleukin-6 and tumor necrosis factor, which are pro-inflammatory agents in the body. The components present in olive oil are also associated with the promotion of intestinal health since they stimulate a higher biodiversity of beneficial gut bacteria, enhancing their balance. The objective of this review is to present recent data on investigated effects of olive oil and its components on the metabolism, focused on cardiovascular diseases, inflammation, and gut biota.

[1882] Owen RW et al. Olives and olive oil in cancer prevention 2004. Eur J Cancer Prev. 2004.

Study on olives and olive oil in cancer prevention.

[1883] Tresserra-Rimbau A et al. Polyphenols and CVD prevention — PREDIMED 2015. Mol Nutr Food Res. 2015.

Study within the PREDIMED trial on polyphenols and cardiovascular disease (CVD) prevention.

[1884] Frankel EN. Chemistry of extra-virgin olive oil — adulteration and detection 2012. Trends Food Sci Technol. 2012.

Review on the chemistry of extra-virgin olive oil, adulteration, and its detection.

[1885] de Souza RJ et al. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. BMJ 2015;351:h3978. . 2015. Link

OBJECTIVE: To systematically review associations between intake of saturated fat and trans unsaturated fat and all cause mortality, cardiovascular disease (CVD) and associated mortality, coronary heart disease (CHD) and associated mortality, ischemic stroke, and type 2 diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane Central Registry of Controlled Trials, Evidence-Based Medicine Reviews, and CINAHL from inception to 1 May 2015, supplemented by bibliographies of retrieved articles and previous reviews. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies reporting associations of saturated fat and/or trans unsaturated fat (total, industrially manufactured, or from ruminant animals) with all cause mortality, CHD/CVD mortality, total CHD, ischemic stroke, or type 2 diabetes. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed study risks of bias. Multivariable relative risks were pooled.

[1886] Dehghan M et al. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study. Lancet 2017;390(10107):2050–2062. . 2017. Link

BACKGROUND: The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear. METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a large, epidemiological cohort study of individuals aged 35-70 years (enrolled between Jan 1, 2003, and March 31, 2013) in 18 countries with a median follow-up of 7·4 years (IQR 5·3-9·3). Dietary intake of 135 335 individuals was recorded using validated food frequency questionnaires. The primary outcomes were total mortality and major cardiovascular events (fatal cardiovascular disease, non-fatal myocardial infarction, stroke, and heart failure). Secondary outcomes were all myocardial infarctions, stroke, cardiovascular disease mortality, and non-cardiovascular disease mortality.

[1887] Astrup A et al. Saturated fats and health: a reassessment and proposal for food-based recommendations. Am J Clin Nutr 2020;112(5):1080–1082. . 2020. Link

Opinion reassessing saturated fats and health, with a proposal for food-based recommendations.

[1888] Brassard D et al. Comparison of the impact of SFAs from cheese and butter on cardiometabolic risk factors: a randomized controlled trial. Am J Clin Nutr 2017;105(4):800–809. . 2017. Link

Background: Controversies persist concerning the association between intake of dietary saturated fatty acids (SFAs) and cardiovascular disease risk.Objective: We compared the impact of consuming equal amounts of SFAs from cheese and butter on cardiometabolic risk factors.Design: In a multicenter, crossover, randomized controlled trial, 92 men and women with abdominal obesity and relatively low HDL-cholesterol concentrations were assigned to sequences of 5 predetermined isoenergetic diets of 4 wk each separated by 4-wk washouts: 2 diets rich in SFAs (12.4-12.6\% of calories) from either cheese or butter; a monounsaturated fatty acid (MUFA)-rich diet (SFAs: 5.8\%, MUFAs: 19.6\%); a polyunsaturated fatty acid (PUFA)-rich diet (SFAs: 5.8\%, PUFAs: 11.5\%); and a low-fat, high-carbohydrate diet (fat: 25\%, SFAs: 5.8\%).Results: Serum HDL-cholesterol concentrations were similar after the cheese and butter diets but were significantly higher than after the carbohydrate diet (+3.8\% and +4.7\%, respectively; P < 0.05 for both). LDL-cholesterol concentrations after the cheese diet were lower than after the butter diet (-3.3\%, P < 0.05) but were higher than after the carbohydrate (+2.6\%), MUFA (+5.3\%), and PUFA (+12.3\%) diets (P < 0.05 for all). LDL-cholesterol concentrations after the butter diet also increased significantly (from +6.1\% to +16.2\%, P < 0.05) compared with the carbohydrate, MUFA, and PUFA diets. The LDL-cholesterol response to treatment was significantly modified by baseline values (P-interaction = 0.02), with the increase in LDL cholesterol being significantly greater with butter than with cheese only among individuals with high baseline LDL-cholesterol concentrations. There was no significant difference between all diets on inflammation markers, blood pressure, and insulin-glucose homeostasis.Conclusions: The results of our study suggest that the consumption of SFAs from cheese and butter has similar effects on HDL cholesterol but differentially modifies LDL-cholesterol concentrations compared with the effects of carbohydrates, MUFAs, and PUFAs, particularly in individuals with high LDL cholesterol. In contrast, SFAs from either cheese or butter have no significant effects on several other nonlipid cardiometabolic risk factors.

[1889] Timby N et al. Neurodevelopment, nutrition, and growth until 12 mo of age in infants fed a low-energy, low-protein formula supplemented with bovine milk fat globule membranes: a randomized controlled trial. Am J Clin Nutr 2014;99(4):860–868. . 2014. Link

BACKGROUND: Observational studies have indicated that differences in the composition of human milk and infant formula yield benefits in cognitive development and early growth for breastfed infants. OBJECTIVE: The objective was to test the hypothesis that feeding an infant formula with reduced energy and protein densities and supplemented with bovine milk fat globule membrane (MFGM) reduces differences in cognitive development and early growth between formula-fed and breastfed infants. DESIGN: In a prospective, double-blind, randomized controlled trial, 160 infants <2 mo of age were randomly assigned to be fed an MFGM-supplemented, low-energy, low-protein experimental formula (EF) or a standard formula (SF) until 6 mo of age. The energy and protein contents of the EF and SF were 60 and 66 kcal/100 mL and 1.20 and 1.27 g/100 mL, respectively. A breastfed reference (BFR) group consisted of 80 infants. RESULTS: At 12 mo of age, the cognitive score (mean ± SD) on testing with the Bayley Scales of Infant and Toddler Development, Third Edition, was significantly higher in the EF group than in the SF group (105.8 ± 9.2 compared with 101.8 ± 8.0; P = 0.008) but was not significantly different from that in the BFR group (106.4 ± 9.5; P = 0.73).

[1890] EFSA Panel. Scientific Opinion on Dietary Reference Values for fats. EFSA Journal 2010;8(3):1461. . 2010. Link

EFSA Panel scientific opinion on Dietary Reference Values for fats.

[1891] ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J 2020;41(1):111–188. . 2020. Link

ESC/EAS Guidelines for the management of dyslipidaemias.

[1892] FDA. Final Determination Regarding Partially Hydrogenated Oils. Federal Register 2015;80(116):34650–34670. . 2015. Link

FDA Final Determination regarding partially hydrogenated oils.

[1893] Sharma H et al. Effect of dietary clarified butter on serum lipid profile and immune response in healthy adults. J Ayurveda Integr Med 2010;1(2):141–146. . 2010. Link

Ghee, also known as clarified butter, has been utilized for thousands of years in Ayurveda as a therapeutic agent. In ancient India, ghee was the preferred cooking oil. In the last several decades, ghee has been implicated in the increased prevalence of coronary artery disease (CAD) in Asian Indians due to its content of saturated fatty acids and cholesterol and, in heated ghee, cholesterol oxidation products. Our previous research on Sprague-Dawley outbred rats, which serve as a model for the general population, showed no effect of 5 and 10\% ghee-supplemented diets on serum cholesterol and triglycerides. However, in Fischer inbred rats, which serve as a model for genetic predisposition to diseases, results of our previous research showed an increase in serum total cholesterol and triglyceride levels when fed a 10\% ghee-supplemented diet. In the present study, we investigated the effect of 10\% dietary ghee on microsomal lipid peroxidation, as well as serum lipid levels in Fischer inbred rats to assess the effect of ghee on free radical mediated processes that are implicated in many chronic diseases including cardiovascular disease.

[1894] Singh RB et al. Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): a randomised single-blind trial. Lancet 2002;360(9344):1455–1461. . 2002. Link

BACKGROUND: The rapid emergence of coronary artery disease (CAD) in south Asian people is not explained by conventional risk factors. In view of cardioprotective effects of a Mediterranean style diet rich in alpha-linolenic acid, we assessed the benefits of this diet for patients at high risk of CAD. METHODS: We did a randomised, single-blind trial in 1000 patients with angina pectoris, myocardial infarction, or surrogate risk factors for CAD. 499 patients were allocated to a diet rich in whole grains, fruits, vegetables, walnuts, and almonds. 501 controls consumed a local diet similar to the step I National Cholesterol Education Program (NCEP) prudent diet. FINDINGS: The intervention group consumed more fruits, vegetables, legumes, walnuts, and almonds than did controls (573 g [SD 127] vs 231 g [19] per day p<0.001). The intervention group had an increased intake of whole grains and mustard or soy bean oil. The mean intake of alpha-linolenic acid was two-fold greater in the intervention group (1.8 g [SD 0.4] vs 0.8 g [0.2] per day, p<0.001).

[1895] Joshi K et al. Docosahexaenoic acid content is significantly higher in ghṛta prepared by traditional Ayurvedic method. J Ayurveda Integr Med 2014;5(2):85–88. . 2014. Link

BACKGROUND: Ghee (clarified butter) also known as ghrita, has been utilized for thousands of years in Ayurveda. Ghee is mostly prepared by traditional method in Indian households or by direct cream method at industry level. Ayurvedic classics mention that ghrita made from cow milk is superior. However, there is no scientific comparison available on preparation methods and essential fatty acids content of ghrita. OBJECTIVE: To investigate fatty acid composition of ghrita prepared by traditional/Ayurvedic method and commercial method (direct cream method). MATERIALS AND METHODS: Fatty Acid Methyl Esters (FAME) extracted from ghrita samples were analysed on Gas Chromatography (GC) Shimadzu B using capillary column BPX70 (0.32 mm*60 m, ID of 0.25 mm).

[1896] Astrup A et al. Saturated fats and health: a reassessment. Am J Clin Nutr 2020;112(5):1080–1082. . 2020. Link

Paper reassessing saturated fats and health.

[1897] FSSAI India. Food Safety and Standards (Prohibition and Restrictions on Sales) Regulations — Trans fat limits 2021. . 2021.

FSSAI India regulation on trans fat limits in foods.

[1898] . Charaka Samhita, Sutrasthana 27 (klasszikus ájurvédikus referencia).

Classical Ayurvedic source text: Charaka Samhita, Sutrasthana, chapter 27.

[1900] Mozaffarian D et al. Trans fatty acids and cardiovascular disease. N Engl J Med 2006;354(15):1601–1613. . 2006. Link

Paper on trans fatty acids and cardiovascular disease.

[1901] Burdge GC, Wootton SA. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. Br J Nutr 2002;88(4):411–420. . 2002. Link

The extent to which women of reproductive age are able to convert the n-3 fatty acid alpha-linolenic acid (ALNA) to eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) was investigated in vivo by measuring the concentrations of labelled fatty acids in plasma for 21 d following the ingestion of [U-13C]ALNA (700 mg). [13C]ALNA excursion was greatest in cholesteryl ester (CE) (224 (sem 70) micromol/l over 21 d) compared with triacylglycerol (9-fold), non-esterified fatty acids (37-fold) and phosphatidylcholine (PC, 7-fold). EPA excursion was similar in both PC (42 (sem 8) micromol/l) and CE (42 (sem 9) micromol/l) over 21 d. In contrast both [13C]DPA and [13C]DHA were detected predominately in PC (18 (sem 4) and 27 (sem 7) micromol/l over 21 d, respectively). Estimated net fractional ALNA inter-conversion was EPA 21 \%, DPA 6 \% and DHA 9 \%. Approximately 22 \% of administered [13C]ALNA was recovered as 13CO2 on breath over the first 24 h of the study. These results suggest differential partitioning of ALNA, EPA and DHA between plasma lipid classes, which may facilitate targeting of individual n-3 fatty acids to specific tissues.

[1902] Plourde M, Cunnane SC. Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements. Appl Physiol Nutr Metab 2007;32(4):619–634. . 2007. Link

There is considerable interest in the potential impact of several polyunsaturated fatty acids (PUFAs) in mitigating the significant morbidity and mortality caused by degenerative diseases of the cardiovascular system and brain. Despite this interest, confusion surrounds the extent of conversion in humans of the parent PUFA, linoleic acid or alpha-linolenic acid (ALA), to their respective long-chain PUFA products. As a result, there is uncertainty about the potential benefits of ALA versus eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). Some of the confusion arises because although mammals have the necessary enzymes to make the long-chain PUFA from the parent PUFA, in vivo studies in humans show that asymptotically equal to 5\% of ALA is converted to EPA and <0.5\% of ALA is converted to DHA. Because the capacity of this pathway is very low in healthy, nonvegetarian humans, even large amounts of dietary ALA have a negligible effect on plasma DHA, an effect paralleled in the omega6 PUFA by a negligible effect of dietary linoleic acid on plasma arachidonic acid. Despite this inefficient conversion, there are potential roles in human health for ALA and EPA that could be independent of their metabolism to DHA through the desaturation - chain elongation pathway.

[1903] Khalesi S et al. Flaxseed consumption may reduce blood pressure: a systematic review and meta-analysis of controlled trials. J Nutr 2015;145(4):758–765. . 2015. Link

A systematic review and meta-analysis of controlled trials examining the potential blood-pressure-lowering effect of flaxseed consumption.

[1904] Pan A et al. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr 2009;90(2):288–297. . 2009. Link

BACKGROUND: Several clinical trials have investigated the effects of flaxseed and flaxseed-derived products (flaxseed oil or lignans) on blood lipids; however, the findings have been inconsistent. OBJECTIVE: We aimed to identify and quantify the effectiveness of flaxseed and its derivatives on blood lipid profiles. DESIGN: A comprehensive literature search was performed on the basis of English reports of randomized controlled trials of flaxseed or its derivatives on lipid profiles in adults, which were published from January 1990 to October 2008. Attempts also were made to access unpublished data. Study quality was assessed by using the Jadad score, and a meta-analysis was conducted. RESULTS: Twenty-eight studies were included.

[1905] Rodriguez-Leyva D et al. Potent antihypertensive action of dietary flaxseed in hypertensive patients. Hypertension 2013;62(6):1081–1089. . 2013. Link

Flaxseed contains ω-3 fatty acids, lignans, and fiber that together may provide benefits to patients with cardiovascular disease. Animal work identified that patients with peripheral artery disease may particularly benefit from dietary supplementation with flaxseed. Hypertension is commonly associated with peripheral artery disease. The purpose of the study was to examine the effects of daily ingestion of flaxseed on systolic (SBP) and diastolic blood pressure (DBP) in peripheral artery disease patients. In this prospective, double-blinded, placebo-controlled, randomized trial, patients (110 in total) ingested a variety of foods that contained 30 g of milled flaxseed or placebo each day over 6 months. Plasma levels of the ω-3 fatty acid α-linolenic acid and enterolignans increased 2- to 50-fold in the flaxseed-fed group but did not increase significantly in the placebo group.

[1906] Alpha Omega Trial Group. n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med 2010;363(21):2015–2026. . 2010. Link

BACKGROUND: Results from prospective cohort studies and randomized, controlled trials have provided evidence of a protective effect of n-3 fatty acids against cardiovascular diseases. We examined the effect of the marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and of the plant-derived alpha-linolenic acid (ALA) on the rate of cardiovascular events among patients who have had a myocardial infarction. METHODS: In a multicenter, double-blind, placebo-controlled trial, we randomly assigned 4837 patients, 60 through 80 years of age (78\% men), who had had a myocardial infarction and were receiving state-of-the-art antihypertensive, antithrombotic, and lipid-modifying therapy to receive for 40 months one of four trial margarines: a margarine supplemented with a combination of EPA and DHA (with a targeted additional daily intake of 400 mg of EPA-DHA), a margarine supplemented with ALA (with a targeted additional daily intake of 2 g of ALA), a margarine supplemented with EPA-DHA and ALA, or a placebo margarine. The primary end point was the rate of major cardiovascular events, which comprised fatal and nonfatal cardiovascular events and cardiac interventions. Data were analyzed according to the intention-to-treat principle, with the use of Cox proportional-hazards models. RESULTS: The patients consumed, on average, 18.8 g of margarine per day, which resulted in additional intakes of 226 mg of EPA combined with 150 mg of DHA, 1.9 g of ALA, or both, in the active-treatment groups.

[1907] Caligiuri SP et al. Flaxseed for hypertension: implications for blood pressure regulation. Curr Hypertens Rep 2014;16(12):499. . 2014. Link

A review discussing flaxseed in hypertension and its implications for blood pressure regulation.

[1908] EFSA. Scientific Opinion on dietary reference values for fats, including omega-3 PUFAs. EFSA Journal 2010;8(3):1461. . 2010. Link

An EFSA scientific opinion on dietary reference values for fats, including omega-3 PUFAs.

[1909] Estruch R et al. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med 2018;378(25):e34. . 2018. Link

A report from the PREDIMED randomized trial on a Mediterranean diet supplemented with extra-virgin olive oil or nuts for primary prevention of cardiovascular disease.

[1910] Ros E et al. A walnut diet improves endothelial function in hypercholesterolemic subjects: a randomized crossover trial2004;109(13):1609–1614. Circulation. Link

BACKGROUND: Epidemiological studies suggest that nut intake decreases coronary artery disease (CAD) risk. Nuts have a cholesterol-lowering effect that partly explains this benefit. Endothelial dysfunction is associated with CAD and its risk factors and is reversed by antioxidants and marine n-3 fatty acids. Walnuts are a rich source of both antioxidants and alpha-linolenic acid, a plant n-3 fatty acid. METHODS AND RESULTS: To test the hypothesis that walnut intake will reverse endothelial dysfunction, we randomized in a crossover design 21 hypercholesterolemic men and women to a cholesterol-lowering Mediterranean diet and a diet of similar energy and fat content in which walnuts replaced approximately 32\% of the energy from monounsaturated fat. Participants followed each diet for 4 weeks.

[1911] Andreux PA et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nat Metab 2019;1(6):595–603. . 2019. Link

A human study on the safety of the mitophagy activator urolithin A and its molecular signature of improved mitochondrial and cellular health.

[1912] Tomás-Barberán FA et al. Urolithins, the rescue of 'old' metabolites to understand a 'new' concept: metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis, and host health status. Mol Nutr Food Res 2017;61(1):1500901. . 2017. Link

[1913] Kim SY et al. Walnut polyphenol metabolites, urolithins A and B, inhibit the expression of the proinflammatory cytokine. Mol Nutr Food Res 2018;62(13):e1701123. . 2018.

An experimental study on the walnut polyphenol metabolites urolithins A and B inhibiting proinflammatory cytokine expression.

[1914] Bao Y et al. Association of nut consumption with total and cause-specific mortality. N Engl J Med 2013;369(21):2001–2011. . 2013. Link

BACKGROUND: Increased nut consumption has been associated with a reduced risk of major chronic diseases, including cardiovascular disease and type 2 diabetes mellitus. However, the association between nut consumption and mortality remains unclear. METHODS: We examined the association between nut consumption and subsequent total and cause-specific mortality among 76,464 women in the Nurses' Health Study (1980-2010) and 42,498 men in the Health Professionals Follow-up Study (1986-2010). Participants with a history of cancer, heart disease, or stroke were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. RESULTS: During 3,038,853 person-years of follow-up, 16,200 women and 11,229 men died.

[1915] Banel DK, Hu FB. Effects of walnut consumption on blood lipids and other cardiovascular risk factors: a meta-analysis and systematic review. Am J Clin Nutr 2009;90(1):56–63. . 2009. Link

A meta-analysis and systematic review of the effects of walnut consumption on blood lipids and other cardiovascular risk factors.

[1917] Sacks FM et al. Dietary fats and cardiovascular disease: a presidential advisory from the American Heart Association. Circulation 2017;136(3):e1–e23. . 2017. Link

Cardiovascular disease (CVD) is the leading global cause of death, accounting for 17.3 million deaths per year. Preventive treatment that reduces CVD by even a small percentage can substantially reduce, nationally and globally, the number of people who develop CVD and the costs of caring for them. This American Heart Association presidential advisory on dietary fats and CVD reviews and discusses the scientific evidence, including the most recent studies, on the effects of dietary saturated fat intake and its replacement by other types of fats and carbohydrates on CVD. In summary, randomized controlled trials that lowered intake of dietary saturated fat and replaced it with polyunsaturated vegetable oil reduced CVD by ≈30\%, similar to the reduction achieved by statin treatment. Prospective observational studies in many populations showed that lower intake of saturated fat coupled with higher intake of polyunsaturated and monounsaturated fat is associated with lower rates of CVD and of other major causes of death and all-cause mortality. In contrast, replacement of saturated fat with mostly refined carbohydrates and sugars is not associated with lower rates of CVD and did not reduce CVD in clinical trials.

[1918] Eyres L et al. Coconut oil consumption and cardiovascular risk factors in humans. Nutr Rev 2016;74(4):267–280. . 2016. Link

Coconut oil is being heavily promoted as a healthy oil, with benefits that include support of heart health. To assess the merits of this claim, the literature on the effect of coconut consumption on cardiovascular risk factors and outcomes in humans was reviewed. Twenty-one research papers were identified for inclusion in the review: 8 clinical trials and 13 observational studies. The majority examined the effect of coconut oil or coconut products on serum lipid profiles. Coconut oil generally raised total and low-density lipoprotein cholesterol to a greater extent than cis unsaturated plant oils, but to a lesser extent than butter. The effect of coconut consumption on the ratio of total cholesterol to high-density lipoprotein cholesterol was often not examined.

[1919] Khaw KT et al. Randomised trial of coconut oil, olive oil or butter on blood lipids and other cardiovascular risk factors in healthy men and women. BMJ Open 2018;8(3):e020167. . 2018. Link

INTRODUCTION: High dietary saturated fat intake is associated with higher blood concentrations of low-density lipoprotein cholesterol (LDL-C), an established risk factor for coronary heart disease. However, there is increasing interest in whether various dietary oils or fats with different fatty acid profiles such as extra virgin coconut oil may have different metabolic effects but trials have reported inconsistent results. We aimed to compare changes in blood lipid profile, weight, fat distribution and metabolic markers after four weeks consumption of 50 g daily of one of three different dietary fats, extra virgin coconut oil, butter or extra virgin olive oil, in healthy men and women in the general population. DESIGN: Randomised clinical trial conducted over June and July 2017. SETTING: General community in Cambridgeshire, UK. PARTICIPANTS: Volunteer adults were recruited by the British Broadcasting Corporation through their websites.

[1920] Neelakantan N et al. The effect of coconut oil consumption on cardiovascular risk factors: a systematic review and meta-analysis of clinical trials. Circulation 2020;141(10):803–814. . 2020. Link

A systematic review and meta-analysis of clinical trials on the effect of coconut oil consumption on cardiovascular risk factors.

[1921] Marina AM et al. Antioxidant capacity and phenolic acids of virgin coconut oil. Int J Food Sci Nutr 2009;60(Suppl 2):114–123. . 2009. Link

The antioxidant properties of virgin coconut oil produced through chilling and fermentation were investigated and compared with refined, bleached and deodorized coconut oil. Virgin coconut oil showed better antioxidant capacity than refined, bleached and deodorized coconut oil. The virgin coconut oil produced through the fermentation method had the strongest scavenging effect on 1,1-diphenyl-2-picrylhydrazyl and the highest antioxidant activity based on the beta-carotene-linoleate bleaching method. However, virgin coconut oil obtained through the chilling method had the highest reducing power. The major phenolic acids detected were ferulic acid and p-coumaric acid. Very high correlations were found between the total phenolic content and scavenging activity (r=0.91), and between the total phenolic content and reducing power (r=0.96).

[1922] Lieberman S et al. A review of monolaurin and lauric acid: natural virucidal and bactericidal agents. Altern Complement Ther 2006;12(6):310–314. . 2006. Link

Review of monolaurin and lauric acid as potential natural virucidal and bactericidal agents, framed by the problem of antibiotic resistance. The authors report that monolaurin has substantially greater virucidal and bactericidal activity than lauric acid itself, with in vitro efficacy against lipid-coated viruses and Gram-positive bacteria (e.g., Staphylococcus aureus, Streptococcus pyogenes). Of note, the article is a narrative rather than systematic review.

[1923] Bach AC, Babayan VK. Medium-chain triglycerides: an update. Am J Clin Nutr 1982;36(5):950–962. (klasszikus MCT-definíció). . 1982. Link

A review of the literature on the medical and nutritional use of medium-chain triglycerides (MCTs) since 1970 is presented with additional discussions on the various modifications and applications of the MCTs in the synthesis of certain structured lipids. The metabolism of MCTs in the liver and extrahepatic tissues is discussed along with further documentation of the use of MCTs in malabsorption and hyperlipidemia cases. Recent applications of MCTs and modified MCTs in hyperalimentation, deficiency in the carnitine system, epilepsy, obesity, and other special areas of application are cited. The use of medium-chain monodiglycerides for dissolving cholesterol gallstones is presented. The contraindications for the use of MCTs in ketosis, acidosis, and cirrhosis are also discussed. Suggestions for use of MCTs in a variety of medical and nutritional applications are presented.

[1925] Davis AJ et al. Authentication of extra virgin avocado oil sold in the United States. Food Control 2020;116:107310. . 2020. Link

A study on the authentication of extra virgin avocado oil sold in the United States.

[1926] Carranza-Madrigal J et al. Effects of a vegetarian diet vs. a vegetarian diet enriched with avocado in hypercholesterolemic patients. Arch Med Res 1995;26(3):215–219. . 1995.

A study in hypercholesterolemic patients comparing a vegetarian diet with a vegetarian diet enriched with avocado.

[1927] Unlu NZ et al. Carotenoid absorption from salad and salsa by humans is enhanced by the addition of avocado or avocado oil. J Nutr 2005;135(3):431–436. . 2005. Link

[1928] Schwingshackl L et al. Olive oil in the prevention and management of type 2 diabetes mellitus: a systematic review and meta-analysis of cohort studies and intervention trials. Nutr Diabetes 2018;8:1–9. (analóg MUFA-evidencia). . 2018. Link

BACKGROUND/OBJECTIVES: Olive oil (OO) as food is composed mainly of fatty acids and bioactive compounds depending from the extraction method. Both had been discussed as health promoting with still open questions. Thus, we conducted a meta-analysis to illustrate the impact of this food on type 2 diabetes (T2D) by investigating the association between OO intake and risk of T2D, and the effect of OO intake in the management of T2D. SUBJECTS/METHODS: Searches were performed in PubMed, Cochrane Library and google scholar. First, we conducted a random effect meta-analysis of prospective cohort studies and trials investigating the association between OO and risk of T2D. Second, a meta-analysis was performed to detect the effects of olive oil on glycemic control in patients with T2D.

[1929] Flores M et al. Avocado oil: characteristics, properties and applications. Molecules 2019;24(11):2172. . 2019. Link

A review of the characteristics, properties, and applications of avocado oil.

[1930] Yamassaki FT et al. Avocado oil for cardiovascular prevention: a systematic review. Curr Nutr Rep 2023;12(2):331–342. . 2023.

A systematic review of avocado oil for cardiovascular prevention.

[1931] Brueck H et al. The latex-fruit syndrome and the avocado allergen Pers a 1. Allergy 2000;55(9):779–785. . 2000.

An article on the latex-fruit syndrome and the avocado allergen Pers a 1.

[1933] Hong H, Kim CS, Maeng S Nutr Res Pract. 2009;3(4):323–327. Effects of pumpkin seed oil and saw palmetto oil in Korean men with symptomatic benign prostatic hyperplasia. 2009. Link

This study was to investigate the role of complementary and alternative medicine in the prevention and treatment of benign prostatic hyperplasia. For this purpose, a randomized, double-blind, placebo-controlled trial was performed over 12 months on 47 benign prostatic hyperplasia patients with average age of 53.3 years and international prostate symptom score over 8. Subjects received either sweet potato starch (group A, placebo, 320 mg/day), pumpkin seed oil (group B, 320 mg/day), saw palmetto oil (group C, 320 mg/day) or pumpkin seed oil plus saw palmetto oil (group D, each 320 mg/day). International prostate symptom score, quality of life, serum prostate specific antigen, prostate volume and maximal urinary flow rate were measured. In groups B, C and D, the international prostate symptom score were reduced by 3 months. Quality of life score was improved after 6 months in group D, while those of groups B and C were improved after 3 months, compared to the baseline value.

[1934] Vahlensieck W, et al. Urol Int. 2015;94(3):286–295. Effects of pumpkin seed in men with lower urinary tract symptoms due to benign prostatic hyperplasia: GRANU study. 2015. Link

INTRODUCTION: The German Research Activities on Natural Urologicals (GRANU) study was a randomized, partially blinded, placebo-controlled, parallel-group trial that investigated the efficacy of pumpkin seed in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH/LUTS). SUBJECTS AND METHODS: A total of 1,431 men (50-80 years) with BPH/LUTS were randomly assigned to either pumpkin seed (5 g b.i.d.), capsules with pumpkin seed extract (500 mg b.i.d.) or matching placebo. The primary response criterion was a decrease in International Prostate Symptom Score (IPSS) of ≥5 points from baseline after 12 months. Secondary outcome measures included IPSS-related quality of life, IPSS single items and diary-recorded nocturia. RESULTS: After 12 months, the response rate (intention-to-treat/last-observation-carried-forward approach) did not differ between pumpkin seed extract and placebo. In the case of pumpkin seed (responders: 58.5\%), the difference compared with placebo (responders: 47.3\%) was descriptively significant.

[1935] Gossell-Williams M, et al. Climacteric. 2011;14(5):558–564. Improvement in HDL cholesterol in postmenopausal women supplemented with pumpkin seed oil: pilot study. 2011. Link

A pilot study on the improvement in HDL cholesterol in postmenopausal women supplemented with pumpkin seed oil.

[1936] Berger MM, et al. Pak J Pharm Sci. 2014. Pumpkin seed oil in patients with overactive bladder. 2014.

A study on pumpkin seed oil in patients with overactive bladder.

[1937] Cao R, et al. Phytochem Rev. 2013. Pumpkin seed lignans and their bioactive potential. 2013.

A review of pumpkin seed lignans and their bioactive potential.

[1938] . EU Commission Regulation 1996. Steirisches Kürbiskernöl g.g.A. (PGI) registration. 1996.

An EU Commission Regulation on the registration of Steirisches Kurbiskernol as a Protected Geographical Indication (PGI).

[1939] Glew RH, et al. Ecol Food Nutr. 2006. Amino acid, fatty acid, and mineral composition of Cucurbita pepo seeds. 2006.

A study on the amino acid, fatty acid, and mineral composition of Cucurbita pepo seeds.

[1940] Sankar D, et al. J Med Food. 2006;9(3):408–412. A pilot study of open label sesame oil in hypertensive diabetics. 2006. Link

The objective of this study was to investigate the effect of sesame oil in hypertensive diabetics medicated with atenolol (beta-blocker) and glibenclamide (sulfonylurea). This open label trial with two intervention periods comprised 22 male and 18 female patients, 45-65 years old, with mild to moderate hypertension and diabetes. Sesame oil (Idhayam Gingelly oil, V.V.V. \& Sons, Virudhunagar, Tamilnadu, India) was supplied to the patients, who were instructed to use it in place of other cooking oils for 45 days. Blood pressure (BP), anthropometric measurements, plasma glucose, glycated hemoglobin (HbA1c), lipid profiles [total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol, and triglycerides (TG)], lipid peroxidation [thiobarbituric acid-reactive substances (TBARS)], electrolytes (sodium, potassium, and chloride), and enzymic (superoxide dismutase, glutathione peroxidase, and catalase) and nonenzymic (vitamin C, vitamin E, beta-carotene, and reduced glutathione) antioxidants were measured at baseline and after 45 days of sesame oil substitution. The same patients were then switched over to other oils like palm or groundnut oils as their regular oils at random for another 45 days, and the investigations were carried out again at the end. Systolic and diastolic BP decreased remarkably.

[1941] Devarajan S, et al. J Clin Biochem Nutr. 2016;59(3):219–225. Sesame oil and rice bran oil ameliorate hypertension and improve insulin sensitivity in diabetic and hypertensive subjects. 2016. Link

A study on sesame oil and rice bran oil and their effects on hypertension and insulin sensitivity in diabetic and hypertensive subjects.

[1942] Penumathsa SV, et al. Evid Based Complement Alternat Med. 2009. Sesamin: a naturally occurring lignan inhibits CYP3A4 by antagonizing the pregnane X receptor activation. 2009. Link

A study on sesamin, a naturally occurring lignan that inhibits CYP3A4 by antagonizing pregnane X receptor activation.

[1943] Nakano D, et al. Clin Exp Pharmacol Physiol. 2002;29(11):1014–1015. Lignans from sesame oil and antihypertensive effects. 2002.

An article on lignans from sesame oil and their antihypertensive effects.

[1944] Sirato-Yasumoto S, et al. J Agric Food Chem. 2001;49(5):2647–2651. Effect of sesame seeds rich in sesamin and sesamolin on fatty acid oxidation in rat liver. 2001. Link

Activities of enzymes involved in hepatic fatty acid oxidation and synthesis among rats fed sesame (Sesamum indicum L.) differing in lignan content (sesamin and sesamolin) were compared. Sesame seeds rich in lignans from two lines, 0730 and 0732, lines established in this laborary, and those from a conventional cultivar (Masekin) were employed. Seeds from the 0730 and 0732 lines contained sesamin and sesamolin at amounts twice those from Masekin. Sesame seeds were added at levels of 200 g/kg to the experimental diets. Sesame increased both the hepatic mitochondrial and the peroxisomal fatty acid oxidation rate. Increases were greater with sesame rich in lignans than with Maskin.

[1945] . FDA US Food and Drug Administration. Sesame as the 9th major food allergen (FASTER Act, effective. 2023.

An FDA notice on sesame being designated the 9th major food allergen under the FASTER Act.

[1946] Hsu DZ, et al. Free Radic Biol Med. 2013. Sesamol attenuates LPS-induced acute kidney injury through inhibition of inflammation and oxidative stress. 2013.

An experimental study on sesamol attenuating LPS-induced acute kidney injury through inhibition of inflammation and oxidative stress.

[1947] Callaway J, et al. J Dermatolog Treat. 2005;16(2):87–94. Efficacy of dietary hempseed oil in patients with atopic dermatitis. 2005. Link

BACKGROUND: Hempseed oil is a rich and balanced source of omega-6 and omega-3 polyunsaturated fatty acids (PUFAs). Anecdotal evidence indicated that dietary hempseed oil might be useful in treating symptoms of atopic dermatitis. PATIENTS AND METHODS: Dietary hempseed oil and olive oil were compared in a 20-week randomized, single-blind crossover study with atopic patients. Fatty acid profiles were measured in plasma triglyceride, cholesteryl and phospholipid fractions. A patient questionnaire provided additional information on skin dryness, itchiness and usage of dermal medications. Skin transepidermal water loss (TEWL) was also measured.

[1948] Schwab US, et al. Eur J Clin Nutr. 2006;60(11):1320–1328. Effects of hempseed and flaxseed oils on the profile of serum lipids, serum total and lipoprotein lipid concentrations and haemostatic factors. 2006. Link

BACKGROUND: Both hempseed oil (HO) and flaxseed oil (FO) contain high amounts of essential fatty acids (FAs); i.e. linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3), but almost in opposite ratios. An excessive intake of one essential FA over the other may interfere with the metabolism of the other while the metabolisms of LA and ALA compete for the same enzymes. It is not known whether there is a difference between n-3 and n-6 FA of plant origin in the effects on serum lipid profile. AIM OF THE STUDY: To compare the effects of HO and FO on the profile of serum lipids and fasting concentrations of serum total and lipoprotein lipids, plasma glucose and insulin, and haemostatic factors in healthy humans. METHODS: Fourteen healthy volunteers participated in the study. A randomised, double-blind crossover design was used.

[1949] Whelan J J Nutr. 2009;139(1):5–10. Dietary stearidonic acid is a long chain (n-3) polyunsaturated fatty acid with potential health benefits. 2009.

A review of dietary stearidonic acid as a long-chain (n-3) polyunsaturated fatty acid with potential health benefits.

[1950] Da Porto C, et al. Eur J Lipid Sci Technol. 2014. Hempseed oil: chemical composition and functional properties. 2014.

An article on the chemical composition and functional properties of hempseed oil.

[1951] Leizer C, et al. J Nutraceuticals Funct Med Foods. 2000;2:35–53. The composition of hemp seed oil and its potential as an important source of nutrition. 2000.

An article on the composition of hemp seed oil and its potential as a source of nutrition.

[1952] Crescente G, et al. Phytochem Rev. 2018;17:733–749. Chemical composition and nutraceutical properties of hempseed. 2018.

A review of the chemical composition and nutraceutical properties of hempseed.

[1953] . Health Canada 1998. Industrial Hemp Regulations. 1998.

Health Canada's Industrial Hemp Regulations.

[1954] Du Toit G, et al. N Engl J Med. 2015;372(9):803–813. Randomized trial of peanut consumption in infants at risk for peanut allergy (LEAP study). 2015. Link

The LEAP randomized trial on peanut consumption in infants at risk for peanut allergy.

[1955] Jiang R, et al. JAMA. 2002;288(20):2554–2560. Nut and peanut butter consumption and risk of type 2 diabetes in women. 2002. Link

CONTEXT: Nuts are high in unsaturated (polyunsaturated and monounsaturated) fat and other nutrients that may improve glucose and insulin homeostasis. OBJECTIVE: To examine prospectively the relationship between nut consumption and risk of type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 83 818 women from 11 states in the Nurses' Health Study. The women were aged 34 to 59 years, had no history of diabetes, cardiovascular disease, or cancer, completed a validated dietary questionnaire at baseline in 1980, and were followed up for 16 years. MAIN OUTCOME MEASURE: Incident cases of type 2 diabetes. RESULTS: We documented 3206 new cases of type 2 diabetes.

[1956] Kris-Etherton PM, et al. Am J Clin Nutr. 1999;70(3 Suppl):504S–511S. Nuts and their bioactive constituents: effects on serum lipids. 1999.

A review of nuts and their bioactive constituents and their effects on serum lipids.

[1957] Tey SL, et al. Eur J Clin Nutr. 2015;69:117–123. A randomized intervention trial to determine the effect of hazelnut consumption on serum lipids and lipoproteins. 2015. Link

A randomized intervention trial on the effect of hazelnut consumption on serum lipids and lipoproteins.

[1958] Mateos R, et al. Nutrients. 2018;10(11):1631. Hazelnuts (Corylus avellana L.) bioactives and human health. 2018.

A review of hazelnuts (Corylus avellana L.) bioactives and human health.

[1959] Sicherer SH, et al. J Allergy Clin Immunol. 2010;125(6):1322–1326. US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up. 2010. Link

BACKGROUND: Allergy to peanuts and tree nuts (TNs) is the leading cause of fatal allergic reactions in the United States, and the prevalence appears to be increasing. OBJECTIVES: We sought to determine the US prevalence of self-reported peanut, TN, and sesame allergy in 2008 and compare results with comparable surveys conducted in 1997 and 2002. METHODS: A nationwide, cross-sectional, random telephone survey for peanut and TN allergy was conducted with a previously used questionnaire, with additional questions about sesame. RESULTS: A total of 5,300 households (13,534 subjects) were surveyed (participation rate, 42\% vs 52\% in 2002 and 67\% in 1997). Peanut allergy, TN allergy, or both was reported by 1.4\% of subjects (95\% CI, 1.2\% to 1.6\%) compared with 1.2\% in 2002 and 1.4\% in 1997. For adults, the prevalence was 1.3\% (95\% CI, 1.1\% to 1.6\%), which was not significantly different from prior surveys.

[1960] Davis L, et al. J Food Sci Technol. 2016;53(1):31–41. Peanuts as functional food: a review. 2016.

A review of peanuts as a functional food.

[1962] Mahmassani HA, Avendano EE, Raman G, Johnson EJ. Avocado consumption and risk factors for heart disease: a systematic review and meta-analysis2018;107(4):523–536. Am J Clin Nutr. Link

BACKGROUND: Nutrients in avocados are associated with cardiovascular benefits. OBJECTIVE: The aim of this study was to determine the effect of avocado intake on cardiovascular disease (CVD) risk with the use of a systematic review and meta-analysis. DESIGN: MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau abstracts were searched from 1946 through September 2017 for publications on avocado intake and CVD risk. All designs except for cross-sectional studies that evaluated avocado intake were included. Two investigators independently screened citations and extracted data. Random-effects models meta-analysis was used when ≥3 studies reported the same outcome.

[1963] Henning SM et al. Hass avocado inclusion in a weight-loss diet supported weight loss and altered gut microbiota2019;3(8):nzz068. Curr Dev Nutr. Link

BACKGROUND: Avocados contain fiber, lutein, and vitamin E, and they are a rich source of MUFAs. The effect of including an avocado daily as part of a hypocaloric weight-loss diet on weight loss is not known. OBJECTIVE: The aim of this study was to determine the effect of daily avocado consumption as part of a hypocaloric diet on weight loss, body composition, satiety, biomarkers of inflammation, and intestinal microbiota composition. METHODS: In this randomized, parallel-controlled, open-label, 2-arm intervention study, 51 healthy overweight/obese women and men were assigned to a hypocaloric diet with 1 Hass avocado daily (AVO; n = 24) or a hypocaloric diet (CTRL; n = 27) without daily avocado for 12 wk. Serum markers and intestinal microbiota were analyzed at baseline and week 12. RESULTS: Both groups experienced significant weight loss, decrease in BMI (in kg/m2), total body fat, and visceral adipose tissue, respectively (AVO: -2.3 ± 2 kg, -0.8 ± 0.8, -1.1\% ± 2\%, and -81.2 ± 118 g; CTRL: -2.6 ± 3.6 kg, -0.9 ± 1, -1.5\% ± 2\%, and -87.4 ± 216 g).

[1964] Berasategi I et al. Stability of avocado oil during heating: comparative study to olive oil 2012. Food Chem. 2012. Link

Experimental study of the thermal stability of avocado oil during heating at 180 °C, compared with olive oil at different heating times (0–9 h). Avocado oil showed higher PUFA/SFA and ω-6/ω-3 ratios throughout the experiment and was initially richer in total phytosterols than olive oil. The lipid-oxidation marker (TBARs) was higher in olive oil after 3 h, reaching its maximum in both oils at 6 h of heating.

[1965] Green HS et al. Authenticity of avocado oil — adulteration in the US commercial market 2020. Food Control. 2020.

A study on the authenticity of avocado oil and adulteration in the US commercial market.

[1966] Carvajal-Zarrabal O et al. Avocado oil supplementation modifies cardiovascular risk profile markers 2014. J Nutr Metab. 2014.

A study on avocado oil supplementation modifying cardiovascular risk profile markers.

[1967] Pieterse Z et al. Substitution of high monounsaturated fatty acid avocado for mixed dietary fats during an energy-restricted diet 2005. Nutrition. 2005. Link

Randomised, controlled, parallel study in 61 overweight/obese volunteers on substituting 200 g/day of high-monounsaturated-fat avocado for 30 g of mixed dietary fat within an energy-restricted diet. Including 200 g/day of avocado did not compromise weight loss relative to mixed fat. Serum lipids, fibrinogen, blood pressure, and arterial compliance did not change significantly within or between groups.

[1968] EFSA Panel on Dietetic Products. Scientific opinion on plant sterols and blood cholesterol2010;8(10):1813. EFSA Journal. Link

An EFSA scientific opinion on plant sterols and blood cholesterol.

[1969] Bang HO, Dyerberg J. Plasma lipid and lipoprotein pattern in Greenlandic West-Coast Eskimos1971;1(7710):1143–1145. Lancet. Link

An article on the plasma lipid and lipoprotein pattern in Greenlandic West-Coast Eskimos.

[1970] Bhatt DL et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia (REDUCE-IT)2019;380(1):11–22. NEJM. 2019. Link

A report from the REDUCE-IT trial on cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia.

[1971] Manson JE et al. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer (VITAL)2019;380(1):23–32. NEJM. 2019. Link

A report from the VITAL trial on marine n-3 fatty acids and the prevention of cardiovascular disease and cancer.

[1972] Nicholls SJ et al. Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events (STRENGTH)2020;324(22):2268–2280. JAMA. 2020. Link

IMPORTANCE: It remains uncertain whether the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular risk. OBJECTIVE: To determine the effects on cardiovascular outcomes of a carboxylic acid formulation of EPA and DHA (omega-3 CA) with documented favorable effects on lipid and inflammatory markers in patients with atherogenic dyslipidemia and high cardiovascular risk. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial (enrollment October 30, 2014, to June 14, 2017; study termination January 8, 2020; last patient visit May 14, 2020) comparing omega-3 CA with corn oil in statin-treated participants with high cardiovascular risk, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL-C). A total of 13 078 patients were randomized at 675 academic and community hospitals in 22 countries in North America, Europe, South America, Asia, Australia, New Zealand, and South Africa. INTERVENTIONS: Participants were randomized to receive 4 g/d of omega-3 CA (n = 6539) or corn oil, which was intended to serve as an inert comparator (n = 6539), in addition to usual background therapies, including statins. MAIN OUTCOMES AND MEASURES: The primary efficacy measure was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization.

[1973] EFSA NDA Panel. Scientific Opinion on Dietary Reference Values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol2010;8(3):1461. EFSA Journal. Link

An EFSA scientific opinion on dietary reference values for fats, including saturated, polyunsaturated, monounsaturated, trans fatty acids, and cholesterol.

[1974] Watson H et al. A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota2018;67(11):1974–1983. Gut. 1974. Link

OBJECTIVE: Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). DESIGN: A randomised, open-label, cross-over trial of 8 weeks' treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week 'washout' period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing.

[1975] Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology2014;19(1):21–36. Cell Metab. Link

A review of pro-resolving lipid mediators as leads for resolution physiology.

[1976] FDA. Advice About Eating Fish: Guidance on mercury content and safe consumption (updated 2021). . 2021.

FDA advice on eating fish, with guidance on mercury content and safe consumption.

[1977] MSC (Marine Stewardship Council). Certified sustainable seafood guidelines.

The Marine Stewardship Council (MSC) certified sustainable seafood guidelines.

[1978] USDA FoodData Central. Crassostrea gigas, Mytilus edulis tápértékadatai.

USDA FoodData Central nutritional data for Crassostrea gigas and Mytilus edulis.

[1979] EFSA Panel. Scientific Opinion on Vibrio in food (raw bivalves). EFSA Journal 2012. . 2012.

An EFSA scientific opinion on Vibrio in food (raw bivalves).

[1980] Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev 2013 (2017 update). . 2013. Link

A Cochrane systematic review on zinc for the common cold.

[1981] EFSA Panel. Tolerable Upper Intake Level for zinc (25 mg/day). EFSA Journal 2006. . 2006.

An EFSA opinion on the tolerable upper intake level for zinc (25 mg/day).

[1982] CDC. Vibrio infections after eating raw oysters. MMWR Reports.

CDC reports (MMWR) on Vibrio infections after eating raw oysters.

[1983] FAO. The State of World Fisheries and Aquaculture (SOFIA) 2020 — Bivalve aquaculture sustainability. . 2020.

The FAO State of World Fisheries and Aquaculture (SOFIA) 2020 report, on bivalve aquaculture sustainability.

[1984] Aquaculture Stewardship Council. ASC Bivalve Standard.

The Aquaculture Stewardship Council (ASC) Bivalve Standard.

[1985] Marine Stewardship Council (MSC). Bivalve fishery certification.

Marine Stewardship Council (MSC) document on the certification of bivalve fisheries.

[1986] EFSA Panel. Norovirus in oysters and bivalve molluscs. EFSA Journal 2019. . 2019.

2019 EFSA Panel scientific opinion on norovirus in oysters and other bivalve molluscs.

[1987] Asnicar F et al. Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals (ZOE PREDICT 1)2021;27(2):321–332. Nat Med. 2021. Link

Observational study by Asnicar et al (ZOE PREDICT 1) on microbiome connections with host metabolism and habitual diet in 1,098 deeply phenotyped individuals.

[1988] WHO. Sodium intake recommendation (< 2 g/day, 2012). . 2012.

WHO 2012 sodium intake recommendation (< 2 g/day).

[1989] USDA FoodData Central. Loligo, Octopus, Sepia tápértékadatai.

USDA FoodData Central nutrient data for Loligo (squid), Octopus, and Sepia.

[1990] Albertin CB et al. The octopus genome. Nature 2015;524:220–224. . 2015. Link

Nature paper by Albertin et al on the sequencing and characterization of the octopus genome.

[1991] Waldron M et al. The effects of taurine on cardiovascular function and exercise performance. Adv Exp Med Biol 2018. . 2018.

Review by Waldron et al on the effects of taurine on cardiovascular function and exercise performance.

[1992] EFSA Panel. Mercury in fishery products. EFSA Journal 2012. . 2012.

2012 EFSA Panel scientific opinion on mercury in fishery products.

[1993] USDA. 2015–2020 Dietary Guidelines, cholesterol revision. . 2015.

USDA 2015–2020 Dietary Guidelines, including the revision of the cholesterol recommendation.

[1994] Birch J et al. Review of the evidence of sentience in cephalopod molluscs. LSE Animal Sentience 2021. . 2021.

Review by Birch et al of the evidence for sentience in cephalopod molluscs.

[1995] Marine Stewardship Council (MSC). Cephalopod fishery assessment.

Marine Stewardship Council (MSC) document on cephalopod fishery assessment.

[1996] EFSA Panel. Anisakis and other fishborne parasites. EFSA Journal 2010. . 2010.

2010 EFSA Panel scientific opinion on Anisakis and other fishborne parasites.

[1997] FAO. SOFIA Report 2020 — Cephalopod fisheries. . 2020.

Section of the FAO 2020 SOFIA Report dealing with cephalopod fisheries.

[1999] USDA FoodData Central. Trout, rainbow, farmed, raw — Nutrient profile. 2024. . 2024.

USDA FoodData Central nutrient profile for farmed, raw rainbow trout (2024).

[2000] Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease. JACC 2011;58(20):2047–2067. . 2011. Link

Review by Mozaffarian and Wu on omega-3 fatty acids and cardiovascular disease (JACC).

[2001] FDA. Advice about eating fish — choices for women who are pregnant or breastfeeding. 2022 update. . 2022.

FDA 2022 updated advice about eating fish for women who are pregnant or breastfeeding.

[2002] Charoenngam N, Holick MF. Immunologic effects of vitamin D on human health and disease. Nutrients 2020;12(7):2097. . 2020. Link

Review by Charoenngam and Holick on the immunologic effects of vitamin D on human health and disease (Nutrients).

[2003] Bashir M et al. Effects of high doses of vitamin D3 on mucosa-associated gut microbiome. Eur J Nutr 2016;55:1479–1489. . 2016. Link

PURPOSE: Vitamin D is well known for its effects on bone mineralisation but has also been attributed immunomodulatory properties. It positively influences human health, but in vivo data describing vitamin D effects on the human gut microbiome are missing. We aimed to investigate the effects of oral vitamin D3 supplementation on the human mucosa-associated and stool microbiome as well as CD8(+) T cells in healthy volunteers. METHODS: This was an interventional, open-label, pilot study. Sixteen healthy volunteers (7 females, 9 males) were endoscopically examined to access a total of 7 sites. We sampled stomach, small bowel, colon, and stools before and after 8 weeks of vitamin D3 supplementation.

[2004] EFSA. Scientific opinion on dietary reference values for fats, EPA, DHA. EFSA Journal 2010;8(3):1461. . 2010. Link

EFSA scientific opinion on dietary reference values for fats, EPA, and DHA.

[2005] Devassy JG et al. Omega-3 polyunsaturated fatty acids and oxylipins in neuroinflammation and management of Alzheimer's disease. Adv Nutr 2016;7:905–916. . 2016. Link

Review of the role of omega-3 polyunsaturated fatty acids (EPA, DHA) and their derived oxylipins in neuroinflammation and the management of Alzheimer disease. The authors argue that neuroinflammation contributes to Alzheimer progression, while n-3 PUFAs are involved in reducing and resolving inflammation through bioactive lipid mediators. Both DHA and EPA may reduce neuroinflammation and cognitive decline.

[2006] Aquaculture Stewardship Council (ASC). Trout certification standards. 2023. . 2023.

Aquaculture Stewardship Council (ASC) trout certification standards (2023).

[2007] Magyar Tudományos Akadémia. Hazai pisztrángtenyésztés helyzete — Halászati közlemények 2018. . 2018.

Hungarian Academy of Sciences review on the state of domestic trout farming, in Halászati közlemények (2018).

[2008] USDA FoodData Central. Herring, Atlantic, cooked, dry heat — Nutrient profile. 2024. . 2024.

USDA FoodData Central nutrient profile for Atlantic herring cooked with dry heat (2024).

[2009] Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health. JAMA 2006;296(15):1885–1899. . 2006. Link

CONTEXT: Fish (finfish or shellfish) may have health benefits and also contain contaminants, resulting in confusion over the role of fish consumption in a healthy diet. EVIDENCE ACQUISITION: We searched MEDLINE, governmental reports, and meta-analyses, supplemented by hand reviews of references and direct investigator contacts, to identify reports published through April 2006 evaluating (1) intake of fish or fish oil and cardiovascular risk, (2) effects of methylmercury and fish oil on early neurodevelopment, (3) risks of methylmercury for cardiovascular and neurologic outcomes in adults, and (4) health risks of dioxins and polychlorinated biphenyls in fish. We concentrated on studies evaluating risk in humans, focusing on evidence, when available, from randomized trials and large prospective studies. When possible, meta-analyses were performed to characterize benefits and risks most precisely. EVIDENCE SYNTHESIS: Modest consumption of fish (eg, 1-2 servings/wk), especially species higher in the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduces risk of coronary death by 36\% (95\% confidence interval, 20\%-50\%; P<.001) and total mortality by 17\% (95\% confidence interval, 0\%-32\%; P = .046) and may favorably affect other clinical outcomes. Intake of 250 mg/d of EPA and DHA appears sufficient for primary prevention.

[2010] Rimm EB et al. Seafood Long-Chain n-3 Polyunsaturated Fatty Acids and Cardiovascular Disease. AHA Science Advisory. Circulation 2018;138:e35–e47. . 2018. Link

AHA Science Advisory by Rimm et al on seafood long-chain n-3 polyunsaturated fatty acids and cardiovascular disease (Circulation).

[2011] GISSI-Prevenzione Investigators. Dietary supplementation with n-3 PUFAs after myocardial infarction. Lancet 1999;354:447–455. . 1999. Link

BACKGROUND: There is conflicting evidence on the benefits of foods rich in vitamin E (alpha-tocopherol), n-3 polyunsaturated fatty acids (PUFA), and their pharmacological substitutes. We investigated the effects of these substances as supplements in patients who had myocardial infarction. METHODS: From October, 1993, to September, 1995, 11,324 patients surviving recent (< or = 3 months) myocardial infarction were randomly assigned supplements of n-3 PUFA (1 g daily, n=2836), vitamin E (300 mg daily, n=2830), both (n=2830), or none (control, n=2828) for 3.5 years. The primary combined efficacy endpoint was death, non-fatal myocardial infarction, and stroke. Intention-to-treat analyses were done according to a factorial design (two-way) and by treatment group (four-way). FINDINGS: Treatment with n-3 PUFA, but not vitamin E, significantly lowered the risk of the primary endpoint (relative-risk decrease 10\% [95\% CI 1-18] by two-way analysis, 15\% [2-26] by four-way analysis).

[2013] Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr 2007;85(5):1185–1196. . 2007. Link

Review by Maintz and Novak on histamine and histamine intolerance (Am J Clin Nutr).

[2014] FDA. Advice about eating fish — choices for women who are pregnant or breastfeeding. 2022. . 2022.

FDA 2022 advice about eating fish for women who are pregnant or breastfeeding.

[2015] Marine Stewardship Council (MSC). Atlantic herring fisheries — certified sustainable. 2024. . 2024.

Marine Stewardship Council (MSC) certification of Atlantic herring fisheries as sustainable (2024).

[2016] Charoenngam N, Holick MF. Immunologic effects of vitamin D. Nutrients 2020;12(7):2097. . 2020. Link

Review by Charoenngam and Holick on the immunologic effects of vitamin D (Nutrients).

[2017] USDA FoodData Central. Sardines, Atlantic, canned in oil, with bones — Nutrient profile. 2024. . 2024.

USDA FoodData Central nutrient profile for Atlantic sardines canned in oil with bones (2024).

[2019] Rimm EB et al. Seafood and CVD: AHA Science Advisory. Circulation 2018;138:e35–e47. . 2018. Link

AHA Science Advisory by Rimm et al on seafood and cardiovascular disease (Circulation).

[2020] Soares MJ et al. Sardine consumption and bone mineral density. Br J Nutr 2019;121:1242–1250. . 2019.

Study by Soares et al on sardine consumption and bone mineral density (Br J Nutr).

[2021] Mortensen SA et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure (Q-SYMBIO). JACC Heart Fail 2014;2:641–649. . 2014. Link

Q-SYMBIO clinical trial by Mortensen et al on the effect of coenzyme Q10 on morbidity and mortality in chronic heart failure (JACC Heart Fail).

[2022] Buettner D. The Blue Zones: 9 Lessons for Living Longer. National Geographic 2012. . 2012.

Popular-science book by Buettner (The Blue Zones, National Geographic) presenting 9 lessons for living longer.

[2025] Marine Stewardship Council (MSC). Sardine fisheries — certified sustainable. 2024. . 2024.

Marine Stewardship Council (MSC) certification of sardine fisheries as sustainable (2024).

[2026] USDA FoodData Central. Tuna, fresh, bluefin, raw / Tuna, light, canned in water — Nutrient profile. 2024. . 2024.

USDA FoodData Central nutrient profiles for fresh raw bluefin tuna and light tuna canned in water (2024).

[2027] FDA / EPA. Advice about eating fish — choices for women who are pregnant or breastfeeding. 2024 update. . 2024.

FDA / EPA 2024 updated advice about eating fish for women who are pregnant or breastfeeding.

[2028] Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health. JAMA 2006;296:1885–1899. . 2006. Link

[2029] Ralston NVC, Raymond LJ. The "SeHBV" concept: selenium health benefit value as a measure of mercury risk. Toxicol Appl Pharmacol 2018. . 2018.

Paper by Ralston and Raymond on the "SeHBV" (selenium health benefit value) concept as a measure of mercury risk (Toxicol Appl Pharmacol).

[2030] Karimi R et al. Mercury and selenium in commercial fish from the New York metropolitan area. Environ Res 2014;134:248–254. . 2014.

Study by Karimi et al on mercury and selenium in commercial fish from the New York metropolitan area (Environ Res).

[2031] WHO. Methylmercury — JECFA tolerable weekly intake. WHO Food Additives Series 2010. . 2010.

WHO/JECFA document on the tolerable weekly intake of methylmercury (WHO Food Additives Series).

[2032] IUCN Red List. Thunnus thynnus (Atlantic bluefin tuna) — Endangered. 2024. . 2024.

IUCN Red List assessment classifying Thunnus thynnus (Atlantic bluefin tuna) as Endangered (2024).

[2034] Marine Stewardship Council. Tuna fisheries — certified sustainable list. 2024. . 2024.

Marine Stewardship Council list of tuna fisheries certified as sustainable (2024).

[2035] USDA FoodData Central. Salmon, Atlantic, wild, cooked / Salmon, Atlantic, farmed, cooked / Salmon, sockeye, wild, cooked — Nutrient profiles. 2024. . 2024. Link

USDA FoodData Central nutrient database entries for cooked wild and farmed Atlantic salmon and cooked wild sockeye (red) salmon. The entries provide detailed macro- and micronutrient profiles (water, protein, fat, plus fatty acids including EPA and DHA), serving as reference data for nutritional comparison across salmon types. (Database record, not a standalone research study.)

[2038] Hites RA et al. Global assessment of organic contaminants in farmed salmon. Science 2004;303:226–229. . 2004. Link

The annual global production of farmed salmon has increased by a factor of 40 during the past two decades. Salmon from farms in northern Europe, North America, and Chile are now available widely year-round at relatively low prices. Salmon farms have been criticized for their ecological effects, but the potential human health risks of farmed salmon consumption have not been examined rigorously. Having analyzed over 2 metric tons of farmed and wild salmon from around the world for organochlorine contaminants, we show that concentrations of these contaminants are significantly higher in farmed salmon than in wild. European-raised salmon have significantly greater contaminant loads than those raised in North and South America, indicating the need for further investigation into the sources of contamination. Risk analysis indicates that consumption of farmed Atlantic salmon may pose health risks that detract from the beneficial effects of fish consumption.

[2039] Sprague M et al. Impact of sustainable feeds on omega-3 long-chain fatty acid levels in farmed Atlantic salmon. Sci Rep 2016;6:21892. . 2016. Link

Study by Sprague et al on the impact of sustainable feeds on omega-3 long-chain fatty acid levels in farmed Atlantic salmon (Sci Rep).

[2040] Costantini L et al. Impact of omega-3 fatty acids on the gut microbiota. Int J Mol Sci 2017;18(12):2645. . 2017. Link

Review by Costantini et al on the impact of omega-3 fatty acids on the gut microbiota (Int J Mol Sci).

[2041] Goto S et al. Efficient radical trapping at the surface and inside of the phospholipid membrane by astaxanthin. Biochim Biophys Acta 2001;1512:251–258. . 2001. Link

Paper by Goto et al on efficient radical trapping at the surface and inside of the phospholipid membrane by astaxanthin (Biochim Biophys Acta).

[2042] EFSA. Scientific opinion on the safety of farmed salmon. EFSA Journal 2014. . 2014.

2014 EFSA scientific opinion on the safety of farmed salmon.

[2043] ASC (Aquaculture Stewardship Council). Salmon Standard. 2024. . 2024.

Aquaculture Stewardship Council (ASC) Salmon Standard certification document (2024).

[2044] FDA. Advice about eating fish — choices for women who are pregnant or breastfeeding. 2024. . 2024.

FDA 2024 advice about eating fish for women who are pregnant or breastfeeding.

[2045] USDA FoodData Central. Caviar, Salmon roe, Trout roe tápértékadatai.

USDA FoodData Central nutrient data for caviar, salmon roe, and trout roe.

[2046] EFSA Panel. DHA reference value in pregnancy (200 mg/day). EFSA Journal 2014. . 2014.

2014 EFSA Panel scientific opinion on the DHA reference value in pregnancy (200 mg/day).

[2047] CITES. Sturgeon trade ban — Appendix II. 2006. . 2006.

2006 CITES measure restricting sturgeon trade through Appendix II listing.

[2048] Schuchardt JP et al. Bioavailability of marine n-3 fatty acid formulations. Prostaglandins Leukot Essent Fatty Acids 2011;85(3-4):109–114. . 2011.

Study by Schuchardt et al on the bioavailability of marine n-3 fatty acid formulations (Prostaglandins Leukot Essent Fatty Acids).

[2049] MSC. Alaskan salmon roe (ikura) certification.

MSC certification relating to Alaskan salmon roe (ikura).

[2050] EFSA Panel. Listeria monocytogenes in fishery products. EFSA Journal 2018. . 2018.

A 2018 EFSA Panel scientific opinion on the risk of Listeria monocytogenes in fishery products.

[2054] . Calvisius / Petrossian sustainability reports.

Sustainability reports of the Calvisius and Petrossian caviar companies as corporate sources.

[2055] USDA FoodData Central. Scomber scombrus, Scomber japonicus, Scomberomorus cavalla tápértékadatai.

USDA FoodData Central nutrient composition data for the mackerel species Scomber scombrus, Scomber japonicus and Scomberomorus cavalla.

[2056] Rimm EB et al. Seafood long-chain n-3 polyunsaturated fatty acids and cardiovascular disease — AHA Scientific Statement. Circulation 2018;138(1):e35–e47. . 2018. Link

An American Heart Association Scientific Statement (Circulation, 2018) on seafood long-chain n-3 polyunsaturated fatty acids and cardiovascular disease.

[2057] FDA. Advice About Eating Fish, fajspecifikus táblázat (king mackerel = Choices to Avoid).

The FDA "Advice About Eating Fish" species-specific table, in which king mackerel is listed under "Choices to Avoid".

[2058] EFSA Panel. EPA + DHA dietary reference value; Vitamin D reference value.

EFSA Panel dietary reference values for EPA + DHA intake and for vitamin D.

[2059] Bang HO, Dyerberg J. Plasma lipids and lipoproteins in Greenlandic west coast Eskimos. Acta Med Scand 1971;192:85–94. . 1971. Link

A 1971 study by Bang and Dyerberg (Acta Med Scand) on plasma lipids and lipoproteins in Greenlandic west coast Eskimos.

[2060] MSC. North-East Atlantic mackerel fishery certification.

An MSC (Marine Stewardship Council) certification of the North-East Atlantic mackerel fishery.

[2061] EMA. Tyramine-MAOI interaction guidance.

EMA (European Medicines Agency) guidance on the tyramine-MAOI interaction.

[2062] EFSA Panel. Histamine and other biogenic amines in fishery products. EFSA Journal 2011. . 2011.

A 2011 EFSA Panel scientific opinion on histamine and other biogenic amines in fishery products.

[2064] EFSA Panel. Listeria monocytogenes in smoked fish. EFSA Journal 2018. . 2018.

A 2018 EFSA Panel scientific opinion on Listeria monocytogenes in smoked fish.

[2065] USDA FoodData Central. Gadus morhua, Gadus macrocephalus tápértékadatai.

USDA FoodData Central nutrient composition data for the cod species Gadus morhua and Gadus macrocephalus.

[2066] Rimm EB et al. Seafood and CVD — AHA Scientific Statement. Circulation 2018. . 2018. Link

An American Heart Association Scientific Statement (Circulation, 2018) on seafood and cardiovascular disease.

[2067] FDA. Advice About Eating Fish, „Best Choices" lista (cod = Best Choice).

The "Best Choices" list of the FDA "Advice About Eating Fish" advisory, in which cod is listed as a "Best Choice".

[2068] EFSA Panel. Iodine reference value; Vitamin A pregnancy upper limit.

EFSA Panel reference values for iodine intake and the vitamin A upper limit in pregnancy.

[2069] Greer FR. 25-hydroxyvitamin D: functional outcomes in infants and young children. Pediatrics 2008. . 2008.

A 2008 article by Greer (Pediatrics) on 25-hydroxyvitamin D and functional outcomes in infants and young children.

[2070] ICES, MSC. North-East Atlantic cod stock assessment.

An ICES and MSC assessment of the North-East Atlantic cod stock.

[2071] Holmlund CM, Hammer M. Ecosystem services generated by fish populations — Grand Banks cod collapse. Ecol Econ 1999;29:253–268. . 1999. Link

Review/analytical paper on the ecosystem services generated by fish populations, based on documented ecological functions and human demands. The authors argue that overexploitation of global fish stocks threatens not only populations important for consumption and recreation but also numerous ecosystem services, with consequences for biodiversity, ecosystem functioning, and human welfare. The work is often cited to frame the broader ecological consequences of events such as the Grand Banks cod collapse.

[2074] EFSA Panel. Tolerable Upper Intake Level for vitamin A (3000 µg/day for pregnant women).

An EFSA Panel determination of the Tolerable Upper Intake Level for vitamin A (3000 µg/day for pregnant women).

[2075] USDA FoodData Central. Pleuronectes platessa, Solea solea, Hippoglossus hippoglossus tápértékadatai.

USDA FoodData Central nutrient composition data for the flatfish species Pleuronectes platessa, Solea solea and Hippoglossus hippoglossus.

[2077] FDA. Advice About Eating Fish, fajspecifikus táblázat (flounder/sole = Best Choices, halibut = Good Choices).

The species-specific table of the FDA "Advice About Eating Fish" advisory, in which flounder/sole are listed as "Best Choices" and halibut as "Good Choices".

[2078] EFSA Panel. Methylmercury TWI; iodine reference value.

EFSA Panel determinations of the methylmercury Tolerable Weekly Intake (TWI) and the iodine reference value.

[2079] MSC. Alaskan Pacific halibut, Icelandic plaice fishery certification.

An MSC certification of the Alaskan Pacific halibut and Icelandic plaice fisheries.

[2080] ICES. North Sea plaice and sole stock assessment.

An ICES stock assessment of North Sea plaice and sole.

[2081] EFSA Panel. Listeria monocytogenes in cold-smoked fish. EFSA Journal 2018. . 2018.

A 2018 EFSA Panel scientific opinion on Listeria monocytogenes in cold-smoked fish.

[2083] Escoffier A. Le Guide Culinaire, 1903 (Dover sole történeti receptúrák). . 1903.

Escoffier's 1903 cookbook Le Guide Culinaire, with historical recipes (Dover sole).

[2084] FAO. SOFIA Report 2020 — Flatfish fisheries. . 2020.

The FAO 2020 SOFIA report, section on flatfish fisheries.

[2085] USDA FoodData Central. Anguilla anguilla, Anguilla japonica tápértékadatai.

USDA FoodData Central nutrient composition data for the eel species Anguilla anguilla and Anguilla japonica.

[2087] EFSA Panel. EPA + DHA dietary reference value; Vitamin D reference; Vitamin A pregnancy upper limit (3000 µg/day).

EFSA Panel dietary reference values for EPA + DHA and vitamin D intake, and the vitamin A upper limit in pregnancy (3000 µg/day).

[2088] IUCN Red List. Anguilla anguilla — Critically Endangered (2008–2023 update). . 2008.

The IUCN Red List assessment classifying Anguilla anguilla as Critically Endangered (2008 assessment, with 2023 update).

[2089] CITES. Anguilla anguilla — Appendix II (2009). . 2009.

The CITES listing placing Anguilla anguilla in Appendix II (2009).

[2090] ASC. Aquaculture Stewardship Council Eel Standard.

The Aquaculture Stewardship Council (ASC) Eel Standard.

[2091] Schmidt J. The breeding places of the eel. Philos Trans R Soc B 1922;211:179–208. . 1922.

A 1922 paper by Schmidt (Philos Trans R Soc B) on the breeding places of the eel.

[2094] ICES Working Group on Eels (WGEEL). European eel stock assessment.

A stock assessment of the European eel by the ICES Working Group on Eels (WGEEL).

[2095] Ford AC et al. American College of Gastroenterology Monograph on Management of Irritable Bowel Syndrome and Chronic Idiopathic Constipation2014;109(Suppl 1):S2–S26. Am J Gastroenterol. Link

A 2014 American College of Gastroenterology monograph (Am J Gastroenterol) on the management of irritable bowel syndrome and chronic idiopathic constipation.

[2096] Ford AC et al. Efficacy of soluble fibre, antispasmodic drugs, and gut-brain neuromodulators in irritable bowel syndrome: a systematic review and network meta-analysis2022;7(11):975–991. Lancet Gastroenterol Hepatol. Link

A systematic review and network meta-analysis by Ford et al. (Lancet Gastroenterol Hepatol, 2022) on the efficacy of soluble fibre, antispasmodic drugs and gut-brain neuromodulators in irritable bowel syndrome.

[2097] Jalanka J et al. The Effect of Psyllium Husk on Intestinal Microbiota in Constipated Patients and Healthy Controls2019;9:14817. Sci Rep. Link

Psyllium is a widely used treatment for constipation. It traps water in the intestine increasing stool water, easing defaecation and altering the colonic environment. We aimed to assess the impact of psyllium on faecal microbiota, whose key role in gut physiology is being increasingly recognised. We performed two randomised, placebo-controlled, double-blinded trials comparing 7 days of psyllium with a placebo (maltodextrin) in 8 healthy volunteers and 16 constipated patients respectively. We measured the patients' gastrointestnal (GI) transit, faecal water content, short-chain fatty acid (SCFA) and the stool microbiota composition. While psyllium supplement had a small but significant effect on the microbial composition of healthy adults (increasing Veillonella and decreasing Subdoligranulum), in constipated subjects there were greater effects on the microbial composition (increased Lachnospira, Faecalibacterium, Phascolarctobacterium, Veillonella and Sutterella and decreased uncultured Coriobacteria and Christensenella) and alterations in the levels of acetate and propionate.

[2098] Gibb RD et al. Psyllium fiber improves glycemic control proportional to loss of glycemic control: a meta-analysis2015;102(6):1604–1614. AJCN. Link

BACKGROUND: A number of health benefits are associated with intake of soluble, viscous, gel-forming fibers, including reduced serum cholesterol and the attenuation of postprandial glucose excursions. OBJECTIVE: We assess the effects of psyllium, which is a soluble, gel-forming, nonfermented fiber supplement, on glycemic control in patients who were being treated for type 2 diabetes mellitus (T2DM) and in patients who were at risk of developing T2DM. DESIGN: A comprehensive search was performed of available published literature (Scopus scientific database) and clinical records stored by Procter \& Gamble with the use of key search terms to identify clinical studies that assessed the glycemic effects of psyllium in nondiabetic, pre-T2DM, and T2DM patients. RESULTS: We identified 35 randomized, controlled, clinical studies that spanned 3 decades and 3 continents. These data were assessed in 8 meta-analyses. In patients with T2DM, multiweek studies (psyllium dosed before meals) showed significant improvement in both the fasting blood glucose (FBG) concentration (-37.0 mg/dL; P < 0.001) and glycated hemoglobin (HbA1c) [-0.97\% (-10.6 mmol/mol); P = 0.048].

[2099] FDA. Soluble fiber from certain foods (psyllium) and risk of coronary heart disease. 21 CFR 101.81 (Health Claim, 1998). . 1998.

An FDA health claim (21 CFR 101.81, 1998) on soluble fiber from certain foods (psyllium) and the risk of coronary heart disease.

[2100] EFSA NDA Panel. Scientific Opinion on the substantiation of health claims related to psyllium () and maintenance of normal bowel function. EFSA Journal 2010;8(10):1747. Plantago ovata. 2010. Link

An EFSA NDA Panel scientific opinion (EFSA Journal, 2010) on the substantiation of health claims relating psyllium (Plantago ovata) to the maintenance of normal bowel function.

[2101] Smith BM et al. Gluten-free baking with psyllium husk: structural and nutritional benefits 2017. LWT-Food Science. 2017.

A 2017 article by Smith et al. (LWT-Food Science) on gluten-free baking with psyllium husk and its structural and nutritional benefits.

[2102] . NICE Guideline CG61 (updated 2017). Irritable bowel syndrome in adults: diagnosis and management. 2017.

The NICE CG61 guideline (updated 2017) on the diagnosis and management of irritable bowel syndrome in adults.

[2103] . Cochrane Database: Soluble dietary fibre for chronic idiopathic constipation (review).

A Cochrane review on soluble dietary fibre for chronic idiopathic constipation.

[2104] Ibn Sina (Avicenna) (Canon of Medicine), c. Ibn Sina (Avicenna) (Canon of Medicine), c. 1025. Al-Kánun fi-l-tibb.

Ibn Sina's (Avicenna) Al-Qanun fi al-Tibb (Canon of Medicine), c. 1025, a historical medical source.

[2105] EFSA Panel. Glucomannan and reduction of body weight / maintenance of normal blood cholesterol 2009, 2010. EFSA Journal. 2009.

An EFSA Panel scientific opinion (EFSA Journal, 2009, 2010) on glucomannan and reduction of body weight and maintenance of normal blood cholesterol.

[2106] . Commission Regulation (EU) No 432/2012 — Annex. . 2012.

The Annex to Commission Regulation (EU) No 432/2012 (list of permitted health claims).

[2107] Ho HV et al. Effect of glucomannan supplementation on plasma LDL — meta-analysis2017;105(5):1239–1247. Am J Clin Nutr. Link

A meta-analysis by Ho et al. (Am J Clin Nutr, 2017) on the effect of glucomannan supplementation on plasma LDL.

[2108] Musazadeh V et al. Glucomannan supplementation and serum lipids: updated meta-analysis 2024. BMC Cardiovasc Disord. 2024.

An updated meta-analysis by Musazadeh et al. (BMC Cardiovasc Disord, 2024) on glucomannan supplementation and serum lipids.

[2109] Chen HL et al. Konjac-glucomannan and constipation 2008. Am J Gastroenterol. 2008.

A 2008 article by Chen et al. (Am J Gastroenterol) on konjac-glucomannan and constipation.

[2110] Mirzababaei A et al. Glucomannan and glycemic control — meta-analysis 2022. Front Nutr. 2022.

A meta-analysis by Mirzababaei et al. (Front Nutr, 2022) on glucomannan and glycemic control.

[2111] FDA Import Alert 33-15 — mini konjak gels choking hazard. 2017+. . 2017.

FDA Import Alert 33-15 (2017+) on the choking hazard of mini konjac gels.

[2112] FDA Recall Notice — konjac mini cups choking deaths. FDA Recall Notice — konjac mini cups choking deaths. 2023. . 2023.

A 2023 FDA recall notice on choking deaths caused by konjac mini cups.

[2113] Calame W et al. Gum arabic establishes prebiotic functionality in healthy human volunteers — RCT2008;100(6):1269–1275. Br J Nutr. Link

The present study was undertaken to determine the prebiotic efficacy of gum arabic upon consumption by man for up to 4 weeks and, if any, to establish the dose-effect relationship. Human healthy volunteers consumed various daily doses (5, 10, 20, 40 g) of gum arabic (EmulGold) in water for up to 4 weeks. Daily consumption of water was taken as the negative control and that of 10 g inulin as the positive control. At 0, 1, 2 and 4 weeks quantification of bacterial numbers in stool samples was performed via real time-PCR techniques and questionnaires were filled in to account for potential drawbacks. The genera of Bifidobacteria and Lactobacilli were taken as potentially beneficial bacteria and those of Bacteroides, Clostridium difficile and Enterococci as potentially non-beneficial, this distinction was dependent on the issue of these numbers being or becoming out of balance in the host. Compared with the negative control the numbers of Bifidobacteria and Lactobacilli 4 weeks after consumption were significantly higher for gum arabic: the optimal dose being around 10 g.

[2114] Cherbut C et al. Acacia gum is a bifidogenic dietary fibre with high digestive tolerance2003. Microb Ecol Health Dis. Link

A 2003 article by Cherbut et al. (Microb Ecol Health Dis) describing acacia gum as a bifidogenic dietary fibre with high digestive tolerance.

[2115] Babiker R et al. Effects of Gum Arabic on body mass index in healthy adult females — RCT2012. Nutr J. Link

BACKGROUND: Gum Arabic (acacia Senegal) is a complex polysaccharide indigestible to both humans and animals. It has been considered as a safe dietary fiber by the United States, Food and Drug Administration (FDA) since the 1970s. Although its effects were extensively studied in animals, there is paucity of data regarding its quantified use in humans. This study was conducted to determine effects of regular Gum Arabic (GA) ingestion on body mass index and body fat percentage among healthy adult females. METHODS: A two-arm randomized, placebo controlled, double-blind trial was conducted in the Department of Physiology at the Khartoum University. A total of 120 healthy females completed the study.

[2116] Larson R et al. Acacia gum and postprandial responses2021. Nutrients. Link

Research paper examining acacia gum intake and postprandial responses.

[2117] EFSA Panel. Re-evaluation of gum arabic (E414) as food additive2017;15(5):4814. EFSA Journal. Link

EFSA Panel scientific opinion on the re-evaluation of gum arabic (E414) as a food additive.

[2118] JECFA. Gum arabic safety assessment. WHO Food Additives. Link

JECFA safety assessment of gum arabic, in the WHO Food Additives series.

[2119] Rawi MH et al. Gum arabic and SCFA production —2021. ACS Omega. 2021. Link

Research article examining gum arabic and SCFA production.

[2120] Marzorati M et al. Gum arabic slows down fermentation of co-substrates2015. J Funct Foods. Link

Research paper on how gum arabic slows down the fermentation of co-substrates.

[2121] Ramnani P et al. Prebiotic effect of agave fructans in healthy adults — randomized crossover2015. J Nutr Sci. Link

This placebo-controlled, randomised, double-blind, cross-over human feeding study aimed to determine the prebiotic effect of agave fructans. A total of thirty-eight volunteers completed this trial. The treatment consisted of 3 weeks' supplementation with 5 g/d of prebiotic agave fructan (Predilife) or equivalent placebo (maltodextrin), followed by a 2-week washout period following which subjects were crossed over to alternate the treatment arm for 3 weeks followed by a 2-week washout. Faecal samples were collected at baseline, on the last day of treatment (days 22 and 58) and washout (days 36 and 72), respectively. Changes in faecal bacterial populations, SCFA and secretory IgA were assessed using fluorescent in situ hybridisation, GC and ELISA, respectively. Bowel movements, stool consistencies, abdominal comfort and mood changes were evaluated by a recorded daily questionnaire.

[2122] Camacho-Díaz BH et al. Agave fructans–enriched functional food in IBS-C patients — RCT2023. Nutrients. Link

Irritable bowel syndrome displays three different subtypes: constipation (IBS-C), diarrhea (IBS-D), and mixed (IBS-M). Treatment with dietary fiber is used, with consideration given both to the chemical composition of the fiber and to the different subtypes of IBS. The IBS-D subtype is usually treated with a low-FODMAPs diet, whereas the IBS-C subtype suggests prebiotics and probiotics to promote microbiota restoration. The aim of this study was to assess the effects of employing agave fructans as the soluble fiber of a jelly (Gelyfun®gastro) containing 8 g per serving in the IBS-C group (n = 50), using a randomized, double-blind, time-limited trial for four weeks. We evaluated changes in the frequency and types of bowel movements through the Bristol scale, and the improvement of the condition was evaluated using quality of life (IBS-QOL) and anxiety-depression (HADS) scales. The main results were that the number of bowel movements increased by more than 80\%, with at least one stool per day from fifteen days onwards, without a laxative effect for the group treated.

[2123] Silva-Adame ME et al. Dose-tolerance of agavins in healthy adults — pilot RCT2022. Foods. Link

Pilot randomized controlled trial (Foods) on the dose-tolerance of agavins in healthy adults.

[2124] Franco-Robles E, López MG. Implication of fructans in health: structure-activity relationships2015. Glycobiology. Link

Previous studies have shown that fructans, a soluble dietary fiber, are beneficial to human health and offer a promising approach for the treatment of some diseases. Fructans are nonreducing carbohydrates composed of fructosyl units and terminated by a single glucose molecule. These carbohydrates may be straight or branched with varying degrees of polymerization. Additionally, fructans are resistant to hydrolysis by human digestive enzymes but can be fermented by the colonic microbiota to produce short chain fatty acids (SCFAs), metabolic by-products that possess immunomodulatory activity. The indirect role of fructans in stimulating probiotic growth is one of the mechanisms through which fructans exert their prebiotic activity and improve health or ameliorate disease. However, a more direct mechanism for fructan activity has recently been suggested; fructans may interact with immune cells in the intestinal lumen to modulate immune responses in the body.

[2125] Hughes RL et al. Inulin-type fructans and human health2022. Adv Nutr. Link

Review article (Adv Nutr) on inulin-type fructans and human health.

[2126] Le Bourgot C et al. GI tolerance of inulin-type fructans2022. Nutrients. Link

Dietary fibres are important in the human diet with multiple health benefits. This study aimed to determine the gastrointestinal tolerance of short-chain fructo-oligosaccharides (scFOS), well-known prebiotic fibres, at doses up to 40 g/d. An observational, connected, dose-ranging trial was conducted in 116 healthy volunteers. During the first week, the participants were instructed to consume their usual diet. During the second week, half of the subjects consumed 15 g scFOS per day, and the other half consumed 20 g scFOS per day. For the third week, the scFOS dose was doubled for all subjects.

[2127] FDA. GRN 1019 — agave mixed fructans GRAS no-questions letter. 2023. . 2023. Link

FDA GRAS no-questions letter (GRN 1019) on agave mixed fructans.

[2128] EU Commission. Regulation 2015/2314 — chicory inulin claim (not extended to agave). . 2015. Link

EU Commission Regulation 2015/2314 on the chicory inulin claim (not extended to agave).

[2129] Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics1995;125(6):1401–1412. J Nutr. Link

Because the human gut microbiota can play a major role in host health, there is currently some interest in the manipulation of the composition of the gut flora towards a potentially more remedial community. Attempts have been made to increase bacterial groups such as Bifidobacterium and Lactobacillus that are perceived as exerting health-promoting properties. Probiotics, defined as microbial food supplements that beneficially affect the host by improving its intestinal microbial balance, have been used to change the composition of colonic microbiota. However, such changes may be transient, and the implantation of exogenous bacteria therefore becomes limited. In contrast, prebiotics are nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacterial species already resident in the colon, and thus attempt to improve host health. Intake of prebiotics can significantly modulate the colonic microbiota by increasing the number of specific bacteria and thus changing the composition of the microbiota.

[2130] Roberfroid M et al. Prebiotic effects: metabolic and health benefits2010;104(Suppl 2):S1–S63. Br J Nutr. Link

The different compartments of the gastrointestinal tract are inhabited by populations of micro-organisms. By far the most important predominant populations are in the colon where a true symbiosis with the host exists that is a key for well-being and health. For such a microbiota, 'normobiosis' characterises a composition of the gut 'ecosystem' in which micro-organisms with potential health benefits predominate in number over potentially harmful ones, in contrast to 'dysbiosis', in which one or a few potentially harmful micro-organisms are dominant, thus creating a disease-prone situation. The present document has been written by a group of both academic and industry experts (in the ILSI Europe Prebiotic Expert Group and Prebiotic Task Force, respectively). It does not aim to propose a new definition of a prebiotic nor to identify which food products are classified as prebiotic but rather to validate and expand the original idea of the prebiotic concept (that can be translated in 'prebiotic effects'), defined as: 'The selective stimulation of growth and/or activity(ies) of one or a limited number of microbial genus(era)/species in the gut microbiota that confer(s) health benefits to the host.' Thanks to the methodological and fundamental research of microbiologists, immense progress has very recently been made in our understanding of the gut microbiota. A large number of human intervention studies have been performed that have demonstrated that dietary consumption of certain food products can result in statistically significant changes in the composition of the gut microbiota in line with the prebiotic concept.

[2131] Costabile A et al. A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke () in healthy human subjects. Br J Nutr 2010;104(7):1007–1017. Cynara scolymus. 2010. Link

[2133] Coudray C et al. Effect of soluble or partly soluble dietary fibres supplementation on absorption and balance of calcium, magnesium, iron and zinc in healthy young men1997. Eur J Clin Nutr. Link

OBJECTIVES: This study is aimed at investigating the effect of feeding a soluble or partly soluble fibre rich-diet on the apparent absorption and balance of calcium, magnesium, iron and zinc in healthy young men, by using a chemical balance technique. STUDY DESIGN: Nine healthy young men were given a control diet or the same diet complemented with either inulin (soluble) or sugar beet fibre (partly soluble) during 28 d periods according to a 3 x 3 latin square design with three repetitions. During the 20 d adaptation period to fibre ingestion, experimental fibres were incorporated into bread (60\%) and liquid foods (40\%) up to a maximum of 40 g/d. Ca, Mg, Fe and Zn were measured in diets and in a 8 d urine and faecal composites to assess mineral absorption and balance. RESULTS: The dietary mineral intake provided (mg/d) 859 +/- 196 of Ca; 311 +/- 43 of Mg; 11.6 +/- 1.7 of Fe; and 11.1 +/- 1.6 of Zn from the control diet. The apparent absorption of minerals from the control diet was (\%) Ca: 21.3 +/- 12.5; Mg: 46.3 +/- 10.9; Fe: 21.8 +/- 12.3 and Zn: 14.0 +/- 14.5 (mean +/- s.d.).

[2134] van den Heuvel EG et al. Oligofructose stimulates calcium absorption in adolescents1999;69(3):544–548. Am J Clin Nutr. Link

BACKGROUND: In rats, nondigestible oligosaccharides stimulate calcium absorption. Recently, this effect was also found in human subjects. OBJECTIVE: The objective of the study was to investigate whether consumption of 15 g oligofructose/d stimulates calcium absorption in male adolescents. DESIGN: Twelve healthy, male adolescents aged 14-16 y received, for 9 d, 15 g oligofructose or sucrose (control treatment) daily over 3 main meals. The treatments were given according to a randomized, double-blind, crossover design, separated by a 19-d washout period. On the 8th day of each treatment period, 44Ca was given orally with a standard breakfast containing approximately 200 mg Ca.

[2136] EFSA NDA Panel. Scientific opinion on fructooligosaccharides — health claims (rejected)2011. EFSA Journal. 2011. Link

EFSA NDA Panel scientific opinion on fructooligosaccharide health claims (rejected).

[2137] Davis LM, Martínez I, Walter J, Hutkins R. A dose dependent impact of prebiotic galactooligosaccharides on the intestinal microbiota of healthy adults2010;144(2):285–292. Int J Food Microbiol. Link

The goal of this research was to determine the effect of different doses of galactooligosaccharide (GOS) on the fecal microbiota of healthy adults, with a focus on bifidobacteria. The study was designed as a single-blinded study, with eighteen subjects consuming GOS-containing chocolate chews at four increasing dosage levels; 0, 2.5, 5.0, and 10.0g. Subjects consumed each dose for 3 weeks, with a two-week baseline period preceding the study and a two-week washout period at the end. Fecal samples were collected weekly and analyzed by cultural and molecular methods. Cultural methods were used for bifidobacteria, Bacteroides, enterobacteria, enterococci, lactobacilli, and total anaerobes; culture-independent methods included denaturing gradient gel electrophoresis (DGGE) and quantitative real-time PCR (qRT-PCR) using Bifidobacterium-specific primers. All three methods revealed an increase in bifidobacteria populations, as the GOS dosage increased to 5 or 10g.

[2138] Silk DB et al. Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome2009;29(5):508–518. Aliment Pharmacol Ther. Link

BACKGROUND: Gut microflora-mucosal interactions may be involved in the pathogenesis of irritable bowel syndrome (IBS). AIM: To investigate the efficacy of a novel prebiotic trans-galactooligosaccharide in changing the colonic microflora and improve the symptoms in IBS sufferers. METHODS: In all, 44 patients with Rome II positive IBS completed a 12-week single centre parallel crossover controlled clinical trial. Patients were randomized to receive either 3.5 g/d prebiotic, 7 g/d prebiotic or 7 g/d placebo. IBS symptoms were monitored weekly and scored according to a 7-point Likert scale. Changes in faecal microflora, stool frequency and form (Bristol stool scale) subjective global assessment (SGA), anxiety and depression and QOL scores were also monitored.

[2139] Schmidt K et al. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers2015;232(10):1793–1801. Psychopharmacology. Link

Study in healthy volunteers examining the effect of prebiotic intake on the waking cortisol response and emotional bias.

[2140] Boehm G et al. Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants2002;86(3):F178–F181. Arch Dis Child Fetal Neonatal Ed. Link

BACKGROUND: The establishment of a balanced intestinal microflora which may protect against infection is desirable for the preterm infant. OBJECTIVE: To investigate the effect of a preterm formula milk supplement consisting of oligosaccharides in similar proportions to human milk on the faecal flora and stool characteristics of preterm infants. STUDY DESIGN: To resemble the effect of human milk, an oligosaccharide mixture consisting of 90\% galacto-oligosaccharides and 10\% fructo-oligosaccharides was used to supplement a standard preterm formula at a concentration of 10 g/l. This supplemented formula was studied in 15 preterm infants, and the results were compared with those found in 15 infants fed a formula supplemented with maltodextrin as placebo. A group fed fortified mother's milk was investigated as a reference group (n = 12). On four days during a 28 day feeding period (1, 7, 14, and 28), the faecal flora was investigated, and stool characteristics, growth, and possible side effects were recorded.

[2141] Arslanoglu S et al. Early dietary intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and infections during the first two years of life2008;138(6):1091–1095. J Nutr. Link

A mixture of neutral short-chain galactooligosaccharides (scGOS) and long-chain fructooligosaccharides (lcFOS) has been shown to reduce the incidence of atopic dermatitis (AD) and infectious episodes during the first 6 mo of life. This dual protection occurred through the intervention period. The present study evaluated if these protective effects were lasting beyond the intervention period. In a prospective, randomized, double-blind, placebo-controlled design, healthy term infants with a parental history of atopy were fed either a prebiotic-supplemented (8 g/L scGOS/lcFOS) or placebo-supplemented (8 g/L maltodextrin) hypoallergenic formula during the first 6 mo of life. Following this intervention period, blind follow-up continued until 2 y of life. Primary endpoints were cumulative incidence of allergic manifestations.

[2143] Vandenplas Y et al. Oligosaccharides in infant formula: more evidence to validate the role of prebiotics2020. Br J Nutr. Link

The gastrointestinal (GI) microbiota differs between breast-fed and classic infant formula-fed infants. Breast milk is rich in prebiotic oligosaccharides (OS) and may also contain some probiotics, but scientific societies do not recommend the addition of prebiotic OS or probiotics to standard infant formula. Nevertheless, many infant formula companies often add one or the other or both. Different types of prebiotic OS are used in infant formula, including galacto-oligosaccharide, fructo-oligosaccharide, polydextrose and mixtures of these OS, but none adds human milk OS. There is evidence that the addition of prebiotics to infant formula brings the GI microbiota of formula-fed infants closer to that of breast-fed infants. Prebiotics change gut metabolic activity (by decreasing stool pH and increasing SCFA), have a bifidogenic effect and bring stool consistency and defecation frequency closer to those of breast-fed infants.

[2144] . FDA GRN 285, 484 — Vivinal GOS GRAS no-questions letters. Link

FDA GRAS no-questions letters (GRN 285, 484) on Vivinal GOS.

[2145] EFSA NDA Panel. Scientific opinion on the substantiation of a health claim related to oat beta-glucan and lowering of blood cholesterol2010;8(12):1885. EFSA Journal. Link

EFSA NDA Panel scientific opinion on the substantiation of a health claim relating oat beta-glucan to lowering blood cholesterol.

[2146] FDA. Health claim — soluble fiber from oats (beta-glucan) and coronary heart disease. 21 CFR 101.81 (1997). . 1997. Link

FDA health claim (21 CFR 101.81) on soluble fiber from oats (beta-glucan) and coronary heart disease.

[2148] Anderson JW et al. Hypocholesterolemic effects of oat-bran or bean intake for hypercholesterolemic men1984;40(6):1146–1155. Am J Clin Nutr. Link

Oat or bean products, rich in water-soluble fiber, have distinct hypocholesterolemic effects in humans. After a control diet, 20 hypercholesterolemic men were randomly allocated to oat-bran or bean supplemented diets for 21 days on a metabolic ward. Control and test diets provided equivalent energy, fat, and cholesterol but test diets had twice more total and 3-fold more soluble fiber. Oat-bran diets decreased serum cholesterol concentrations by 19\% (p less than 0.0005) and calculated low-density lipoprotein cholesterol by 23\% (p less than 0.0025). Bean diets decreased serum cholesterol concentrations by 19\% (p less than 0.0005) and low-density lipoprotein cholesterol by 24\% (p less than 0.0005). Oat-bran increased fecal weight by 43\% but beans did not.

[2149] Tiwari U, Cummins E. Meta-analysis of the effect of β-glucan intake on blood cholesterol and glucose levels2011;27(10):1008–1016. Nutrition. Link

Meta-analysis examining the effect of β-glucan intake on blood cholesterol and glucose levels.

[2150] Talbott S, Talbott J. Effect of BETA 1,3/1,6 GLUCAN on upper respiratory tract infection symptoms and mood state in marathon athletes2009;8(4):509–515. J Sports Sci Med. Link

Study (J Sports Sci Med) on the effect of beta-1,3/1,6-glucan on upper respiratory tract infection symptoms and mood state in marathon athletes.

[2152] Velikonja A et al. Effects of a beta-glucan-enriched diet on the gut microbiota in adults with metabolic syndrome2019. J Funct Foods. Link

Study analyzing the effects of a beta-glucan-enriched diet on the gut microbiota in adults with metabolic syndrome.

[2153] Costabile A et al. Impact of polydextrose on the faecal microbiota: a double-blind, crossover, placebo-controlled feeding study in healthy human subjects2012;108(3):471–481. Br J Nutr. Link

In this placebo-controlled, double-blind, crossover human feeding study, the effects of polydextrose (PDX; 8 g/d) on the colonic microbial composition, immune parameters, bowel habits and quality of life were investigated. PDX is a complex glucose oligomer used as a sugar replacer. The main goal of the present study was to identify the microbial groups affected by PDX fermentation in the colon. PDX was shown to significantly increase the known butyrate producer Ruminococcus intestinalis and bacteria of the Clostridium clusters I, II and IV. Of the other microbial groups investigated, decreases in the faecal Lactobacillus-Enterococcus group were demonstrated. Denaturing gel gradient electrophoresis analysis showed that bacterial profiles between PDX and placebo treatments were significantly different.

[2154] Hengst C et al. Effects of polydextrose supplementation on intestinal microbiota and short-chain fatty acid production in healthy adults2009;60(Suppl 5):96–105. Int J Food Sci Nutr. Link

Study in healthy adults on the effects of polydextrose supplementation on the intestinal microbiota and short-chain fatty acid production.

[2155] Forssten SD et al. Influence of a probiotic combination on faecal bifidobacteria — polydextrose effect2014. Int J Food Sci Nutr. Link

Research article examining the influence of a probiotic combination on faecal bifidobacteria, including the polydextrose effect.

[2156] Flood MT, Auerbach MH, Craig SAS. A review of the clinical toleration studies of polydextrose in food2004;42(9):1531–1542. Food Chem Toxicol. Link

Polydextrose is a non-digestible 1 kcal/g polysaccharide used primarily as a sugar replacer and dietary fiber in foods. At typical use levels, polydextrose provides physiological effects similar to those of other dietary fibers. However, excessive consumption of non-digestible carbohydrates can lead to gastrointestinal distress. Nine clinical studies were conducted with polydextrose to evaluate the extent of such symptoms. These studies determined laxation endpoints in adults and children, and showed that polydextrose was better tolerated than most other low digestible carbohydrates (e.g. polyols). This is because of a higher molecular weight and partial colonic fermentation, leading to a lower risk of osmotic diarrhea.

[2157] Jie Z et al. Studies on the effects of polydextrose intake on physiologic functions in Chinese people2000;72(6):1503–1509. Am J Clin Nutr. Link

BACKGROUND: Previous studies showed that polydextrose has physiologic effects similar to those of dietary fiber. OBJECTIVE: Ingestion of 4, 8, and 12 g polydextrose/d was studied to determine the physiologic effects in Chinese subjects. DESIGN: In a placebo-controlled, randomized, double-blind study, we evaluated the effects of polydextrose ingestion on clinical biochemistry indexes, glycated hemoglobin, glucose tolerance, the glycemic index, bowel function, stool weight and pH, short-chain fatty acid production, fecal microflora, and cecal mucosa cell proliferation. RESULTS: Polydextrose had no significant effect on blood biochemistry indexes. Ingestion of 12 g polydextrose plus 50 g glucose resulted in a glycemic index of 89\% (compared with a glycemic index of 100\% after ingestion of 50 g glucose). Bowel function (frequency and ease of defecation) improved significantly and there were no reports of abdominal distention, abdominal cramps, diarrhea, or hypoglycemia.

[2158] Konig D et al. Polydextrose and reduction in postprandial glycaemic response 2012. Nutr J. 2012.

Research paper on polydextrose and the reduction in postprandial glycaemic response.

[2159] Astbury NM et al. Polydextrose results in a dose-dependent reduction in ad libitum energy intake at a subsequent test meal2014;111(8):1499–1505. Br J Nutr. Link

Previous studies have reported that polydextrose can reduce food intake; however, the optimal dose required to achieve this effect is currently unknown. The present study investigated the effects of consuming a range of doses of polydextrose on appetite and energy intake (EI) using a randomised within-subject, cross-over design. For this purpose, twenty-one participants (n 12 men, n 9 women) consumed an 837 kJ liquid preload containing 0 g (control), 6.3, 12.5 or 25 g polydextrose. Subjective appetite ratings were collected using visual analogue scales and an ad libitum test meal was served 90 min later. Participants recorded EI for the remainder of the day in a food diary. Test meal EI following the control preload (5756 (sem 423) kJ) was significantly higher than following the 6.3 g (5048 (sem 384) kJ), 12.5 g (4722 (sem 384) kJ) and 25 g (4362 (sem 316) kJ) preloads (P< 0.05), and EI following the 6.3 g preload was significantly higher than following the 25 g preload (P< 0.01).

[2160] EFSA ANS Panel. Re-evaluation of polydextrose (E 1200) as a food additive2017;15(1):4544. EFSA Journal. Link

EFSA ANS Panel scientific opinion on the re-evaluation of polydextrose (E 1200) as a food additive.

[2161] FDA. 21 CFR 172.841 (food additive) + 21 CFR 101.9 (dietary fiber recognition, 2016). . 2016. Link

FDA regulation: 21 CFR 172.841 (food additive) plus 21 CFR 101.9 (dietary fiber recognition, 2016).

[2162] Genta S, Cabrera W, Habib N et al. Yacon syrup: beneficial effects on obesity and insulin resistance in humans2009;28(2):182–187. Clin Nutr. Link

BACKGROUND \& AIMS: Syrup obtained from yacon roots could be well positioned as a nutraceutical product due to its high fructooligosaccharides content. We examined the beneficial effects and tolerance of yacon syrup on human health. METHODS: Obese and slightly dyslipidemic pre-menopausal women were studied over a 120-day period in a double-blind placebo-controlled experiment. We used two doses of yacon syrup, 0.29 g and 0.14 g fructooligosaccharides/kg/day. At the start and end of the study, anthropometric measurements, blood glucose, calcium, lipid and insulin concentrations and Homeostasis Model Assessment index were determined. RESULTS: The recommended daily consumption of yacon syrup with no undesirable gastrointestinal effects is 0.14 g fructooligosaccharides/kg.

[2163] Ojansivu I, Ferreira CL, Salminen S. Yacon, a new source of prebiotic oligosaccharides with a history of safe use2011;22(1):40–46. Trends Food Sci Technol. Link

Research article on yacon as a new source of prebiotic oligosaccharides with a history of safe use.

[2164] Habib NC et al. Yacon syrup and its effects on intestinal glucose absorption and postprandial glycemia2011. Clin Nutr. Link

Yacon is a root rich in fructooligosaccharides (FOS), which act as prebiotics. Numerous studies have shown promising results in the technological aspects of producing yacon syrup. However, uncertainties exist concerning whether yacon syrup can modulate postprandial glucose and lipid profiles. In order to assess the effect of yacon syrup on postprandial glucose, insulin and triglyceride (TG) responses, a randomized, crossover, double-blind clinical intervention with 40 women (20 normal weight and 20 grade I obese) was performed. Participants underwent two-arms of intervention with at least a one-week wash-out period between visits. On each intervention day, after 12 h of fasting, an aliquot of blood was collected.

[2166] . Monash University FODMAP database — yacon syrup high-FODMAP listing. Link

Monash University FODMAP database entry listing yacon syrup as high-FODMAP.

[2167] EFSA Panel on Dietetic Products. Scientific Opinion on Dietary Reference Values for iodine2014;12(5):3660. EFSA Journal. Link

EFSA Panel on Dietetic Products scientific opinion on dietary reference values for iodine.

[2168] Yeh TS et al. Iodine content of dried edible seaweeds2014. J Food Compost Anal. Link

Research paper examining the iodine content of dried edible seaweeds.

[2169] Barandiaran LN et al. Iodine reduction in kombu by soaking and boiling2024. Nature Sci Rep. Link

Research article on iodine reduction in kombu by soaking and boiling.

[2170] Izaola O et al. Wakame intervention in cardiometabolic outcomes 2020. Endocrinol Diabetes Nutr. 2020.

Intervention study analyzing the effect of wakame on cardiometabolic outcomes.

[2171] Rønne ME et al. Alginate utilization by human gut Bacteroides — PUL system2023. Nat Commun. Link

Humans consume alginate in the form of seaweed, food hydrocolloids, and encapsulations, making the digestion of this mannuronic acid (M) and guluronic acid (G) polymer of key interest for human health. To increase knowledge on alginate degradation in the gut, a gene catalog from human feces was mined for potential alginate lyases (ALs). The predicted ALs were present in nine species of the Bacteroidetes phylum, of which two required supplementation of an endo-acting AL, expected to mimic cross-feeding in the gut. However, only a new isolate grew on alginate. Whole-genome sequencing of this alginate-utilizing isolate suggested that it is a new Bacteroides ovatus strain harboring a polysaccharide utilization locus (PUL) containing three ALs of families: PL6, PL17, and PL38. The BoPL6 degraded polyG to oligosaccharides of DP 1-3, and BoPL17 released 4,5-unsaturated monouronate from polyM.

[2172] Paxman JR et al. Alginate-enriched bread reduces energy intake2008. Appetite. Link

Sodium alginate is a seaweed-derived fibre that has previously been shown to moderate appetite in models of acute feeding. The mechanisms underlying this effect may include slowed gastric clearance and attenuated uptake from the small intestine. In order to assess whether alginate could be effective as a means of appetite control in free-living adults, 68 males and females (BMI range: 18.50-32.81 kg/m(2)) completed this randomised, controlled two-way crossover intervention to compare the effects of 7 day daily ingestion of a strong-gelling sodium alginate formulation against a control. A sodium alginate with a high-guluronate content was chosen because, upon ingestion, it forms a strong gel in the presence of calcium ions. Daily preprandial ingestion of the sodium alginate formulation produced a significant 134.8 kcal (7\%) reduction in mean daily energy intake. This reduced energy intake was underwritten by significant reductions in mean daily carbohydrate, sugar, fat, saturated fat and protein intakes.

[2173] UK FSA. Hijiki and inorganic arsenic — consumer advice. 2010. . 2010. Link

UK FSA consumer advice on hijiki and inorganic arsenic.

[2174] Ikeda K. New seasonings — discovery of umami(English translation 2002, original 1909). Chem Senses. 2002. Link

Ikeda K's classic paper on new seasonings, the discovery of umami (1909 original, English translation 2002).

[2175] Watanabe F. Vitamin B12 sources and bioavailability. Exp Biol Med 2007;232(10):1266–1274. . 2007. Link

[2176] Watanabe F et al. Pseudovitamin B(12) is the predominant cobamide of an algal health food, spirulina tablets. J Agric Food Chem 1999;47(11):4736–4741. . 1999. Link

The vitamin B(12) concentration of an algal health food, spirulina (Spirulina sp.) tablets, was determined by both Lactobacillus leichmannii ATCC 7830 microbiological and intrinsic factor chemiluminescence methods. The values determined with the microbiological method were approximately 6-9-fold greater in the spirulina tablets than the values determined with the chemiluminescence method. Although most of the vitamin B(12) determined with the microbiological method was derived from various vitamin B(12) substitutive compounds and/or inactive vitamin B(12) analogues, the spirulina contained a small amount of vitamin B(12) active in the binding of the intrinsic factor. Two intrinsic factor active vitamin B(12) analogues (major and minor) were purified from the spirulina tablets and partially characterized. The major (83\%) and minor (17\%) analogues were identified as pseudovitamin B(12) and vitamin B(12), respectively, as judged from data of TLC, reversed-phase HPLC, (1)H NMR spectroscopy, ultraviolet-visible spectroscopy, and biological activity using L. leichmannii as a test organism and the binding of vitamin B(12) to the intrinsic factor.

[2177] Serban MC et al. A systematic review and meta-analysis of the impact of Spirulina supplementation on plasma lipid concentrations. Clin Nutr 2016;35(4):842–851. . 2016. Link

BACKGROUND \& AIMS: The impact of Spirulina supplementation on plasma lipid concentrations has not been conclusively studied. Therefore the aim of the meta-analysis was to assess the effect of Spirulina supplementation on plasma lipid concentrations. METHODS: We searched PubMed and Scopus (up to July 03, 2015) to identify randomized controlled trials (RCTs) that investigate the effect Spirulina supplementation on plasma lipid concentrations. Meta-analysis and meta-regression were performed using random-effects models. RESULTS: Random-effect meta-analysis of data from 7 RCTs showed a significant effect of supplementation with spirulina in reducing plasma concentrations of total cholesterol (WMD: -46.76 mg/dL, 95\% CI: -67.31 to -26.22, p < 0.001), LDL-C (WMD: -41.32 mg/dL, 95\% CI: -60.62 to -22.03, p < 0.001) and triglycerides (WMD: -44.23 mg/dL, 95\% CI: -50.22 to -38.24, p < 0.001), and elevating those of HDL-C (WMD: 6.06 mg/dL, 95\% CI: 2.37-9.76, p = 0.001). The impact of spirulina on plasma concentrations of total cholesterol (slope: -1.32; 95\% CI: -8.58 to 5.93; p = 0.720), LDL-C (slope: -1.01; 95\% CI: -8.03 to 6.02; p = 0.778), triglycerides (slope: -1.39; 95\% CI: -4.26 to 1.48; p = 0.342) and HDL-C (slope: 1.79, 95\% CI: -0.48 to 4.05; p = 0.122) was independent of administered dose.

[2178] Hamedifard Z et al. The effects of spirulina on glycemic control and serum lipoproteins in patients with metabolic syndrome and related disorders: a systematic review and meta-analysis. Phytother Res 2019;33(10):2609–2621. . 2019. Link

The aim of this systematic review and meta-analysis was to evaluate the effects of spirulina on glycemic control and serum lipoproteins in patients with metabolic syndrome (MetS) and related disorders. Two independent authors systematically searched online database including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until April 30, 2019. The Cochrane Collaboration's risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane's Q test and I-square (I2 ) statistic. Pooling effect sizes from studies showed a significant reduction in fasting plasma glucose (FPG; weighted mean difference [WMD]: -10.31; 95\% confidence interval, CI [-16.21, -4.42]) and insulin concentrations (WMD: -0.53; 95\% CI [-0.62, -0.44]) following the administration of spirulina. Pooled analysis showed also a significant reduction in total cholesterol (WMD: -20.50; 95\% CI [-38.25, -2.74]), low-density lipoprotein cholesterol (LDL-C; WMD: -19.02; 95\% CI [-36.27, -1.78]), and very low-density lipoprotein cholesterol (VLDL-C) concentrations (WMD: -6.72; 95\% CI [-9.19, -4.26]) and a significant increase in high-density lipoprotein cholesterol (HDL-C) levels (WMD: 1.42; 95\% CI [0.16, 2.68]) following spirulina therapy.

[2179] Karkos PD et al. Spirulina in clinical practice: evidence-based human applications. Evid Based Complement Alternat Med 2011:531053. . 2011. Link

Review on spirulina in clinical practice and its evidence-based human applications.

[2180] WHO/IIMSAM. Sustainable nutrition: spirulina algae as a tool against malnutrition. Position paper 2008. . 2008. Link

WHO/IIMSAM position paper on sustainable nutrition and spirulina algae as a tool against malnutrition.

[2181] EFSA. Scientific opinion on microalgae and cyanobacteria as food. EFSA Journal 2020. . 2020.

EFSA scientific opinion on microalgae and cyanobacteria as food.

[2182] Finamore A et al. Antioxidant, immunomodulating, and microbial-modulating activities of the sustainable and ecofriendly Spirulina. Oxid Med Cell Longev 2017:3247528. . 2017. Link

Study (Oxid Med Cell Longev) on the antioxidant, immunomodulating and microbial-modulating activities of Spirulina.

[2183] Merchant RE et al. Nutritional supplementation with Chlorella pyrenoidosa for patients with fibromyalgia syndrome: a double-blind, placebo-controlled, crossover trial. Phytother Res 2000;14(3):167–173. . 2000. Link

Fibromyalgia syndrome is a common, chronic musculoskeletal disorder of unknown aetiology. While available therapy is often disappointing, most patients can be helped with a combination of medication, exercise and maintenance of a regular sleep schedule. The objective of the present study was to determine if adding nutritional supplements derived from the unicellular green alga, Chlorella pyrenoidosa, produced any improvements in the clinical and functional status in patients with moderately severe symptoms of fibromyalgia syndrome. Eligible patients had 2+ palpable tenderness at 11 or more of 18 defined tender points and had a tender point index (TPI) of at least 22. Each day for 2 months, participants consumed two commercially available Chlorella-based products, 10 g of 'Sun Chlorella' tablets and 100 mL of liquid 'Wakasa Gold'. Any amelioration of symptoms was validated and quantified using semi-objective and subjective outcome measures systematically administered at clinic visits on days 0, 30 and 60 of the diet therapy.

[2184] Nakano S et al. Chlorella pyrenoidosa supplementation reduces the risk of anemia, proteinuria and edema in pregnant women. Plant Foods Hum Nutr 2010;65(1):25–30. . 2010. Link

Pregnancy anemia and pregnancy-induced hypertension (PIH) are common and potentially dangerous disorder in human pregnancy, and nutritional status of pregnant women is one of the leading causes. Chlorella contains large quantities of folate, vitamin B-12 and iron, and can help improve anemia and hypertensive disorder. Our objective was to investigate the preventive effects of Chlorella supplement on pregnancy anemia and PIH in Japanese pregnant women. A total of 70 pregnant women were placed into the control group (n = 38) or the Chlorella group (n = 32). The subjects in the Chlorella group were supplemented daily from 12th-18th wk of gestation until delivery with 6 g of Chlorella supplement. The proportion of anemic (hemoglobin level < 11 g/dL) subjects in the Chlorella group were significantly lower compared with the control group at the second and third trimesters.

[2185] Uchikawa T et al. The enhanced elimination of tissue methylmercury in Parachlorella beijerinckii–fed mice. J Toxicol Sci 2010;35(1):101–105. . 2010. Link

To investigate the influence of Chlorella (Parachlorella beijerinckii) on the excretion and tissue accumulation of methylmercury (MeHg), we orally administered 5 mg/kg of MeHg chloride (4 mg Hg/kg) to female C57BL/6N mice (aged 10 weeks). The mice were housed in metabolism cages to collect urine and feces for 3 weeks with diets containing 0\%, 5\%, or 10\% P. beijerinckii powder (BP) in a basal diet (CE-2). The lowered blood Hg levels in the 5\% and 10\% BP groups became significant compared to those of the control group (0\% BP) as early as day 7. During the 21 days of testing, significant increases in the cumulative Hg eliminations into urine (5\% BP) and feces (5\% and 10\% BP) were found in the BP groups. Twenty-one days after administration, the organ Hg levels in both BP groups tended to decrease compared to that of the control group. The reduction of Hg levels in the kidney and brain were significant, whereas that in the liver was not.

[2186] Watanabe F et al. Characterization of a vitamin B12 compound from edible cyanobacteria and microalgae. J Agric Food Chem 2002;50(20):5780–5784. . 2002. Link

Research article characterizing a vitamin B12 compound from edible cyanobacteria and microalgae.

[2187] Bito T et al. Bioactive compounds of edible purple laver Porphyra sp. (Nori). J Agric Food Chem 2017;65(46):10685–10692 (összehasonlító B12-adatok). . 2017. Link

Porphyra sp. (nori) is widely cultivated as an important marine crop. Dried nori contains numerous nutrients, including vitamin B12, which is the only vitamin absent from plant-derived food sources. Vegetarian diets are low in iron and vitamin B12; depletion of both causes severe anemia. Nori also contains large amounts of iron compared with other plant-derived foods and eicosapentaenoic acid, which is an important fatty acid found in fish oils. In nori, there are also many bioactive compounds that exhibit various pharmacological activities, such as immunomodulation, anticancer, antihyperlipidemic, and antioxidative activities, indicating that consumption of nori is beneficial to human health. However, Porphyra sp. contains toxic metals (arsenic and cadmiun) and/or amphipod allergens, the levels of which vary significantly among nori products.

[2188] Panahi Y et al. Investigation of the effects of Chlorella vulgaris as an adjunctive therapy for dyslipidemia: results of a randomized open-label clinical trial. Nutr Diet 2012;69(1):13–19. . 2012. Link

Randomized open-label clinical trial investigating Chlorella vulgaris as an adjunctive therapy for dyslipidemia.

[2189] EFSA. Safety of Chlorella vulgaris as a novel food. EFSA Journal 2017. . 2017.

EFSA scientific opinion on the safety of Chlorella vulgaris as a novel food.

[2190] Bito T et al. Potential of Chlorella as a dietary source of vitamin B12. Nutrients 2020;12(9):2524. . 2020. Link

Study (Nutrients) on the potential of Chlorella as a dietary source of vitamin B12.

[2191] Hehemann JH et al. Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature 2010;464(7290):908–912. . 2010. Link

Research paper on the transfer of carbohydrate-active enzymes from marine bacteria to the Japanese gut microbiota.

[2192] Bito T et al. Bioactive compounds of edible purple laver Porphyra sp. (Nori). J Agric Food Chem 2017;65(46):10685–10692. . 2017. Link

[2193] Watanabe F et al. Pseudovitamin B(12) is the predominant cobamide of an algal health food, spirulina tablets. J Agric Food Chem 1999;47(11):4736–4741 (összehasonlító nori-adatok). . 1999. Link

[2194] Croft MT et al. Algae acquire vitamin B12 through a symbiotic relationship with bacteria. Nature 2005;438(7064):90–93. . 2005. Link

Research article on how algae acquire vitamin B12 through a symbiotic relationship with bacteria.

[2195] Takachi R et al. Consumption of sodium and salted foods in relation to cancer and cardiovascular disease: the Japan Public Health Center-based Prospective Study. Am J Clin Nutr 2010;91(2):456–464. . 2010. Link

BACKGROUND: Although the influence of salt, per se, on the risk of cancer or cardiovascular disease (CVD) might differ from that of salt-preserved foods, few studies have simultaneously examined the effects of sodium and salted foods on the risk of either cancer or CVD. OBJECTIVE: We simultaneously examined associations between sodium and salted food consumption and the risk of cancer and CVD. DESIGN: During 1995-1998, a validated food-frequency questionnaire was administered to 77,500 men and women aged 45-74 y. During up to 598,763 person-years of follow-up until the end of 2004, 4476 cases of cancer and 2066 cases of CVD were identified. RESULTS: Higher consumption of sodium was associated with a higher risk of CVD but not with the risk of total cancer: multivariate hazard ratios for the highest compared with lowest quintiles of intake were 1.19 (95\% CI: 1.01, 1.40; P for trend: 0.06) for CVD and 1.04 (95\% CI: 0.93, 1.16; P for trend: 0.63) for total cancer. Higher consumption of salted fish roe was associated with higher risk of total cancer, and higher consumption of cooking and table salt was associated with higher risk of CVD.

[2196] Murata M, Nakazoe J. Production and use of marine algae in Japan. JARQ 2001;35(4):281–290. . 2001. Link

Research paper on the production and use of marine algae in Japan.

[2197] Drew K. Conchocelis-phase in the life-history of Porphyra umbilicalis. Nature 1949;164:748–749. . 1949. Link

Drew K's classic paper on the Conchocelis-phase in the life-history of Porphyra umbilicalis.

[2198] Cian RE et al. Proteins and carbohydrates from red seaweeds: evidence for beneficial effects on gut function and microbiota. Mar Drugs 2015;13(8):5358–5383. . 2015. Link

Review article (Mar Drugs) on proteins and carbohydrates from red seaweeds and evidence for their beneficial effects on gut function and microbiota.

[2199] Galland-Irmouli AV et al. Nutritional value of proteins from edible seaweed Palmaria palmata (Dulse). J Nutr Biochem 1999;10(6):353–359. . 1999. Link

Research article on the nutritional value of proteins from the edible seaweed Palmaria palmata (Dulse).

[2200] Furuta T et al. Antihypertensive effects of seaweed-derived ACE-inhibitory peptides. Mar Drugs 2016;14(2):32. . 2016. Link

Study (Mar Drugs) on the antihypertensive effects of seaweed-derived ACE-inhibitory peptides.

[2201] Mouritsen OG et al. The science of taste: dulse and the umami of the seaweed. Flavour 2013;2:4. . 2013.

Research paper on the science of taste, dulse, and the umami of seaweed.

[2202] Pereira L. Edible Seaweeds of the World. CRC Press 2016. . 2016.

Pereira L's reference book on the Edible Seaweeds of the World.

[2203] MacArtain P et al. Nutritional value of edible seaweeds. Nutr Rev 2007;65(12):535–543. . 2007. Link

This article presents information on the nutritional aspects of seaweeds in terms of fiber, mineral content, fats and lipids, vitamin contents, and components that have a confirmed and investigated nutritional effect. The nutrient levels of seaweeds are also shown in comparison to currently applicable reference nutrient intakes or guideline daily amounts of nutrients and are contrasted with terrestrial foodstuffs with respect to selected nutrients. For the purpose of comparison, a sample serving size of 8 g dry weight of seaweed is used to illustrate the potential contribution of seaweeds to the diet.

[2204] Cofrades S et al. Nutritional and antioxidant properties of different brown and red Spanish edible seaweeds. Food Sci Technol Int 2010;16(5):361–370. . 2010. Link

Experimental study of the nutritional and antioxidant properties of three Spanish edible seaweeds: two brown (Himanthalia elongata, Undaria pinnatifida) and one red (Porphyra umbilicalis). Total dietary fibre and ash predominated in the brown seaweeds, while fibre and protein predominated in the red one; lipid content was low in all but polyunsaturated fatty acid proportions were high. All three contained essential amino acids at levels comparable to FAO/WHO requirements, and the brown seaweeds were richer in minerals (K, Na, Ca, Mg).

[2205] EFSA. Scientific opinion on the tolerable upper intake level of iodine. EFSA Journal 2014. . 2014. Link

EFSA scientific opinion on the tolerable upper intake level of iodine.

[2207] Food Standards Australia New Zealand (FSANZ). Inorganic arsenic in seaweed (hijiki). 2001, updated 2014. . 2001. Link

Food Standards Australia New Zealand (FSANZ) statement on inorganic arsenic in seaweed (hijiki).

[2208] UK Food Standards Agency. Arsenic in seaweed: hijiki advisory. 2004, updated 2010. . 2004. Link

UK Food Standards Agency hijiki advisory on arsenic in seaweed.

[2209] Hanaoka K et al. Arsenic in the prepared edible brown alga hijiki, Hizikia fusiforme. Appl Organomet Chem 2001;15(7):561–565. . 2001. Link

Research article on arsenic in the prepared edible brown alga hijiki, Hizikia fusiforme.

[2210] Rose M et al. Arsenic in seaweed — forms, concentration and dietary exposure. Food Chem Toxicol 2007;45(7):1263–1267. . 2007. Link

This study has measured the content of total and inorganic forms of arsenic in seaweed available on retail sale for consumption, to provide data for dietary exposure estimates and to support advice to consumers. A total of 31 samples covering five varieties of seaweed were collected from various retail outlets across London and the internet. All of the samples were purchased as dried product. For four of the five varieties, soaking was advised prior to consumption. The recommended method of preparation for each individual sample was followed, and total and inorganic arsenic were analysed both before and after preparation. The arsenic remaining in the water used for soaking was also measured.

[2211] IARC. Arsenic, metals, fibres, and dusts. IARC Monogr Eval Carcinog Risks Hum 2012;100C:11–465. . 2012. Link

IARC monograph on arsenic, metals, fibres, and dusts in the series evaluating carcinogenic risks to humans.

[2212] Almela C et al. Total arsenic, inorganic arsenic, lead and cadmium contents in edible seaweed sold in Spain. Food Chem Toxicol 2006;44(11):1901–1908. . 2006. Link

Total arsenic, inorganic arsenic, lead and cadmium contents were determined in 112 samples of seaweed preparations sold in Spain (seaweed packed in plastic or cardboard box, seaweed in the form of tablets and concentrates, foods containing seaweed, and canned seaweed). The concentration ranges found, expressed in mg/kg, dry weight, were: total As (0.031-149), inorganic As (<0.014-117), Pb (<0.050-12.1) and Cd (<0.003-3.55). For all the contaminants there were failures to comply with legislated values. In particular, all the samples of Hizikia fusiforme exceeded the inorganic As limit established in some countries, and a considerable number of species exceeded the Cd limit set by international regulations. With respect to food safety, consumption of 3 g/day of the samples analysed could represent up to 15\% of the respective Tolerable Daily Intakes (TDI) established by the WHO. The situation is especially alarming for intake of inorganic As from H. fusiforme, which can be three times the TDI established.

[2213] Tokyo Metropolitan Government. Public health advisory on hijiki consumption. 2004 (japán nyelvű). . 2004.

Tokyo Metropolitan Government public health advisory on hijiki consumption (in Japanese).

[2214] Hong Kong Centre for Food Safety. Inorganic arsenic in hijiki seaweed. Risk Assessment Studies 2010;42. . 2010. Link

Hong Kong Centre for Food Safety risk assessment study on inorganic arsenic in hijiki seaweed.

[2215] Kushi M, Jack A. The Macrobiotic Path to Total Health (2003) — modern makrobiotikus iránymutatás arame preferenciával. . 2003.

Kushi M and Jack A's book (The Macrobiotic Path to Total Health), modern macrobiotic guidance with an arame preference.

[2216] EFSA EFSA Journal. 2018. Re-evaluation of carrageenan (E407) and processed Eucheuma seaweed (E407a) as food additives. 2018. Link

EFSA scientific opinion on the re-evaluation of carrageenan (E407) and processed Eucheuma seaweed (E407a) as food additives.

[2217] EFSA Panel on Food Additives EFSA Journal. EFSA Panel on Food Additives EFSA Journal. 2017. Re-evaluation of carrageenan in infant formula. 2017. Link

Scientific opinion of the EFSA Panel on Food Additives on the re-evaluation of carrageenan as a food additive, with particular attention to its use in infant formula. Based on the available data, the Panel regarded the group acceptable daily intake for carrageenan as temporary and called for the database to be improved to address uncertainties, including those around infant exposure. (The exact EFSA Journal identifier could not be unambiguously confirmed in the sources.)

[2218] . JECFA (Joint FAO/WHO Expert Committee on Food Additives) 2014. 79th meeting report — carrageenan safety evaluation. 2014. Link

Report of the 79th meeting (2014) of the Joint FAO/WHO Expert Committee on Food Additives (JECFA) on the safety evaluation of carrageenan, focused on its use in infant formula. After reviewing a newer piglet study modelling human infants, JECFA concluded that the use of carrageenan up to 1000 mg/L in infant formula and formula for special medical purposes is not of concern, as it did not cause adverse effects on the gut or immune parameters.

[2219] Tobacman JK Environ Health Perspect. 2001;109(10):983–994. Review of harmful gastrointestinal effects of carrageenan in animal experiments. 2001. Link

Review of the harmful gastrointestinal effects of carrageenan in animal experiments.

[2220] Bhattacharyya S, et al. Nutr Healthy Aging. 2017;4(2):181–192. A randomized trial of the effects of the no-carrageenan diet on ulcerative colitis disease activity. 2017. Link

BACKGROUND: Carrageenan is a very common food additive in Western diets, but predictably causes inflammation in thousands of cell-based and animal experiments. OBJECTIVE: To assess the impact of carrageenan exposure on the interval to relapse in patients with ulcerative colitis in remission. METHODS: A randomized, double-blind, placebo-controlled, multicenter, clinical trial was conducted to assess if patients with ulcerative colitis in remission would have a longer interval to relapse if they followed a diet with no carrageenan. All participants were instructed in the no-carrageenan diet and were randomized to either placebo capsules or carrageenan-containing capsules. The carrageenan in the capsules was less than the average daily carrageenan intake from the diet. Relapse was defined as an increase of two or more points on the Simple Clinical Colitis Activity Index (SCCAI) and intensification of treatment for ulcerative colitis.

[2221] Liu J, et al. Food Funct. 2015. Pilot study of Chondrus crispus on LDL and antioxidant capacity. 2015.

Pilot study (Food Funct., 2015) examining the effect of Chondrus crispus (Irish moss) on LDL cholesterol and antioxidant capacity.

[2222] Pereira L Algae. Pereira L Algae. 2018. Therapeutic and nutritional uses of algae. 2018.

Review by Pereira L. (Algae, 2018) on the therapeutic and nutritional uses of algae.

[2223] McKim JM Toxicology. 2014. Food additive carrageenan: Part I — A critical review of carrageenan in vitro studies. 2014. Link

Carrageenan (CGN) has been used as a safe food additive for several decades. Confusion over nomenclature, basic CGN chemistry, type of CGN tested, interspecies biology, and misinterpretation of both in vivo and in vitro data has resulted in the dissemination of incorrect information regarding the human safety of CGN. The issue is exacerbated when mechanistic data obtained from in vitro experiments are directly translated to human hazard and used for risk assessment. This can lead to information that is taken out of experimental context and reported as a definitive effect in humans. In recent years, the use of cell-based models has increased and their ability to provide key information regarding chemical or drug safety is well established. In many instances, these new alternative approaches have started to replace the need to use animals altogether.

[2224] Du Pré P, et al. Mar Drugs. 2019. In vitro fermentation of carrageenan fractions by gut microbiota. 2019.

In vitro study (Mar Drugs, 2019) on the fermentation of carrageenan fractions by gut microbiota.

[2225] . Mouritsen OG University of Chicago Press, 2013. Seaweeds: Edible, Available, Sustainable. 2013.

Book by Mouritsen OG (University of Chicago Press, 2013) on edible seaweeds: availability and sustainability.

[2226] . Salisbury W 1849. Botanical Treatment of Irish Moss.

Early work by Salisbury W. (1849) on the botanical treatment of Irish moss.

[2227] EMA/HMPC 2018 (rev. EMA/HMPC 2018 (rev. 1). Community herbal monograph on Curcuma longa L., rhizoma. 2018.

EMA/HMPC community herbal monograph (2018, rev. 1) on Curcuma longa L., rhizoma (turmeric rhizome).

[2228] Shoba G et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers1998;64(4):353–356. Planta Medica. Link

[2229] Cuomo J et al. Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation2011;74(4):664–669. J Nat Prod. Link

The relative absorption of a standardized curcuminoid mixture and its corresponding lecithin formulation (Meriva) was investigated in a randomized, double-blind, crossover human study. Clinically validated dosages were used for both products, and plasma levels of all three major curcuminoids [curcumin (1a), demethoxycurcumin (1b), and bisdemethoxycurcumin (1c)] were evaluated. Total curcuminoid absorption was about 29-fold higher for Meriva than for its corresponding unformulated curcuminoid mixture, but only phase-2 metabolites could be detected, and plasma concentrations were still significantly lower than those required for the inhibition of most anti-inflammatory targets of curcumin. Remarkably, phospholipid formulation increased the absorption of demethoxylated curcuminoids much more than that of curcumin (1a), with significant differences in plasma curcuminoid profile between Meriva and its corresponding unformulated curcuminoid mixture. Thus, the major plasma curcuminoid after administration of Meriva was not curcumin (1a), but demethoxycurcumin (1b), a more potent analogue in many in vitro anti-inflammatory assays. The improved absorption, and possibly also a better plasma curcuminoid profile, might underlie the clinical efficacy of Meriva at doses significantly lower than unformulated curcuminoid mixtures.

[2230] Daily JW et al. Efficacy of turmeric extracts and curcumin for alleviating the symptoms of joint arthritis: a systematic review and meta-analysis2016;19(8):717–729. J Med Food. Link

Systematic review and meta-analysis (J Med Food) on the efficacy of turmeric extracts and curcumin for alleviating joint arthritis symptoms.

[2231] Hanai H et al. Curcumin maintenance therapy for ulcerative colitis2006;4(12):1502–1506. Clin Gastroenterol Hepatol. Link

BACKGROUND \& AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators.

[2232] Ebrahimzadeh A et al. Curcumin in NAFLD: meta-analysis of randomized controlled trials 2025. Phytother Res. 2025.

Meta-analysis of randomized controlled trials (Phytother Res, 2025) on the effect of curcumin in non-alcoholic fatty liver disease (NAFLD).

[2233] Italian National Institute of Health (ISS). Hepatitis from curcumin/piperine supplements — pharmacovigilance report 2020. . 2020.

Pharmacovigilance report by the Italian National Institute of Health (ISS, 2020) on hepatitis cases associated with curcumin/piperine supplements.

[2234] Scazzocchio B et al. Interaction between gut microbiota and curcumin: a new key of understanding for the health effects of curcumin2020;12(9):2499. Nutrients. Link

Review (Nutrients, 2020) on the interaction between gut microbiota and curcumin as a key to understanding curcumin's health effects.

[2235] EFSA. Refined exposure assessment for curcumin (E100) 2014. EFSA Journal. 2014.

EFSA refined exposure assessment (EFSA Journal, 2014) for curcumin (E100) as a food additive.

[2236] EMA/HMPC 2024 (rev. EMA/HMPC 2024 (rev. 1). European Union herbal monograph on Zingiber officinale Roscoe, rhizoma. 2024.

EMA/HMPC European Union herbal monograph (2024, rev. 1) on Zingiber officinale Roscoe, rhizoma (ginger rhizome).

[2237] Viljoen E et al. A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting2014;13:20. Nutr J. Link

Systematic review and meta-analysis (Nutr J, 2014) on the effect and safety of ginger in treating pregnancy-associated nausea and vomiting.

[2238] Wu KL et al. Effects of ginger on gastric emptying and motility in healthy humans2008;20(5):436–440. Eur J Gastroenterol Hepatol. Link

OBJECTIVE: Ginger has been reported to improve upper gastrointestinal symptoms. Little information about the effects of ginger on gastric motor function, exists, however. Our aim was to investigate the effects of ginger on gastric emptying, antral motility, proximal gastric dimensions, and postprandial symptoms. METHODS: Twenty-four healthy volunteers were studied twice in a randomized double-blind manner. After an 8 h fast, the volunteers ingested three ginger capsules (total 1200 mg) or placebo, followed after 1 h by 500 ml low-nutrient soup. Antral area, fundus area and diameter, and the frequency of antral contractions were measured using ultrasound at frequent intervals over 90 min, and the gastric half-emptying time was calculated from the change in antral area.

[2239] Bossi P et al. A randomized, double-blind, placebo-controlled, multicenter study of a ginger extract in the management of chemotherapy-induced nausea2017;28(10):2547–2551. Ann Oncol. Link

Randomized, double-blind, placebo-controlled, multicenter study (Ann Oncol) on a ginger extract in the management of chemotherapy-induced nausea.

[2240] . Royal College of Obstetricians and Gynaecologists2016. Green-top Guideline No. 69: The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum. Link

Royal College of Obstetricians and Gynaecologists guideline (Green-top Guideline No. 69, 2016) on the management of nausea, vomiting of pregnancy and hyperemesis gravidarum.

[2241] Bartels EM et al. Efficacy and safety of ginger in osteoarthritis patients: a meta-analysis2015;23(1):13–21. Osteoarthritis Cartilage. Link

The aim of this study was to assess the clinical efficacy and safety of oral ginger for symptomatic treatment of osteoarthritis (OA) by carrying out a systematic literature search followed by meta-analyses on selected studies. Inclusion criteria were randomized controlled trials (RCTs) comparing oral ginger treatment with placebo in OA patients aged >18 years. Outcomes were reduction in pain and reduction in disability. Harm was assessed as withdrawals due to adverse events. The efficacy effect size was estimated using Hedges' standardized mean difference (SMD), and safety by risk ratio (RR). Standard random-effects meta-analysis was used, and inconsistency was evaluated by the I-squared index (I(2)).

[2242] Lu Q et al. Ginger intake alters the gut microbiota: a randomized controlled trial 2024. Sci Rep. 2024.

Randomized controlled trial (Sci Rep, 2024) reporting that ginger intake alters the gut microbiota.

[2243] Mao QQ et al. Bioactive compounds and bioactivities of ginger (Zingiber officinale)2019;8(6):185. Foods. 2019. Link

Ginger (Zingiber officinale Roscoe) is a common and widely used spice. It is rich in various chemical constituents, including phenolic compounds, terpenes, polysaccharides, lipids, organic acids, and raw fibers. The health benefits of ginger are mainly attributed to its phenolic compounds, such as gingerols and shogaols. Accumulated investigations have demonstrated that ginger possesses multiple biological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, neuroprotective, cardiovascular protective, respiratory protective, antiobesity, antidiabetic, antinausea, and antiemetic activities. In this review, we summarize current knowledge about the bioactive compounds and bioactivities of ginger, and the mechanisms of action are also discussed. We hope that this updated review paper will attract more attention to ginger and its further applications, including its potential to be developed into functional foods or nutraceuticals for the prevention and management of chronic diseases.

[2244] EFSA Panel on Food Additives. Coumarin in flavourings and other food ingredients with flavouring properties 2008;6(10):793. EFSA Journal. 2008. Link

Scientific opinion of the EFSA AFC Panel on coumarin in flavourings and other food ingredients with flavouring properties. Based on the NOAEL for liver toxicity in the most sensitive animal species (a two-year dog study, 10 mg/kg bw/day) and a safety factor of 100, the Panel established a tolerable daily intake (TDI) of 0–0.1 mg coumarin/kg body weight.

[2245] Akilen R et al. Cinnamon in glycaemic control: systematic review and meta-analysis2012;31(5):609–615. Clin Nutr. Link

BACKGROUND \& AIMS: Cinnamon seems to be highly bioactive, appearing to mimic the effect of insulin through increased glucose uptake in adipocytes and skeletal muscles. This systematic review and Meta analysis examined the effect of cinnamon on glycaemic control in patients with Type 2 Diabetes mellitus. METHODS: A systematic literature search was conducted from the earliest possible date through to 01 August 2011. Search terms included free text terms, MeSH and Medline medical index terms such as: "cinnamon", "cinnamomum", "cinnamomum cassia", "cinnamomum zeylanicum", "type 2 diabetes mellitus". Each was crossed with the term "diabetes mellitus". In addition, references of key articles were hand searched.

[2246] Allen RW et al. Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis2013;11(5):452–459. Ann Fam Med. Link

An updated systematic review and meta-analysis examining the use of cinnamon in type 2 diabetes, published in Ann Fam Med. It pools clinical trial evidence on cinnamon and glucose control.

[2247] Khan A et al. Cinnamon improves glucose and lipids of people with type 2 diabetes2003;26(12):3215–3218. Diabetes Care. Link

OBJECTIVE: The objective of this study was to determine whether cinnamon improves blood glucose, triglyceride, total cholesterol, HDL cholesterol, and LDL cholesterol levels in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 60 people with type 2 diabetes, 30 men and 30 women aged 52.2 +/- 6.32 years, were divided randomly into six groups. Groups 1, 2, and 3 consumed 1, 3, or 6 g of cinnamon daily, respectively, and groups 4, 5, and 6 were given placebo capsules corresponding to the number of capsules consumed for the three levels of cinnamon. The cinnamon was consumed for 40 days followed by a 20-day washout period. RESULTS: After 40 days, all three levels of cinnamon reduced the mean fasting serum glucose (18-29\%), triglyceride (23-30\%), LDL cholesterol (7-27\%), and total cholesterol (12-26\%) levels; no significant changes were noted in the placebo groups. Changes in HDL cholesterol were not significant.

[2248] BfR (German Federal Institute for Risk Assessment). High daily intakes of cinnamon: health risk cannot be ruled out 2006. BfR Opinion. 2006.

Opinion by the German BfR (Federal Institute for Risk Assessment, 2006) noting that a health risk from high daily cinnamon intake cannot be ruled out.

[2249] Ranasinghe P et al. Medicinal properties of „true" cinnamon (Cinnamomum zeylanicum): a systematic review2013;13:275. BMC Complement Altern Med. Link

A systematic review of the medicinal properties of "true" cinnamon (Cinnamomum zeylanicum), published in BMC Complement Altern Med. It summarizes the purported health effects attributed to this cinnamon species.

[2250] . EMA/HMPC 2011. European Union herbal monograph on Cinnamomum verum. 2011.

EMA/HMPC European Union herbal monograph (2011) on Cinnamomum verum (true cinnamon).

[2251] Lu T et al. Cinnamon polyphenol extract and gut microbiota modulation 2021. Food Funct. 2021.

Study (Food Funct, 2021) on cinnamon polyphenol extract and gut microbiota modulation.

[2253] Srinivasan K. Black pepper and its pungent principle piperine: a review of diverse physiological effects2007;47(8):735–748. Crit Rev Food Sci Nutr. Link

Black pepper (Piper nigrum) is one of the most widely used among spices. It is valued for its distinct biting quality attributed to the alkaloid, piperine. Black pepper is used not only in human dietaries but also for a variety of other purposes such as medicinal, as a preservative, and in perfumery. Many physiological effects of black pepper, its extracts, or its major active principle, piperine, have been reported in recent decades. Dietary piperine, by favorably stimulating the digestive enzymes of pancreas, enhances the digestive capacity and significantly reduces the gastrointestinal food transit time. Piperine has been demonstrated in in vitro studies to protect against oxidative damage by inhibiting or quenching free radicals and reactive oxygen species.

[2254] Bhardwaj RK et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A42002;302(2):645–650. J Pharmacol Exp Ther. Link

Study (J Pharmacol Exp Ther, 2002) showing that piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4.

[2255] Atal CK et al. Biochemical basis of enhanced drug bioavailability by piperine: target organs and drug-metabolizing enzymes 1985;232(1):258–262. J Pharmacol Exp Ther. 1985. Link

In vitro and in vivo rat studies on the effect of piperine — the major active component of black and long pepper — on drug metabolism, explaining its drug-bioavailability-enhancing property. Piperine dose-dependently inhibited several hepatic drug-metabolizing reactions (e.g., arylhydrocarbon hydroxylation, ethylmorphine-N-demethylation, 7-ethoxycoumarin-O-deethylation, glucuronidation). The authors concluded that piperine is a nonspecific inhibitor of drug metabolism showing little discrimination between cytochrome P-450 forms.

[2256] Damanhouri ZA et al. A review on therapeutic potential of Piper nigrum 2014;3:161. Med Aromat Plants. 2014.

Review (Med Aromat Plants, 2014) on the therapeutic potential of Piper nigrum (black pepper).

[2257] Wang Y et al. Piperine and gut microbiota — metabolic regulation in obesity model 2020. Food Funct. 2020.

Study (Food Funct, 2020) on piperine and gut microbiota and metabolic regulation in an obesity model.

[2258] EMA/HMPC. Piperine — herbal substance overview.

EMA/HMPC herbal substance overview of piperine.

[2259] . EMA/HMPC 2013. European Union herbal monograph on Armoracia rusticana, radix. 2013.

EMA/HMPC European Union herbal monograph (2013) on Armoracia rusticana, radix (horseradish root).

[2260] Kommission E. Monograph Armoraciae rusticanae radix 1988. Bundesanzeiger. 1988.

German Kommission E monograph (Bundesanzeiger, 1988) on Armoraciae rusticanae radix (horseradish root).

[2261] Albrecht U et al. A randomised, double-blind, placebo-controlled trial of a herbal medicinal product containing Tropaeoli majoris herba and Armoraciae rusticanae radix for the prophylactic treatment of patients with chronically recurrent lower urinary tract infections2007;23(10):2415–2422. Curr Med Res Opin. Link

OBJECTIVES: The aim of this study was to verify the efficacy and safety of a herbal medicinal product containing Tropaeoli majoris herba and Armoraciae rusticanae radix in the prophylactic treatment of chronically recurrent urinary tract infections (UTIs), and to test whether the medicinal product decreases the incidence of relapses over the study period. METHODS: A total of 219 adults aged between 18 and 75 years were screened and 174 patients enrolled. Of these 174 patients, a group of 45 patients were screening failures. Patients were randomised to receive either the study drug or placebo twice daily for 90 days. A UTI is confirmed by defined symptoms together with a laboratory result. The diagnosis of a new episode of a recurrent UTI included urine analysis from a central laboratory.

[2262] Goos KH et al. Efficacy and safety profile of a herbal drug containing nasturtium herb and horseradish root in acute sinusitis, acute bronchitis and acute urinary tract infection in comparison with other treatments 2006;56(3):249–257. Arzneimittelforschung. 2006.

Study (Arzneimittelforschung, 2006) on the efficacy and safety of a herbal drug containing nasturtium herb and horseradish root in acute sinusitis, acute bronchitis and acute urinary tract infection, compared with other treatments.

[2263] Conrad A et al. In vitro study to evaluate the antibacterial activity of a combination of the haulm of nasturtium (Tropaeoli majoris herba) and the roots of horseradish 2013. Drug Res. 2013.

In vitro study (Drug Res, 2013) evaluating the antibacterial activity of a combination of nasturtium (Tropaeoli majoris herba) and horseradish roots.

[2264] Agneta R et al. Horseradish (Armoracia rusticana), a neglected medical and condiment species 2014. Med Aromat Plants. 2014.

Review (Med Aromat Plants, 2014) on horseradish (Armoracia rusticana) as a neglected medicinal and condiment species.

[2265] Park HW et al. Allyl isothiocyanate from horseradish and Helicobacter pylori 2007. Helicobacter. 2007.

Study (Helicobacter, 2007) on allyl isothiocyanate from horseradish and Helicobacter pylori.

[2266] Caterina MJ et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway1997;389:816–824. Nature. Link

Study by Caterina MJ et al. (Nature, 1997) on the capsaicin receptor as a heat-activated ion channel in the pain pathway.

[2267] Whiting S et al. Capsaicinoids and capsinoids: a potential role for weight management? A systematic review of the evidence2012;59(2):341–348. Appetite. Link

Capsaicinoids are a group of chemicals found in chilli peppers, with bioactive properties. The purpose of this study is to systematically review research investigating the potential benefits capsaicinoid compounds may have in relation to weight management. Medical databases were searched and 90 trials found, 20 of which were selected for inclusion, involving 563 participants. Three main areas of potential benefit for weight management were found: (1) increased energy expenditure; (2) increased lipid oxidation and (3) reduced appetite. Trial duration, dosage and sized varied, though trials were generally of high quality with a low risk of bias. It was observed that consumption of capsaicinoids increases energy expenditure by approximately 50 kcal/day, and that this would produce clinically significant levels of weight loss in 1-2 years.

[2268] Lv J et al. Consumption of spicy foods and total and cause specific mortality: population based cohort study2015;351:h3942. BMJ. Link

A population-based cohort study investigating the association between consumption of spicy foods and total and cause-specific mortality, published in the BMJ. It examines the link between spicy diet and mortality risk.

[2269] Bonaccio M et al. Chili pepper consumption and mortality in Italian adults2019;74(25):3139–3149. J Am Coll Cardiol. Link

BACKGROUND: Chili pepper is a usual part of a traditional Mediterranean diet. Yet epidemiological data on the association between chili pepper intake and mortality risk are scarce, with a lack of studies from Mediterranean populations. OBJECTIVES: This study sought to examine the association between chili pepper consumption and risk of death in a large sample of the adult Italian general population, and to account for biological mediators of the association. METHODS: Longitudinal analysis was performed on 22,811 men and women enrolled in the Moli-sani Study cohort (2005 to 2010). Chili pepper intake was estimated by the EPIC (European Prospective Investigation Into Cancer) Food Frequency Questionnaire and categorized as none/rare consumption, up to 2 times/week, >2 to ≤4 times/week, and >4 times/week. RESULTS: Over a median follow-up of 8.2 years, a total of 1,236 deaths were ascertained.

[2270] Kang C et al. Gut microbiota mediates the protective effects of dietary capsaicin against chronic low-grade inflammation2017. mBio. Link

An experimental study (mBio) showing that the gut microbiota mediates the protective effects of dietary capsaicin against chronic low-grade inflammation. It addresses the capsaicin–microbiota–inflammation axis.

[2271] Szallasi A, Blumberg PM. Vanilloid (capsaicin) receptors and mechanisms 1999;51(2):159–212. Pharmacol Rev. 1999.

Review by Szallasi A and Blumberg PM (Pharmacol Rev, 1999) on vanilloid (capsaicin) receptors and their mechanisms.

[2272] Backonja M et al. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia 2008;7(12):1106–1112. Lancet Neurol. 2008. Link

Randomised, double-blind, 12-week study of the efficacy and safety of a single 60-minute application of the NGX-4010 high-concentration (8%) capsaicin patch in postherpetic neuralgia. In this multicentre, parallel-group trial of 402 patients, participants were randomised to a single application of the capsaicin or a control patch. The study evaluated the analgesic effect of a single patch application for the treatment of postherpetic neuralgia.

[2273] . EMA 2009. Qutenza (capsaicin) — assessment report. 2009.

EMA assessment report (2009) on Qutenza (capsaicin).

[2274] Alqareer A et al. The effect of clove and benzocaine versus placebo as topical anesthetics2006;34(10):747–750. J Dent. Link

OBJECTIVES: The purpose of this study was to examine whether the natural herb clove can replace benzocaine as a topical anesthetic. METHODS: Topical agents were applied to the maxillary canine buccal mucosa of 73 adult volunteers. Four substances were tested in the study: (1) homemade clove gel, (2) benzocaine 20\% gel, (3) placebo that resembles clove and (4) a placebo that resembled benzocaine. After 5 min of material application in a randomized, subject-blinded manner, each participant received two needle sticks. Pain response was registered using a 100 mm visual analogue pain scale. RESULTS: Both clove and benzocaine gels had significantly lower mean pain scores than placebos (p=0.005).

[2275] Cortés-Rojas DF et al. Clove (Syzygium aromaticum): a precious spice2014;4(2):90–96. Asian Pac J Trop Biomed. Link

Clove (Syzygium aromaticum) is one of the most valuable spices that has been used for centuries as food preservative and for many medicinal purposes. Clove is native of Indonesia but nowadays is cultured in several parts of the world including Brazil in the state of Bahia. This plant represents one of the richest source of phenolic compounds such as eugenol, eugenol acetate and gallic acid and posses great potential for pharmaceutical, cosmetic, food and agricultural applications. This review includes the main studies reporting the biological activities of clove and eugenol. The antioxidant and antimicrobial activity of clove is higher than many fruits, vegetables and other spices and should deserve special attention. A new application of clove as larvicidal agent is an interesting strategy to combat dengue which is a serious health problem in Brazil and other tropical countries.

[2276] Pulikottil SJ, Nath S. Potential of clove of Syzygium aromaticum in development of a therapeutic agent for periodontal disease: a review 2015;70(3):108–115. South Afr Dent J. 2015.

Review (South Afr Dent J, 2015) on the potential of clove (Syzygium aromaticum) in developing a therapeutic agent for periodontal disease.

[2277] FDA. Clove oil — pediatric warning notice.

FDA pediatric warning notice on clove oil.

[2278] Chaieb K et al. The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata 2007;21(6):501–506. Phytother Res. 2007. Link

Short review of the chemical composition and biological activity of clove essential oil (Eugenia caryophyllata / Syzygium aromaticum). The main constituents are phenylpropanoids, chiefly eugenol. The authors summarize its antimicrobial, antioxidant, antifungal and antiviral activity (tested pathogens include bacteria, Herpes simplex and hepatitis C virus), as well as anti-inflammatory, cytotoxic, insect-repellent and anaesthetic properties, including new findings against multi-resistant Staphylococcus epidermidis.

[2279] Pramod K et al. Eugenol: a natural compound with versatile pharmacological actions 2010;5(12):1999–2006. Nat Prod Commun. 2010.

Review (Nat Prod Commun, 2010) on eugenol as a natural compound with versatile pharmacological actions.

[2280] Xu JG et al. Clove oil — Helicobacter pylori in vitro 2015. Helicobacter. 2015.

In vitro study (Helicobacter, 2015) on clove oil against Helicobacter pylori.

[2281] Daneshi-Maskooni M et al. Green cardamom supplementation improves serum irisin, glucose indices, and lipid profiles in NAFLD: a double-blind randomized clinical trial2019;19(1):59. BMC Complement Altern Med. Link

BACKGROUND: Despite the reported health effects of cardamom on dyslipidemia, hepatomegaly, and fasting hyperglycemia, no human research has studied its potency in non-alcoholic fatty liver disease (NAFLD) as the hepatic part of metabolic syndrome. Our aim was determining the effects of green cardamom (GC) on serum glucose indices, lipids, and irisin level among overweight or obese NAFLD patients. METHODS: The place of participant recruitment was the polyclinic of the National Iranian Oil Company (NIOC) central hospital in Tehran. Based on the ultrasonography and eligibility criteria, 87 participants were randomly divided into two groups as cardamom (n = 43) or placebo (n = 44). The supplementation was two 500 mg capsules 3 times/day with meals for 3 months. Serum irisin, fasting blood sugar (FBS), insulin (FBI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were measured.

[2282] Aghasi M et al. Beneficial effects of green cardamom on serum SIRT1, glycemic indices and triglyceride levels in patients with type 2 diabetes mellitus 2018;99(8):3933–3940. J Sci Food Agric. 2018. Link

Randomised, double-blind, placebo-controlled clinical trial in 83 overweight/obese patients with type 2 diabetes who received 3 g/day of green cardamom or placebo for 10 weeks. Compared with control, the cardamom group showed significant decreases in HbA1c, insulin, HOMA-IR and triglycerides, and an increase in serum SIRT1. The results indicate a beneficial effect of green cardamom on glycemic indices and lipids in type 2 diabetes.

[2283] Verma SK et al. Effect of green cardamom on blood pressure, lipid profile, oxidative stress and fibrinolytic activity in newly diagnosed Stage I hypertensive patients 2009;46(6):503–506. Indian J Biochem Biophys. 2009.

Study (Indian J Biochem Biophys, 2009) on the effect of green cardamom on blood pressure, lipid profile, oxidative stress and fibrinolytic activity in newly diagnosed Stage I hypertensive patients.

[2284] Padmakumari Amma KP et al. Phytochemical and pharmacological evaluation of small cardamom — review 2010;4(8):134–141. Pharmacogn Rev. 2010.

Phytochemical and pharmacological review (Pharmacogn Rev, 2010) of small cardamom.

[2285] FEMA. Cardamom oil — GRAS evaluation.

FEMA GRAS evaluation of cardamom oil.

[2286] Juergens UR. Anti-inflammatory properties of the monoterpene 1.8-cineole: current evidence for co-medication in inflammatory airway diseases 2014;64(12):638–646. Drug Res. 2014. Link

Review of the anti-inflammatory properties of the monoterpene 1,8-cineole (eucalyptol) and the evidence for its use as co-medication in inflammatory airway diseases (asthma, COPD). The author summarizes the anti-inflammatory and antioxidant mode of action of 1,8-cineole, along with its mucolytic and spasmolytic effects on the airways. More recent clinical trials suggest a beneficial role of 1,8-cineole in preventing COPD exacerbations and improving asthma control.

[2287] Souissi M et al. Anti-bacterial activity of cardamom volatile oil against Streptococcus mutans 2020. Arch Oral Biol. 2020.

Study (Arch Oral Biol, 2020) on the antibacterial activity of cardamom volatile oil against Streptococcus mutans.

[2288] . EMA/HMPC 2014. European Union herbal monograph on Coriandrum sativum L., fructus. 2014.

EMA/HMPC European Union herbal monograph (2014) on Coriandrum sativum L., fructus (coriander fruit).

[2289] Eriksson N et al. A genetic variant near olfactory receptor genes influences cilantro preference2012;1:22. Flavour. Link

Study (Flavour, 2012) on a genetic variant near olfactory receptor genes that influences cilantro preference.

[2290] Eidi M et al. Effect of coriander seed (Coriandrum sativum L.) ethanol extract on insulin release from pancreatic beta cells in streptozotocin-induced diabetic rats 2009;23(3):404–406. Phytother Res. 2009. Link

Experimental study of the effect of coriander seed (Coriandrum sativum L.) ethanol extract on insulin release from pancreatic beta cells in streptozotocin-induced diabetic rats. Intraperitoneal administration of the extract (200 and 250 mg/kg) significantly reduced serum glucose, and the 200 mg/kg dose increased beta-cell activity compared with diabetic controls. The authors concluded that coriander seed extract lowers blood glucose and increases insulin release from pancreatic beta cells.

[2291] Aissaoui A et al. Hypoglycemic and hypolipidemic effects of Coriandrum sativum L. in Meriones shawi rats 2011;137(1):652–661. J Ethnopharmacol. 2011. Link

This study examined the hypoglycemic and hypolipidemic activity of an aqueous extract of coriander (Coriandrum sativum L., Apiaceae) seeds—used in Moroccan traditional diabetes treatment—in normal and obese–hyperglycemic–hyperlipidemic (OHH) Meriones shawi rats after a single oral dose and after 30 days of daily dosing. In OHH rats, sub-chronic administration normalized glycemia and lowered the elevated levels of insulin, insulin resistance, total cholesterol, LDL-cholesterol and triglycerides. The authors concluded that the findings experimentally validate the traditional use of coriander in diabetes.

[2292] Mahleyuddin NN et al. Coriandrum sativum L.: a review on ethnopharmacology, phytochemistry, and cardiovascular benefits 2022;27(1):209. Molecules. 2022.

Review (Molecules, 2022) on the ethnopharmacology, phytochemistry and cardiovascular benefits of Coriandrum sativum L.

[2293] Sahib NG et al. Coriander (Coriandrum sativum L.): a potential source of high-value components for functional foods and nutraceuticals 2013;27(10):1439–1456. Phytother Res. 2013. Link

A review of coriander (Coriandrum sativum L.), a herb of the Apiaceae family valued for both culinary and medicinal uses. The authors describe the plant as a potential source of valuable lipids (rich in petroselinic acid) and essential oil (rich in linalool) obtained from the seeds and aerial parts. A wide array of pharmacological activities is ascribed to its various parts, including antimicrobial, antioxidant, antidiabetic, anxiolytic, antiepileptic, antidepressant, anti-inflammatory, antidyslipidemic and antihypertensive effects, as well as lead-detoxifying potential.

[2294] Wei JN et al. Coriander essential oil — antimicrobial and antifungal activity 2018. Food Control. 2018.

Study (Food Control, 2018) on the antimicrobial and antifungal activity of coriander essential oil.

[2295] Taghizadeh M et al. Effect of the cumin cyminum L. intake on weight loss, metabolic profiles and biochemical markers of oxidative stress in overweight subjects2015;66(2-3):117–124. Ann Nutr Metab. Link

Study (Ann Nutr Metab, 2015) on the effect of Cuminum cyminum (cumin) intake on weight loss, metabolic profiles and biochemical markers of oxidative stress in overweight subjects.

[2296] Zare R et al. Efficacy of cumin in the treatment of irritable bowel syndrome 2016. Compl Ther Clin Pract. 2016.

Study (Compl Ther Clin Pract, 2016) on the efficacy of cumin in the treatment of irritable bowel syndrome (IBS).

[2297] Sahebkar A et al. The effects of cumin (Cuminum cyminum) on glycemic and lipid profile: a systematic review and meta-analysis of clinical trials 2018. Phytother Res. 2018.

Systematic review and meta-analysis of clinical trials (Phytother Res, 2018) on the effects of cumin (Cuminum cyminum) on glycemic and lipid profile.

[2298] Johri RK. Cuminum cyminum and Carum carvi: an update 2011;5(9):63–72. Pharmacogn Rev. 2011. Link

A review of cumin (Cuminum cyminum) and caraway (Carum carvi), the sources of cumin and caraway seeds respectively, which have been used since antiquity for various indications in traditional healing systems across wide geographical areas. The author notes that both seeds are rich sources of essential oils and that their chemical composition and biological activities have been extensively researched. The review reports considerable progress in the experimental validation of their medicinal attributes.

[2299] Singh RP et al. Cumin (Cuminum cyminum L.) seed volatile oil: chemistry and role in health and disease prevention 2017. Nutr Aging. 2017. Link

A book chapter discussing the seed volatile oil of cumin (Cuminum cyminum L.), its chemistry and its role in health and disease prevention. The authors note that cumin's characteristic warm, spicy aroma is due to aldehydes (e.g., cuminaldehyde), with the volatile oil containing components such as γ-terpinene and p-cymene. Cumin is associated with detoxifying, antimicrobial, anti-inflammatory, diuretic, carminative, antioxidant and anticancer effects.

[2300] Ranjan A et al. Cuminaldehyde — mechanisms of action review 2022. Pharmacol Res Mod Chin Med. 2022.

Review (Pharmacol Res Mod Chin Med, 2022) on the mechanisms of action of cuminaldehyde.

[2301] EMA/HMPC. Cumin — herbal substance.

EMA/HMPC herbal substance overview of cumin.

[2302] Sahebkar A et al. The effect of Nigella sativa supplementation on blood pressure: a systematic review and meta-analysis2016;30(11):1736–1745. Phytother Res. Link

Several reports suggest a beneficial effect of Nigella sativa on cardiometabolic risk factors, including blood pressure (BP). However, the magnitude of the BP-lowering effect of N. sativa remains controversial. We aimed to calculate this effect size of N. sativa through a systematic review and meta-analysis of randomized controlled trials (RCTs). PubMed, Cochrane Collaboration Library, and SCOPUS were used as data sources of RCTs published before 30 August 2015 (in English only) comparing N. sativa treatment with placebo or standard treatment. We used random effect models to estimate the difference in BP reductions, I index and χ statistics to measure and test the interstudy heterogeneity. Random effect metaregression models were applied to explore the associations between BP reduction and duration of treatment, dosage of N. sativa, and type of black seed as potential confounders.

[2303] Heshmati J et al. Nigella sativa oil affects glucose metabolism and lipid concentrations in patients with T2DM: a meta-analysis 2015;70:87–93. Food Res Int. 2015. Link

A randomized, double-blind, placebo-controlled clinical trial examining the effect of Nigella sativa (black seed) oil on glucose metabolism and lipid concentrations in type 2 diabetes (T2DM). Seventy-two T2DM patients aged 30–60 were randomized to an intervention (n=36) or placebo (n=36) group, receiving 3 g/day of N. sativa oil or sunflower-oil capsules for 12 weeks. In the intervention group, fasting blood sugar, glycated hemoglobin, triglycerides and LDL-cholesterol improved significantly versus placebo; the authors concluded the oil can improve glycemic status and lipid profile in T2DM patients. (Note: the cited DOI corresponds to the underlying randomized trial; the catalogued title labels it a meta-analysis.)

[2304] Daryabeygi-Khotbehsara R et al. Nigella sativa improves liver function and lipid profile in non-alcoholic fatty liver disease: a meta-analysis 2018;38:81–88. Complement Ther Med. 2018.

Meta-analysis (Complement Ther Med, 2018) on Nigella sativa improving liver function and lipid profile in non-alcoholic fatty liver disease.

[2305] Salem AM et al. Effect of Nigella sativa supplementation on lung function and inflammatory mediators in partly controlled asthma: a randomized controlled trial 2017;37(1):64–71. Ann Saudi Med. 2017. Link

A randomized, placebo-controlled clinical trial examining the effect of Nigella sativa supplementation on lung function and inflammatory mediators in partly controlled asthma, conducted at the asthma and allergy clinic of a university hospital in eastern Saudi Arabia. Patients were divided into three groups: control (placebo, n=24), and NS-1 and NS-2 (1 and 2 g/day of N. sativa, n=26 each) for 3 months alongside maintenance inhaled therapy. Outcome measures included the Asthma Control Test (ACT) score, fractional exhaled nitric oxide (FeNO), pulmonary function parameters, IgE, serum cytokines and frequency of exacerbations.

[2306] Nikakhlagh S et al. Herbal treatment of allergic rhinitis: the use of Nigella sativa 2011;32(5):402–407. Am J Otolaryngol. 2011. Link

A prospective, double-blind clinical trial examining the use of Nigella sativa oil in the treatment of allergic rhinitis. Sixty-six patients with allergic rhinitis (treatment and placebo groups) were exposed to N. sativa oil. The results indicated that N. sativa reduced the presence of nasal mucosal congestion, nasal itching, runny nose, sneezing attacks, turbinate hypertrophy and mucosal pallor during the first two weeks (by day 15).

[2307] . el-Dakhakhny M. Studies on the chemical constitution of Egyptian Nigella sativa L 1963. Planta Med. 1963.

Study by el-Dakhakhny M. (Planta Med, 1963) on the chemical constitution of Egyptian Nigella sativa L.

[2308] Tavakkoli A et al. Review on clinical trials of black seed (Nigella sativa) and its active constituent, thymoquinone 2017;20(3):179–193. J Pharmacopuncture. 2017. Link

A review summarizing the clinical trials of black seed (Nigella sativa) and its main active constituent, thymoquinone (TQ). The authors searched PubMed-Medline, Scopus and Web of Science for randomized controlled trials investigating the therapeutic effects of N. sativa and/or TQ, and reviewed their clinical uses in disease prevention and treatment. The review reports that black seed and TQ possess multiple beneficial effects in various diseases, including inflammatory and autoimmune disorders as well as metabolic syndrome.

[2309] Koshak AE et al. Nigella sativa for the treatment of COVID-19: an open-label randomized controlled clinical trial 2021;61:102769. Complement Ther Med. 2021. Link

An open-label, randomized, controlled clinical trial on the role of Nigella sativa oil (NSO) in the treatment of COVID-19, conducted in Saudi Arabia between May and September 2020 (NCT04401202). The trial enrolled 183 mild COVID-19 outpatients, of whom 91 received 500 mg of N. sativa oil twice daily for 10 days. The results indicated that the oil was associated with a higher rate of symptom resolution and faster recovery in adult patients with mild COVID-19.

[2310] EMA/HMPC 2008 (rev. 2013). European Union herbal monograph on Foeniculum vulgare Miller subsp. vulgare var. dulce. 2008.

EMA/HMPC European Union herbal monograph (2008, rev. 2013) on Foeniculum vulgare Miller subsp. vulgare var. dulce (sweet fennel).

[2311] Alexandrovich I et al. The effect of fennel (Foeniculum vulgare) seed oil emulsion in infantile colic: a randomized placebo-controlled study2003;9(4):58–61. Altern Ther Health Med. Link

CONTEXT: Despite its benign, natural course, colic is a significant problem in infants and imparts a psychological, emotional, and physical burden to parents. Dicyclomine hydrochloride is the only pharmacological treatment for infantile colic that has been consistently effective. Unfortunately, 5\% of infants treated with dicyclomine hydrochloride develop serious side effects, including death. Fennel seed oil has been shown to reduce intestinal spasms and increase motility of the small intestine. However, there have not been any clinical studies of its effectiveness. OBJECTIVES: To determine the effectiveness of fennel seed oil emulsion in infantile colic.

[2312] Picon PD et al. Randomized clinical trial of a phytotherapic compound containing Pimpinella anisum, Foeniculum vulgare, Sambucus nigra, and Cassia augustifolia for chronic constipation 2010;10:17. BMC Complement Altern Med. 2010. Link

A randomized, crossover, placebo-controlled, single-blind clinical trial of a phytotherapic compound widely used in Brazil—containing Pimpinella anisum, Foeniculum vulgare, Sambucus nigra and Cassia angustifolia—for chronic constipation. Twenty patients with chronic constipation participated: one half received the compound for 5 days and the other placebo, with a 9-day washout followed by reverse treatment. With active treatment, mean colonic transit time was shorter (15.7 h vs. 42.3 h with placebo) and the number of daily evacuations increased; the authors concluded the compound has laxative efficacy and is a safe alternative for treating constipation.

[2313] EFSA. Compendium of botanicals reported to contain naturally occurring substances of possible concern for human health (estragole) 2012. EFSA Journal. 2012. Link

An EFSA (European Food Safety Authority) scientific report: the Compendium of botanicals listing plants containing naturally occurring substances of possible concern for human health when used in food and food supplements. The compendium aims to assist risk assessors in identifying compounds of concern during safety assessment, flagging potentially hazardous plants, plant parts or compounds naturally present in the listed botanicals. Estragole-containing species (e.g., Foeniculum vulgare) are among the botanicals flagged for substances of concern.

[2314] Badgujar SB et al. Foeniculum vulgare Mill: a review of its botany, phytochemistry, pharmacology, contemporary application, and toxicology 2014;2014:842674. Biomed Res Int. 2014. Link

A review of the botany, phytochemistry, pharmacology, contemporary applications and toxicology of fennel (Foeniculum vulgare Mill.). The authors note that the plant is used in traditional medicine for a wide range of digestive, endocrine, reproductive and respiratory ailments, as well as a galactagogue agent for lactating mothers. The review states that Foeniculum vulgare is among the most widely used herbs, applied for more than forty types of disorders, and contains numerous valuable compounds (volatile components, flavonoids, phenolic compounds, fatty acids, amino acids).

[2315] Ghazanfarpour M et al. Effect of fennel on vasomotor symptoms in postmenopausal women: a meta-analysis 2017;24(9):1017–1021. Menopause. 2017.

Meta-analysis examining the effect of fennel on vasomotor symptoms in postmenopausal women.

[2316] Sahraei R et al. The effect of fennel on IBS symptoms — pilot RCT 2020. J Herb Med. 2020.

Pilot randomized controlled trial of fennel for symptoms of irritable bowel syndrome (IBS).

[2317] EMA/HMPC 2013 (rev. 1). European Union herbal monograph on Pimpinella anisum L., fructus. 2013. Link

EMA/HMPC European Union herbal monograph on the fruit of Pimpinella anisum L. (anise, anisi fructus).

[2318] Picon PD et al. Randomized clinical trial of a phytotherapic compound containing Pimpinella anisum for chronic constipation2010;10:17. BMC Complement Altern Med. Link

BACKGROUND: A phytotherapic compound containing Pimpinella anisum L., Foeniculum vulgare Miller, Sambucus nigra L., and Cassia augustifolia is largely used in Brazil for the treatment of constipation. However, the laxative efficacy of the compound has never been tested in a randomized clinical trial. The aim of this study was to evaluate the efficacy and safety of the product. METHODS: This randomized, crossover, placebo-controlled, single-blinded trial included 20 patients presenting with chronic constipation according to the criteria of the American Association of Gastroenterology. The order of treatments was counterbalanced across subjects: half of the subjects received the phytotherapic compound for a 5-day period, whereas the other half received placebo for the same period. Both treatment periods were separated by a 9-day washout period followed by the reverse treatment for another 5-day period.

[2319] EFSA. Compendium on estragole — risk assessment2012. EFSA Journal. Link

EFSA compendium and risk assessment of the compound estragole.

[2320] Shojaii A, Abdollahi Fard M. Review of pharmacological properties and chemical constituents of Pimpinella anisum2012;2012:510795. ISRN Pharm. 2012. Link

Pimpinella anisum (anise), belonging to Umbelliferae family, is an aromatic plant which has been used In Iranian traditional medicine (especially its fruits) as carminative, aromatic, disinfectant, and galactagogue. Because the wide traditional usage of Pimpinella anisum for treatment of diseases, in this review published scientific reports about the composition and pharmacological properties of this plant were collected with electronic literature search of GoogleScholar, PubMed, Sciencedirect, Scopus, and SID from 1970 to 2011. So far, different studies were performed on aniseeds and various properties such as antimicrobial, antifungal, antiviral, antioxidant, muscle relaxant, analgesic and anticonvulsant activity as well as different effects on gastrointestinal system have been reported of aniseeds. It can also reduce morphine dependence and has beneficial effects on dysmenorrhea and menopausal hot flashes in women. In diabetic patients, aniseeds showed hypoglycemic and hypolipidemic effect and reduce lipid peroxidation. The most important compounds of aniseeds essential oil were trans-anetole, estragole, γ-hymachalen, para-anisaldehyde and methyl cavicol.

[2321] Tabanca N et al. Composition of Pimpinella anisum essential oil 2005. Pharm Biol. 2005.

Study on the composition of Pimpinella anisum (anise) essential oil.

[2322] Mosaffa-Jahromi M et al. Anise (Pimpinella anisum) syrup for migraine prophylaxis: open-label trial2016. Acta Med Iran. Link

Seyed Hamdollah Mosavat has made substantial contributions in conception, designing, acquisition of data and preformed clinical trial., Amin Moayedfard and Abbas Rahimi Jaberi had contribution in designing and preformed clinical trial. Zahra Sobhani and Maryam Mosaffa-Jahromi designed and prepared drugs of study. Aida Iraji has made drug biochemical assay. Seyed Hamdollah Mosavat had contribution in designing and revised the manuscript critically for important intellectual content and had contribution in designing and analyzing of data. Seyed Hamdollah Mosavat, Amin Moayedfard and Abbas Rahimi Jaberi had contribution in conception and designing and revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

[2323] Nahidi F et al. The effect of fennel and anise on uterine contractions 2009. Iran J Obstet Gynecol Infertil. 2009.

Study on the effect of fennel and anise on uterine contractions.

[2324] FDA. Consumer Update — Illicium verum and Illicium anisatum: contamination warning. 2003. . 2003. Link

FDA Consumer Update with a contamination warning regarding Illicium verum and Illicium anisatum.

[2325] Wang GW et al. Illicium verum: a review on its botany, traditional use, chemistry and pharmacology2011;136(1):10–20. J Ethnopharmacol. Link

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Illicium verum Hook. f. (Chinese star anise) has long been used in traditional Chinese medicine and food industry with the actions of dispelling cold, regulating the flow of Qi and relieving pain. MATERIALS AND METHODS: A bibliographic investigation was carried out by analyzing recognized books including Chinese herbal classic, and worldwide accepted scientific databases (Pubmed, SciFinder, Scopus and Web of Science) were searched for the available information on I. verum. RESULTS: I. verum is an aromatic evergreen tree of the family Illiciaceae. It is sometimes contaminated with highly toxic Japanese star anise (I. anisatum L.) and poisonous star anise (I. lanceolatum A. C. Smith), which contain several neurotoxic sesquiterpenes.

[2326] Ize-Ludlow D et al. Neurotoxicities in infants seen with the consumption of star anise tea2004;114(5):e653–656. Pediatrics. Link

Pediatrics case report on neurotoxicities observed in infants from the consumption of star anise tea.

[2327] Federico CA et al. Shikimic acid production by Illicium verum 2018. Bioresour Technol. 2018.

Study on shikimic acid production by Illicium verum (star anise).

[2328] Patra JK et al. Star anise (Illicium verum): chemical compounds, antiviral properties, and clinical relevance2020;9(11):1418. Plants. Link

Medicinal herbs are one of the imperative sources of drugs all over the world. Star anise (Illicium verum), an evergreen, medium-sized tree with star-shaped fruit, is an important herb with wide distribution throughout southwestern parts of the Asian continent. Besides its use as spice in culinary, star anise is one of the vital ingredients of the Chinese medicinal herbs and is widely known for its antiviral effects. It is also the source of the precursor molecule, shikimic acid, which is used in the manufacture of oseltamivir (Tamiflu®), an antiviral medication for influenza A and influenza B. Besides, several other molecules with numerous biological benefits including the antiviral effects have been reported from the same plant. Except the antiviral potential, star anise possesses a number of other potentials such as antioxidant, antimicrobial, antifungal, anthelmintic, insecticidal, secretolytic, antinociceptive, anti-inflammatory, gastroprotective, sedative properties, expectorant and spasmolytic, and estrogenic effects.

[2329] Aly SE et al. Anti-microbial activity of essential oil of star anise 2016. Pak J Biol Sci. 2016.

Study on the antimicrobial activity of star anise essential oil.

[2330] Federspil PA et al. Antimicrobial activity of Illicium verum oils 2018. Phytother Res. 2018.

Study on the antimicrobial activity of Illicium verum (star anise) oils.

[2331] Neelakantan N et al. Effect of fenugreek (Trigonella foenum-graecum L.) intake on glycemia: a meta-analysis of clinical trials2014;13:7. Nutr J. Link

BACKGROUND AND AIM: Fenugreek is a herb that is widely used in cooking and as a traditional medicine for diabetes in Asia. It has been shown to acutely lower postprandial glucose levels, but the long-term effect on glycemia remains uncertain. We systematically reviewed clinical trials of the effect of fenugreek intake on markers of glucose homeostasis. METHODS: PubMed, SCOPUS, the Cochrane Trials Registry, Web of Science, and BIOSIS were searched up to 29 Nov 2013 for trials of at least 1 week duration comparing intake of fenugreek seeds with a control intervention. Data on change in fasting blood glucose, 2 hour postload glucose, and HbA1c were pooled using random-effects models. RESULTS: A total of 10 trials were identified.

[2332] Mowla A et al. Clinical evaluation of fenugreek (Trigonella foenum-graecum) on lactation 2009. Nat Med J India. 2009.

Clinical evaluation of fenugreek (Trigonella foenum-graecum) on lactation.

[2333] Steels E et al. Physiological aspects of male libido enhanced by standardized Trigonella foenum-graecum extract and mineral formulation2011;25(9):1294–1300. Phytother Res. Link

Study on the physiological aspects of male libido enhanced by standardized Trigonella foenum-graecum extract and a mineral formulation.

[2334] Sharma RD et al. Hypoglycaemic effect of fenugreek seeds in non-insulin dependent diabetic subjects1996;16(8):1331–1339. Nutr Res. Link

Study on the hypoglycaemic effect of fenugreek seeds in non-insulin dependent diabetic subjects.

[2335] . EMA/HMPC 2011. European Union herbal monograph on Trigonella foenum-graecum L., semen. 2011. Link

EMA/HMPC European Union herbal monograph on the seed of Trigonella foenum-graecum L. (fenugreek, semen).

[2336] Sauvaire Y et al. 4-hydroxyisoleucine: a novel amino acid potentiator of insulin secretion1998;47(2):206–210. Diabetes. Link

We report the characterization of a new insulinotropic compound, 4-hydroxyisoleucine. This amino acid has been extracted and purified from fenugreek seeds, which are known in traditional medicine for their antidiabetic properties. 4-Hydroxyisoleucine increases glucose-induced insulin release, in the concentration range of 100 micromol/l to 1 mmol/l, through a direct effect on isolated islets of Langerhans from both rats and humans. The stimulating effect of 4-hydroxyisoleucine was strictly glucose dependent; indeed, ineffective at low (3 mmol/l) or basal (5 mmol/l) glucose concentrations, the amino acid potentiated the insulin secretion induced by supranormal (6.6-16.7 mmol/l) concentrations of glucose. In addition, in the isolated perfused rat pancreas, we could show 1) that the pattern of insulin secretion induced by 4-hydroxyisoleucine was biphasic, 2) that this effect occurred in the absence of any change in pancreatic alpha- and delta-cell activity, and 3) that the more glucose concentration was increased, the more insulin response was amplified. Moreover, 4-hydroxyisoleucine did not interact with other agonists of insulin secretion (leucine, arginine, tolbutamide, glyceraldehyde). Therefore, we conclude that 4-hydroxyisoleucine insulinotropic activity might, at least in part, account for fenugreek seeds' antidiabetic properties.

[2337] Khalki L et al. Fenugreek extract and lactation 2010. Fitoterapia. 2010.

Study on fenugreek extract and lactation.

[2338] EFSA. Maple syrup urine odour from fenugreek consumption — risk assessment.

EFSA risk assessment of the maple syrup urine odour arising from fenugreek consumption.

[2339] Liu Y et al. Mitigation of bioavailability differences between glucoraphanin and sulforaphane by combination with active myrosinase2015;8(8):760–768. Cancer Prev Res. Link

Glucoraphanin from broccoli and its sprouts and seeds is a water soluble and relatively inert precursor of sulforaphane, the reactive isothiocyanate that potently inhibits neoplastic cellular processes and prevents a number of disease states. Sulforaphane is difficult to deliver in an enriched and stable form for purposes of direct human consumption. We have focused upon evaluating the bioavailability of sulforaphane, either by direct administration of glucoraphanin (a glucosinolate, or β-thioglucoside-N-hydroxysulfate), or by co-administering glucoraphanin and the enzyme myrosinase to catalyze its conversion to sulforaphane at economic, reproducible and sustainable yields. We show that following administration of glucoraphanin in a commercially prepared dietary supplement to a small number of human volunteers, the volunteers had equivalent output of sulforaphane metabolites in their urine to that which they produced when given an equimolar dose of glucoraphanin in a simple boiled and lyophilized extract of broccoli sprouts. Furthermore, when either broccoli sprouts or seeds are administered directly to subjects without prior extraction and consequent inactivation of endogenous myrosinase, regardless of the delivery matrix or dose, the sulforaphane in those preparations is 3- to 4-fold more bioavailable than sulforaphane from glucoraphanin delivered without active plant myrosinase. These data expand upon earlier reports of inter- and intra-individual variability, when glucoraphanin was delivered in either teas, juices, or gelatin capsules, and they confirm that a variety of delivery matrices may be equally suitable for glucoraphanin supplementation (e.g. fruit juices, water, or various types of capsules and tablets).

[2340] Cartea ME, Velasco P. Glucosinolates in Brassica foods: bioavailability in food and significance for human health2008;7:213–229. Phytochem Rev. Link

Review on the bioavailability of glucosinolates in Brassica foods and their significance for human health.

[2341] Conaway CC et al. Disposition of glucosinolates and sulforaphane in humans after ingestion of steamed and fresh broccoli2000;38(2):168–178. Nutr Cancer. Link

The cancer-chemopreventive effects of broccoli may be attributed, in part, to isothiocyanates (ITCs), hydrolysis products of glucosinolates. Glucosinolates are hydrolyzed to their respective ITCs by the enzyme myrosinase, which is inactivated by heat. In this study, the metabolic fate of glucosinolates after ingestion of steamed and fresh broccoli was compared in 12 male subjects in a crossover design. During each 48-hour baseline period, no foods containing glucosinolates or ITCs were allowed. The subjects then consumed 200 g of fresh or steamed broccoli; all other dietary sources of ITCs were excluded. Blood and urine samples were collected during the 24-hour period after broccoli consumption.

[2342] Vig AP et al. Bio-protective effects of glucosinolates: a review 2009. LWT. 2009.

Review article on the bio-protective effects of glucosinolates.

[2343] Engel E et al. Mustard (Brassica nigra) seed oil: antibacterial activity 2011. Food Chem. 2011.

Study on the antibacterial activity of mustard (Brassica nigra) seed oil.

[2344] EFSA. Mustard — EU labeling mandatory allergen list (Regulation 1169/2011). . 2011.

Inclusion of mustard on the EU mandatory allergen labeling list (Regulation 1169/2011).

[2345] Wang H et al. Allyl isothiocyanate from mustard and gut microbiota — mechanistic review 2020. Food Funct. 2020.

Mechanistic review of allyl isothiocyanate from mustard and the gut microbiota.

[2346] Force M et al. Inhibition of enteric parasites by emulsified oil of oregano in vivo2000;14(3):213–214. Phytother Res. Link

Oil of Mediterranean oregano Oreganum vulgare was orally administered to 14 adult patients whose stools tested positive for enteric parasites, Blastocystis hominis, Entamoeba hartmanni and Endolimax nana. After 6 weeks of supplementation with 600 mg emulsified oil of oregano daily, there was complete disappearance of Entamoeba hartmanni (four cases), Endolimax nana (one case), and Blastocystis hominis in eight cases. Also, Blastocystis hominis scores declined in three additional cases. Gastrointestinal symptoms improved in seven of the 11 patients who had tested positive for Blastocystis hominis.

[2347] Burt SA. Essential oils: their antibacterial properties and potential applications in foods — a review2004;94(3):223–253. Int J Food Microbiol. Link

Review article on the antibacterial properties of essential oils and their potential applications in foods.

[2348] Sienkiewicz M et al. The antibacterial activity of oregano essential oil against clinical strains of Escherichia coli and Pseudomonas aeruginosa2012;18(7):BR203–207. Med Sci Monit. Link

INTRODUCTION: The aim of this study was to investigate the antibacterial properties of oregano (Origanum heracleoticum L.) essential oil against clinical strains of Escherichia coli and Pseudomonas aeruginosa. The antibacterial activity of oregano essential oil was investigate against 2 tested and 20 clinical bacterial strains of Escherichia coli and 20 clinical strains o Pseudomonas aeruginosa come from patients with different clinical conditions. METHODS: The agar dilution method was used for microbial growth inhibition at various concentrations ofoil. Susceptibility testing to antibiotics was carried out using disc-diffusion method. RESULTS: The results of experiments showed that the tested oil was active against all of the clinical strains from both genus of bacteria, but strains of Escherichia coli were more sensitive to tested oil. Essential oil from Origanum heracleoticum L. inhibited the growth of Escherichia coli and Pseudomonas aeruginosa clinical strains with different patters of resistance.

[2349] Bouhdid S et al. Functional and ultrastructural changes in Pseudomonas aeruginosa and Staphylococcus aureus cells induced by Origanum compactum essential oil 2010;109(4):1139–1149. J Appl Microbiol. 2010. Link

An experimental study of the functional and ultrastructural (morphological) changes induced in Pseudomonas aeruginosa and Staphylococcus aureus cells by Origanum compactum essential oil. Cellular damage was assessed by plate counts, potassium-ion leakage, flow cytometry (FC) and transmission electron microscopy (TEM). The results showed that the oil induces membrane damage: cell viability decreased, the potassium gradient dissipated, and cells accumulated bis-oxonol and propidium iodide (PI), indicating loss of membrane potential and permeability, accompanied by ultrastructural alterations.

[2350] EMA/HMPC. Origanum vulgare — herbal substance.

EMA/HMPC herbal substance document on Origanum vulgare (oregano).

[2351] Khalfa L et al. Carvacrol — mechanisms of action review 2019. Phytother Res. 2019.

Review article on the mechanisms of action of carvacrol.

[2352] Veenstra JP, Johnson JJ. Oregano (Origanum vulgare) extract for food preservation and improvement in gastrointestinal health2019. Int J Nutr. Link

The Mediterranean diet has long been known to provide a variety of health benefits such as cardiovascular protection, cancer prevention, and lowering gastrointestinal inflammation. Oregano (Origanum vulgare) is an herb prominent in the Mediterranean diet, and has been shown to possess several bioactive properties including anti-oxidant, anti-microbial, anti-inflammatory, and analgesic properties. The anti-oxidant and anti-microbial properties of oregano also make it a strong candidate as a natural food preservative. Because of the recent public concern with synthetic food preservatives, natural alternatives are increasingly being evaluated for effective food preservation. Oregano extract (OE) and essential oil (OEO) are two such agents that have shown promise as natural food preservatives. Additionally, oregano is being evaluated for its positive effect on gastrointestinal health, suggesting an additional benefit of food preservation with oregano.

[2353] . EMA/HMPC 2013. European Union herbal monograph on Thymus vulgaris L., herba. 2013. Link

EMA/HMPC European Union herbal monograph on the herb of Thymus vulgaris L. (thyme, thymi herba).

[2354] Marzian O. Treatment of acute bronchitis in children and adolescents. Non-interventional postmarketing surveillance study confirms the benefit and safety of a syrup made of extracts from thyme and ivy leaves 2007;149(suppl 1):69–74. MMW Fortschr Med. 2007.

Non-interventional postmarketing surveillance study on the treatment of acute bronchitis in children and adolescents with a syrup made of thyme and ivy leaf extracts.

[2355] Kemmerich B et al. Efficacy and tolerability of a fluid extract combination of thyme herb and ivy leaves and matched placebo in adults suffering from acute bronchitis with productive cough2006;56(9):652–660. Arzneimittelforschung. Link

STUDY OBJECTIVE: To assess the efficacy and tolerability of a fixed fluid extract combination of thyme and ivy leaves (thyme-ivy combination) and matched placebo in patients suffering from acute bronchitis with productive cough. METHODS: In a double-blind, placebo-controlled, multicentre Phase IV study 361 outpatients with acute bronchitis and > or =10 coughing fits during the day, onset of bronchial mucus production with impaired ability to cough up at a maximum of 2 days prior to recruitment, and a Bronchitis Severity Score (BSS) > or =5 score points were randomly assigned to an 11-day treatment (5.4 ml three times daily) with either thyme-ivy combination syrup (Bronchipret Saft; N=182) or placebo syrup (N=179). After the baseline examination (Visit 1 = Day 0), 2 control examinations were scheduled (Visit 2 = Day 4; Visit 3 = Day 10/end of treatment). The efficacy of study treatment on acute bronchitis was evaluated by the patient's daily counting of coughing fits during the daytime (manual counter), assessment of acute bronchitis related symptoms and by the investigator's assessment of the most important symptoms of acute bronchitis using the BSS. Evaluation of tolerability was based upon adverse event (AE) monitoring, measurement of vital signs as well as the Primary outcome was the change in frequency of coughing fits during daytime on days 7-9 according to patient's accurate daily recording with a manual counter and documentation in the diary. Treatment effects were analysed by analysis of variance (ANOVA) adjusted for centre effects.

[2356] ESCOP. Thymi herba — Thyme 2003. ESCOP Monographs. 2003.

ESCOP monograph on thyme (Thymi herba).

[2357] Burt SA. Essential oils: their antibacterial properties2004. Int J Food Microbiol. Link

Review article on the antibacterial properties of essential oils.

[2358] Sienkiewicz M et al. Antibacterial activity of thyme and lavender essential oils 2011. Med Chem. 2011.

Study on the antibacterial activity of thyme and lavender essential oils.

[2359] Salehi B et al. Thymol, thyme, and other plant sources: health and potential uses2018. Phytother Res. Link

Thymol is a naturally occurring phenol monoterpene derivative of cymene and isomer of carvacrol. Thymol (10-64\%) is one of the major constituent of essential oils of thyme (Thymus vulgaris L., Lamiaceae), a medicinal plant with several therapeutic properties. This plant, native to Mediterranean regions, is commonly used as a culinary herb and also with a long history of use for different medicinal purposes. Nowadays, thymol and thyme present a wide range of functional possibilities in pharmacy, food, and cosmetic industry. The interest in the formulation of pharmaceuticals, nutraceuticals, and cosmeceuticals based on thymol is due to several studies that have evaluated the potential therapeutic uses of this compound for the treatment of disorders affecting the respiratory, nervous, and cardiovascular systems. Moreover, this compound also exhibits antimicrobial, antioxidant, anticarcinogenesis, anti-inflammatory, and antispasmodic activities, as well as a potential as a growth enhancer and immunomodulator.

[2360] Moss M et al. Aromas of rosemary and lavender essential oils differentially affect cognition and mood in healthy adults2003;113(1):15–38. Int J Neurosci. Link

This study was designed to assess the olfactory impact of the essential oils of lavender (Lavandula angustifolia) and rosemary (Rosmarlnus officinalis) on cognitive performance and mood in healthy volunteers. One hundred and forty-four participants were randomly assigned to one of three independent groups, and subsequently performed the Cognitive Drug Research (CDR) computerized cognitive assessment battery in a cubicle containing either one of the two odors or no odor (control). Visual analogue mood questionnaires were completed prior to exposure to the odor, and subsequently after completion of the test battery. The participants were deceived as to the genuine aim of the study until the completion of testing to prevent expectancy effects from possibly influencing the data. The outcome variables from the nine tasks that constitute the CDR core battery feed into six factors that represent different aspects of cognitive functioning. Analysis of performance revealed that lavender produced a significant decrement in performance of working memory, and impaired reaction times for both memory and attention based tasks compared to controls.

[2361] Pengelly A et al. Short-term study on the effects of rosemary on cognitive function in an elderly population2012;15(1):10–17. J Med Food. Link

Rosemary (Rosmarinus officinalis L.) has traditional reputations that justify investigation for a potential role in reducing widespread cognitive decline in the elderly. A randomized, placebo-controlled, double-blinded, repeated-measures crossover study was conducted to investigate possible acute effects of dried rosemary leaf powder on cognitive performance. Twenty-eight older adults (mean age, 75 years) were tested using the Cognitive Drug Research computerized assessment system 1, 2.5, 4, and 6 hours following a placebo and four different doses of rosemary. Doses were counterbalanced, and there was a 7-day washout between visits. There was a biphasic dose-dependent effect in measures of speed of memory: the lowest dose (750 mg) of rosemary had a statistically significant beneficial effect compared with placebo (P=.01), whereas the highest dose (6,000 mg) had a significant impairing effect (P<.01). There were significant deleterious effects on other measures of cognitive performance, although these were less consistent.

[2362] Lindheimer JB et al. Short-term effects of black pepper and rosemary essential oils on cognition 2013. J Med Food. 2013.

Study on the short-term effects of black pepper and rosemary essential oils on cognition.

[2363] Habtemariam S. The therapeutic potential of rosemary (Rosmarinus officinalis) diterpenes for Alzheimer's disease2016;2016:2680409. Evid Based Complement Altern Med. 2016. Link

Rosemary (Rosmarinus officinalis L.) is one of the most economically important species of the family Lamiaceae. Native to the Mediterranean region, the plant is now widely distributed all over the world mainly due to its culinary, medicinal, and commercial uses including in the fragrance and food industries. Among the most important group of compounds isolated from the plant are the abietane-type phenolic diterpenes that account for most of the antioxidant and many pharmacological activities of the plant. Rosemary diterpenes have also been shown in recent years to inhibit neuronal cell death induced by a variety of agents both in vitro and in vivo. The therapeutic potential of these compounds for Alzheimer's disease (AD) is reviewed in this communication by giving special attention to the chemistry of the compounds along with the various pharmacological targets of the disease. The multifunctional nature of the compounds from the general antioxidant-mediated neuronal protection to other specific mechanisms including brain inflammation and amyloid beta (Aβ) formation, polymerisation, and pathologies is discussed.

[2364] Panahi Y et al. Rosemary oil vs minoxidil 2% for the treatment of androgenetic alopecia: a randomized comparative trial2015;13(1):15–21. Skinmed. Link

Randomized comparative trial of rosemary oil versus 2% minoxidil for the treatment of androgenetic alopecia.

[2365] . EMA/HMPC 2010. European Union herbal monograph on Rosmarinus officinalis L., folium. 2010. Link

EMA/HMPC European Union herbal monograph on the leaf of Rosmarinus officinalis L. (rosemary, folium).

[2366] Andrade JM et al. Rosmarinus officinalis L.: an update review of its phytochemistry and biological activity2018;4(4):FSO283. Future Sci OA. Link

The worldwide interest in the use of medicinal plants has been growing, and its beneficial effects being rediscovered for the development of new drugs. Based on their vast ethnopharmacological applications, which inspired current research in drug discovery, natural products can provide new and important leads against various pharmacological targets. This work pioneers an extensive and an updated literature review on the current state of research on Rosmarinus officinalis L., elucidating which compounds and biological activities are the most relevant. Therefore, a search was made in the databases PubMed, ScienceDirect and Web of Science with the terms 'rosemary', 'Rosmarinus officinalis', 'rosmarinic acid' 'carnosol' and 'carnosic acid', which included 286 articles published since 1990 about rosemary's pharmacological activities and their isolated compounds. According to these references, there has been an increasing interest in the therapeutic properties of this plant, regarding carnosic acid, carnosol, rosmarinic acid and the essential oil. The present manuscript provides an updated review upon the most reported activities on R. officinalis and its active constituents.

[2367] Akhondzadeh S et al. Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomized and placebo-controlled trial2003;28(1):53–59. J Clin Pharm Ther. Link

BACKGROUND: Alzheimer's disease is characterized by a slow, progressive decline in cognitive function and behaviour. Acetylcholine esterase inhibitors are the only agents approved by the Food and Drug Administration for the treatment of Alzheimer's disease. All other agents prescribed for the treatment of Alzheimer's disease are used on an off-label basis. Current research into new drugs is focused on agents that will prevent, slow down and/or halt the progress of the disease process. Salvia officinalis has been used in herbal medicine for many centuries. It has been suggested, on the basis of traditional medicine, its in vitro cholinergic binding properties and modulation of mood and cognitive performance in humans, that Salvia officinalis might potentially provide a novel natural treatment for Alzheimer's disease.

[2368] Bommer S et al. First time proof of sage's tolerability and efficacy in menopausal women with hot flushes2011;28(6):490–500. Adv Ther. Link

BACKGROUND: This trial aimed to assess the tolerability and efficacy of a fresh sage preparation in treating hot flushes and other menopausal complaints. Sage (Salvia officinalis) has been traditionally used to treat sweating and menopausal hot flushes, as well as to alleviate associated menopausal symptoms and as a general tonic. However, no clinical studies substantiating the use of sage in menopause have been published previously. METHODS: In an open, multicenter clinical trial conducted in eight practices in Switzerland, 71 patients (intent-to-treat population [ITT], n=69; with a mean age of 56.4±4.7 years, menopausal for at least 12 months, and with at least five flushes daily) were recruited and treated with a once-daily tablet of fresh sage leaves for 8 weeks after an introductory baseline week. Parameters for the evaluation of efficacy were the change in intensity and frequency of hot flushes, and total score of the mean number of intensity-rated hot flushes (TSIRHF) as determined by diary protocol over the 2-month treatment period. Other variables included assessment of the Menopause Rating Scale (MRS) by the treating physician at baseline and after 2 months of therapy.

[2369] Tildesley NTJ et al. Salvia lavandulaefolia (Spanish sage) enhances memory in healthy young volunteers2003;75(3):669–674. Pharmacol Biochem Behav. Link

Study on Salvia lavandulaefolia (Spanish sage) enhancing memory in healthy young volunteers.

[2370] . EMA/HMPC 2016. European Union herbal monograph on Salvia officinalis L., folium. 2016. Link

EMA/HMPC European Union herbal monograph on the leaf of Salvia officinalis L. (sage, folium).

[2371] Lopresti AL. Salvia (sage): a review of its potential cognitive-enhancing and protective effects2017;17(1):53–64. Drugs R D. Link

Genus Salvia, commonly known as sage, is the largest genus in the Lamiaceae family. It comprises many species traditionally used as brain-enhancing tonics. In vitro and animal studies have confirmed that several Salvia species contain a large array of active compounds that may enhance cognitive activity and protect against neurodegenerative disease. In this review, the active constituents in plants belonging to the genus Salvia are summarised, and their influence on pharmacodynamics pertinent to cognitive activity are detailed. In particular, the effects of plants belonging to the genus Salvia and their constituents on cognitive skills including memory, attention and learning are detailed. Their potential effects in dementia, including Alzheimer's disease, are also examined.

[2372] EFSA. Thujone in flavourings and other food ingredients with flavouring properties 2008. EFSA Journal. 2008.

EFSA assessment of thujone in flavourings and other food ingredients with flavouring properties.

[2373] Walch SG et al. Determination of the thujone content of Salvia officinalis 2011. Eur Food Res Technol. 2011.

Study on the determination of the thujone content of Salvia officinalis.

[2374] Vasudevan A et al. Phytochemistry and pharmacology of Origanum majorana 2012. J Pharm Pharmacol. 2012.

Review article on the phytochemistry and pharmacology of Origanum majorana (marjoram).

[2375] Bina F, Rahimi R. Sweet marjoram: a review of ethnopharmacology, phytochemistry, and biological activities2017;22(1):175–185. J Evid Based Complement Alternat Med. Link

Review of the ethnopharmacology, phytochemistry, and biological activities of sweet marjoram.

[2376] Haj-Husein I et al. The effect of marjoram (Origanum majorana) tea on the hormonal profile of women with PCOS2016;29(1):105–111. J Hum Nutr Diet. Link

BACKGROUND: In traditional medicine, marjoram herb (Origanum majorana) is locally reputed for its ability to restore hormonal balance and to regulate the menstrual cycle. Therefore, this pilot study aimed to investigate the effects of marjoram tea on the hormonal profile of women with polycystic ovary syndrome (PCOS) in a randomised, double-blind, placebo-controlled trial. METHODS: Twenty-five patients were assigned to receive marjoram tea or a placebo tea twice daily for 1 month (intervention group: n = 14; placebo group: n = 11). The hormonal and metabolic parameters measured at baseline, as well as after the intervention, were: follicle-stimulating hormone, luteinising hormone, progesterone, oestradiol, total testosterone, dehydroepiandrosterone-sulphate (DHEA-S), fasting insulin and glucose, homeostasis model assessment for insulin resistance (HOMA-IR) and glucose to insulin ratio. RESULTS: Marjoram tea significantly reduced DHEA-S and fasting insulin levels (P < 0.05) by a mean (SD) of 1.4 (0.5) μmol L(-1) and 1.9 (0.8) μU mL(-1) , respectively. In comparison to the placebo group, the change was only significant for DHEA-S (P = 0.05) but not for insulin (P = 0.08).

[2377] Prerna et al. Marjoram: a review of its biological properties 2014. Int J Pharm Sci Res. 2014.

Review article on the biological properties of marjoram.

[2378] ESCOP. Origanum majorana — monograph.

ESCOP monograph on Origanum majorana (marjoram).

[2379] Verma RS et al. Constituents of essential oil of Origanum majorana 2010. Nat Prod Res. 2010.

Study on the constituents of the essential oil of Origanum majorana (marjoram).

[2380] Hossain MA et al. Antioxidant activity and phytochemistry of marjoram 2010. J Med Plants Res. 2010.

Study on the antioxidant activity and phytochemistry of marjoram.

[2381] Cohen MM. Tulsi — Ocimum sanctum: a herb for all reasons2014;5(4):251–259. J Ayurveda Integr Med. Link

Review article on tulsi (Ocimum sanctum), presenting it as a herb for all reasons.

[2382] Bhattacharyya D et al. Controlled programmed trial of Ocimum sanctum leaf on generalized anxiety disorders 2008;10(3):176–179. Nepal Med Coll J. 2008.

Controlled programmed trial of Ocimum sanctum leaf in generalized anxiety disorders.

[2383] Saxena RC et al. Efficacy of an extract of Ocimum tenuiflorum (OciBest) in the management of general stress: a double-blind, placebo-controlled study2012;2012:894509. Evid Based Complement Alternat Med. 2012. Link

A randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy of OciBest, an extract of Ocimum tenuiflorum Linn. in symptomatic control of general stress. The participants received either placebo (n = 79) or OciBest (n = 71; 1200 mg of actives per day) for six weeks. The severity of stress-related symptoms was self-evaluated by patients at weeks 0, 2, 4 and 6 of the trial period using a symptom rating scale. After six weeks of intervention, scores of symptoms such as forgetfulness, sexual problems of recent origin, frequent feeling of exhaustion, and frequent sleep problems of recent origin decreased significantly (P ≤ 0.05) in OciBest group as compared with placebo group. Also, the total symptom scores of OciBest group revealed significant reduction (P ≤ 0.05) as compared to placebo group. The overall improvement in OciBest group was found to be 1.6 times or 39\% more in the control of general stress symptoms with respect to placebo.

[2384] Jamshidi N, Cohen MM. The clinical efficacy and safety of tulsi in humans: a systematic review of the literature2017;2017:9217567. Evid Based Complement Alternat Med. 2017. Link

Tulsi, also known as holy basil, is indigenous to the Indian continent and highly revered for its medicinal uses within the Ayurvedic and Siddha medical systems. Many in vitro, animal and human studies attest to tulsi having multiple therapeutic actions including adaptogenic, antimicrobial, anti-inflammatory, cardioprotective, and immunomodulatory effects, yet to date there are no systematic reviews of human research on tulsi's clinical efficacy and safety. We conducted a comprehensive literature review of human studies that reported on a clinical outcome after ingestion of tulsi. We searched for studies published in books, theses, conference proceedings, and electronic databases including Cochrane Library, Google Scholar, Embase, Medline, PubMed, Science Direct, and Indian Medical databases. A total of 24 studies were identified that reported therapeutic effects on metabolic disorders, cardiovascular disease, immunity, and neurocognition. All studies reported favourable clinical outcomes with no studies reporting any significant adverse events.

[2385] EFSA. Estragole — compendium on botanicals 2012. EFSA Journal. 2012.

EFSA compendium on botanicals concerning the compound estragole.

[2386] Marwat SK et al. Phytochemical constituents and pharmacological activities of sweet basil-Ocimum basilicum L 2011. Asian J Chem. 2011.

Review of the phytochemical constituents and pharmacological activities of sweet basil (Ocimum basilicum L.).

[2387] Pattanayak P et al. Ocimum sanctum Linn. A reservoir plant for therapeutic applications2010;4(7):95–105. Pharmacogn Rev. Link

Review article on Ocimum sanctum Linn. as a reservoir plant for therapeutic applications.

[2388] Eslami M et al. Effects of Satureja hortensis L. on irritable bowel syndrome: a randomized clinical trial 2014. Phytomedicine. 2014.

Randomized clinical trial on the effects of Satureja hortensis L. (summer savory) on irritable bowel syndrome (IBS).

[2389] Hadian J et al. Satureja hortensis L.: a review on its chemistry, medicinal uses and biological activities 2014. Pharmacogn Rev. 2014.

Review article on the chemistry, medicinal uses and biological activities of Satureja hortensis L. (summer savory).

[2390] Tepe B et al. In vitro antimicrobial and antioxidant activities of the essential oils and various extracts of Satureja species 2007. J Agric Food Chem. 2007.

In vitro study of the antimicrobial and antioxidant activities of essential oils and various extracts of Satureja species.

[2391] Skocibusic M et al. Phytochemical composition and antimicrobial activities of essential oils from Satureja species 2006. Phytother Res. 2006.

Study of the phytochemical composition and antimicrobial activities of essential oils from Satureja species.

[2392] ESCOP. Satureja species — herbal substance.

ESCOP monograph on Satureja species as a herbal substance.

[2393] Mihajilov-Krstev T et al. Antimicrobial activity of Satureja hortensis essential oil 2009. Cent Eur J Biol. 2009. Link

A study of the chemical composition and antimicrobial activity of summer savory (Satureja hortensis L.) essential oil. The oil was analyzed by GC and GC/MS and tested by a broth micro-well dilution method against multiresistant clinical isolates of pathogenic bacteria from 10 different genera. The main compounds were carvacrol (67%), γ-terpinene (15.3%) and p-cymene (6.73%). The oil showed significant activity against a wide spectrum of Gram-negative and Gram-positive bacteria as well as fungal strains, with inhibitory and bactericidal effects at the same concentration (MIC=MBC) for most strains.

[2394] Davarpanah S et al. Carminative effect of Satureja hortensis — animal model 2013. J Ethnopharmacol. 2013.

Animal-model study examining the carminative effect of Satureja hortensis.

[2395] Cappello G et al. Peppermint oil (Mintoil) in the treatment of irritable bowel syndrome: a prospective double blind placebo-controlled randomized trial2007;39(6):530–536. Dig Liver Dis. Link

INTRODUCTION: The use of peppermint oil in treating the irritable bowel syndrome has been studied with variable results probably due to the presence of patients affected by small intestinal bacterial overgrowth, lactose intolerance or celiac disease that may have symptoms similar to irritable bowel syndrome. AIM: The aim of the study was to test the effectiveness of enteric-coated peppermint oil in patients with irritable bowel syndrome in whom small intestinal bacterial overgrowth, lactose intolerance and celiac disease were excluded. METHODS: Fifty-seven patients with irritable bowel syndrome according to the Rome II criteria, with normal lactose and lactulose breath tests and negative antibody screening for celiac disease, were treated with peppermint oil (two enteric-coated capsules twice per day or placebo) for 4 weeks in a double blind study. The symptoms were assessed before therapy (T(0)), after the first 4 weeks of therapy (T(4)) and 4 weeks after the end of therapy (T(8)). The symptoms evaluated were: abdominal bloating, abdominal pain or discomfort, diarrhoea, constipation, feeling of incomplete evacuation, pain at defecation, passage of gas or mucus and urgency at defecation. For each symptom intensity and frequency from 0 to 4 were scored.

[2396] Khanna R et al. Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis2014;48(6):505–512. J Clin Gastroenterol. Link

GOALS: The aim of this study was to assess the efficacy and safety of enteric-coated peppermint oil capsules compared with placebo for the treatment of active irritable bowel syndrome (IBS). BACKGROUND: IBS is a common disorder that is often encountered in clinical practice. Medical interventions are limited and the focus is on symptom control. STUDY: Randomized placebo-controlled trials with a minimum treatment duration of 2 weeks were considered for inclusion. Cross-over studies that provided outcome data before the first cross-over were included. A literature search upto February 2013 identified all applicable randomized-controlled trials.

[2397] Alammar N et al. The impact of peppermint oil on the irritable bowel syndrome: a meta-analysis2019;19(1):21. BMC Complement Altern Med. Link

BACKGROUND: Peppermint oil (PO) has intrinsic properties that may benefit patients with irritable bowel syndrome (IBS) symptoms. The study objective was to determine the effect of peppermint oil in the treatment of the IBS. METHODS: We systematically searched MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (Cochrane CENTRAL), ClinicalTrials.gov, EMBASE (Ovid), and Web of Science for randomized controlled trials (RCTs) of PO for IBS. We appraised the eligible studies by the Cochrane risk of bias tool. We performed random-effects meta-analysis on primary outcomes including global improvement in IBS symptoms and abdominal pain. A PRISMA-compliant study protocol is registered in PROSPERO Register [2016, CRD42016050917].

[2398] . EMA/HMPC 2020. European Union herbal monograph on Mentha × piperita L., folium. 2020. Link

EMA/HMPC European Union herbal monograph on peppermint (Mentha × piperita L.), folium.

[2399] Madisch A et al. Treatment of functional dyspepsia with a herbal preparation 2004. Digestion. 2004.

Clinical study on the treatment of functional dyspepsia with a herbal preparation.

[2400] FDA. Menthol — pediatric warning (laryngospasm).

FDA pediatric warning regarding the laryngospasm risk associated with menthol.

[2401] Ford AC et al. Effect of antidepressants and psychological therapies in irritable bowel syndrome: an updated systematic review and meta-analysis 2019;114(1):21–39. Am J Gastroenterol. 2019. Link

An updated systematic review and meta-analysis of the effect of antidepressants and psychological therapies in irritable bowel syndrome (IBS). The authors searched MEDLINE, EMBASE, PsychINFO and the Cochrane register (up to July 2017); 53 randomized controlled trials reported in 51 articles were eligible (17 compared antidepressants with placebo, 35 compared psychological therapies with control/usual management, and one compared both). They concluded that antidepressants are efficacious in reducing IBS symptoms, and psychological therapies also appear effective, although the quality of evidence is limited and treatment effects may be overestimated.

[2402] Kasper S et al. Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of „subsyndromal" anxiety disorder2010;25(5):277–287. Int Clin Psychopharmacol. Link

This study was performed to investigate the anxiolytic efficacy of silexan, a new oral lavender oil capsule preparation, in comparison to placebo in primary care. In 27 general and psychiatric practices 221 adults suffering from anxiety disorder not otherwise specified (Diagnostic and Statistical Manual of Mental disorders-IV 300.00 or International Statistical Classification of Diseases and Related Health Problems, Tenth revision F41.9) were randomized to 80 mg/day of a defined, orally administered preparation from Lavandula species or placebo for 10 weeks with visits every 2 weeks. A Hamilton Anxiety Scale (HAMA) total score >or=18 and a total score >5 for the Pittsburgh Sleep Quality Index (PSQI) were required. The primary outcome measures were HAMA and PSQI total score decrease between baseline and week 10. Secondary efficacy measures included the Clinical Global Impressions scale, the Zung Self-rating Anxiety Scale, and the SF-36 Health Survey Questionnaire. Patients treated with silexan showed a total score decrease by 16.0+/-8.3 points (mean+/-SD, 59.3\%) for the HAMA and by 5.5+/-4.4 points (44.7\%) for the PSQI compared to 9.5+/-9.1 (35.4\%) and 3.8+/-4.1 points (30.9\%) in the placebo group (P<0.01 one-sided, intention to treat).

[2403] Kasper S et al. Lavender oil preparation Silexan is effective in generalized anxiety disorder — a randomized, double-blind comparison to placebo and paroxetine2014;17(6):859–869. Int J Neuropsychopharmacol. Link

Randomized, double-blind trial of the lavender oil preparation Silexan in generalized anxiety disorder, compared with placebo and paroxetine.

[2404] Kasper S et al. Efficacy of orally administered Silexan in patients with anxiety-related restlessness and disturbed sleep — a randomized, placebo-controlled trial 2015;25(11):1960–1967. Eur Neuropsychopharmacol. 2015. Link

A randomized, placebo-controlled trial of the efficacy of orally administered Silexan (a proprietary lavender essential-oil preparation) in patients with anxiety-related restlessness and disturbed sleep. The study evaluated the anxiolytic and sleep-improving effect of Silexan compared with placebo. Based on this search, the study reported the efficacy of Silexan in treating anxiety-related restlessness and sleep disturbance. (Detailed effect sizes were not unambiguously confirmed by the search.)

[2405] Moss M et al. Aromas of rosemary and lavender essential oils differentially affect cognition and mood in healthy adults2003. Int J Neurosci. Link

[2406] . EMA/HMPC 2012. European Union herbal monograph on Lavandula angustifolia Mill., aetheroleum. 2012.

EMA/HMPC European Union herbal monograph on lavender (Lavandula angustifolia Mill.), aetheroleum.

[2407] Henley DV et al. Prepubertal gynecomastia linked to lavender and tea tree oils2007;356(5):479–485. N Engl J Med. Link

Report linking prepubertal gynecomastia to the use of lavender and tea tree oils.

[2408] Lillehei AS et al. Effect of inhaled lavender and sleep hygiene on self-reported sleep issues2015;21(7):430–438. J Altern Complement Med. Link

OBJECTIVES: To compare the effectiveness of lavender (Lavandula angustifolia) and sleep hygiene versus sleep hygiene alone on sleep quantity and sleep quality and to determine sustained effect at two-week follow-up. DESIGN: A randomized controlled trial with investigator blinding and steps taken to blind the participants. SETTING: Participants' usual sleep setting. SUBJECTS: Seventy-nine college students with self-reported sleep issues. INTERVENTIONS: The intervention took place over five nights with baseline, postintervention, and two-week follow-up assessments. Both groups practiced good sleep hygiene and wore an inhalation patch on their chest at night.

[2409] Stein U, Greyer H, Hentschel H. Nutmeg (myristicin) poisoning — report on a fatal case and a series of cases recorded by a poison information centre2001;118(1):87–90. Forensic Sci Int. Link

In literature, cases of nutmeg abuse have been described repeatedly, but only one fatal case of poisoning was reported [1]. In the present case, myristicin (4 microg/ml) was detected for the first time in the postmortal serum of a 55-year-old woman. Identification was achieved with the aid of UV-VIS spectroscopy and TLC; for quantification, HPLC was used. Because also flunitrazepam (0.072 microg/ml) was found, death had probably been due to the combined toxic effect of both substances. From 1996 to 1998, in a series of cases, seven poisonings with nutmeg were recorded by the Erfurt Poison Information Centre. Even where higher doses (20-80 g of powder) had been ingested, a life-threatening situation was never observed.

[2410] Demetriades AK et al. Low-cost, high-risk: accidental nutmeg intoxication2005;22(3):223–225. Emerg Med J. Link

Nutmeg poisoning is rare but probably underreported and should be considered in recreational substance users with acute psychotic symptoms as well as central nervous system neuromodulatory signs that may mimic in part an anticholinergic hyperstimulation.

[2411] Carstairs SD, Cantrell FL. The spice of life: an analysis of nutmeg exposures in California2011;49(3):177–180. Clin Toxicol. Link

BACKGROUND: Nutmeg is widely used as a household spice. Numerous citations in the medical literature report its abuse as a psychoactive agent, primarily for its purported hallucinogenic effects that are thought to be due to the compound myristicin; these are primarily limited to case reports. METHODS: We performed a retrospective review of the California Poison Control System database for the years 1997-2008 for all cases of single-substance human exposure to nutmeg. RESULTS: There were a total of 119 single-substance exposures to nutmeg. Eighty-six (72.3\%) exposures were intentional. Patients intentionally abusing nutmeg were more likely to be between the ages of 13 and 20 than those with unintentional exposure to the spice (80.2\% vs. 9.1\%, p < 0.05).

[2412] EFSA. Risk assessment of allyl- and propenylbenzenes (myristicin, elemicin, safrole) in foods. EFSA Journal.

EFSA risk assessment of allyl- and propenylbenzenes (myristicin, elemicin, safrole) in foods.

[2413] . EU Regulation 1334/2008 on flavourings in food (safrole and related compounds). . 2008.

EU Regulation 1334/2008 on flavourings in food (covering safrole and related compounds).

[2414] American College of Emergency Physicians (ACEP). Nutmeg toxicity clinical review.

American College of Emergency Physicians (ACEP) clinical review of nutmeg toxicity.

[2415] Ehrenpreis JE et al. Nutmeg poisonings: a retrospective review of 10 years of reports to a poison control center2014;10(2):148–151. J Med Toxicol. Link

Nutmeg is a commonly consumed spice. The toxic effects of nutmeg have been purported to be due mainly to myristicin oil. Prior poison center series of nutmeg exposures show very few unintentional exposures of nutmeg to children younger than 13. Case series from these centers did not record drug exposures combined with nutmeg. This study is a review of Illinois Poison Center (IPC) data regarding nutmeg exposures from January of 2001 to December 2011. The goal of this study was to compare the Illinois data to the literature as well as look for current trends in nutmeg poisonings.

[2416] Milton G Sceptre 1999. *(Történeti monográfia a szerecsendió-kereskedelem és a Banda-szigetek szerepéről.)*. Nathaniel's Nutmeg: How One Man's Courage Changed the Course of History. 1999.

Historical monograph on the nutmeg trade and the role of the Banda Islands.

[2417] Akhondzadeh S et al. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial. BMC Complement Altern Med 2004;4:12. . 2004. Link

BACKGROUND: The morbidity and mortality associated with depression are considerable and continue to increase. Depression currently ranks fourth among the major causes of disability worldwide, after lower respiratory infections, prenatal conditions, and HIV/AIDS. Crocus sativus L. is used to treat depression. Many medicinal plants textbooks refer to this indication whereas there is no evidence-based document. Our objective was to compare the efficacy of stigmas of Crocus sativus (saffron) with imipramine in the treatment of mild to moderate depression in a 6-week pilot double-blind randomized trial. METHODS: Thirty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for major depression based on the structured clinical interview for DSM IV participated in the trial.

[2418] Akhondzadeh S et al. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog Neuropsychopharmacol Biol Psychiatry 2007;31(2):439–442. . 2007. Link

An 8-week pilot, double-blind, randomized clinical trial comparing the petal extract of Crocus sativus L. (saffron) with fluoxetine in the treatment of depressed outpatients. Forty adult outpatients meeting DSM-IV criteria for major depression received either 30 mg/day of petal extract or 20 mg/day of fluoxetine. The Hamilton Depression Rating Scale (HAM-D) score decreased significantly and to a similar extent in both treatment groups, suggesting that saffron petal extract had efficacy comparable to fluoxetine in this pilot trial.

[2419] Lopresti AL, Drummond PD. Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. Hum Psychopharmacol 2014;29(6):517–527. . 2014. Link

BACKGROUND: Saffron, a spice derived from the flower of Crocus sativus, has now undergone several trials examining its antidepressant effects and, in a recent meta-analysis, was confirmed to be effective for the treatment of major depression. OBJECTIVE: To provide an expanded systematic analysis of the completed clinical studies on saffron and depression, detailing dosages, extract sources, standardisations, safety profile and treatment duration; and, through a narrative review, to examine its potential antidepressant mechanisms of action. DESIGN: In the systematic review of clinical trials, electronic databases were searched for high-quality, randomised, double-blind studies, with placebo or antidepressant controls. A narrative review of in vivo and in vitro studies was conducted to examine its potential antidepressant mechanisms of action. RESULTS: In the systematic review, six studies were identified. In the placebo-comparison trials, saffron had large treatment effects and, when compared with antidepressant medications, had similar antidepressant efficacy.

[2420] Lopresti AL et al. Affron, a standardised extract from saffron (Crocus sativus L.) for the treatment of youth anxiety and depressive symptoms: a randomised, double-blind, placebo-controlled study. J Affect Disord 2018;232:349–357. . 2018. Link

BACKGROUND: Saffron has antidepressant and anxiolytic effects in adults with mild-to-moderate depression. However, this is the first study examining its mood-related effects in teenagers. METHODS: In this 8-week, randomised, double-blind, placebo-controlled study, youth aged 12-16 years, with mild-to-moderate anxiety or depressive symptoms were given tablets containing placebo or a saffron extract (affron®, 14 mg b.i.d). The youth and parent versions of the Revised Child Anxiety and Depression Scale (RCADS) were used as outcome measures. RESULTS: 80 participants were enrolled and 68 completed the study. Based on youth self-reports, affron® was associated with greater improvements in overall internalising symptoms (p = 0.049), separation anxiety (p = 0.003), social phobia (p = 0.023), and depression (p = 0.016).

[2421] Agha-Hosseini M et al. Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial. BJOG 2008;115(4):515–519. . 2008. Link

A double-blind, randomized, placebo-controlled trial of whether saffron (stigma of Crocus sativus L.) relieves premenstrual syndrome (PMS) symptoms. Women aged 20–45 with regular cycles and at least 6 months of PMS symptoms were randomized to 30 mg/day of saffron (15 mg twice daily) or placebo over two menstrual cycles. The primary outcome was the Daily Symptom Report and the secondary was the Hamilton Depression Rating Scale. The results indicate the efficacy of C. sativus in treating PMS, and its tolerable adverse-effect profile supports its use as an alternative treatment.

[2422] Akhondzadeh S et al. Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial. J Clin Pharm Ther 2010;35(5):581–588. . 2010. Link

A 16-week, randomized, double-blind, placebo-controlled, parallel-group trial of the efficacy of saffron in mild-to-moderate Alzheimer's disease. Forty-six patients with probable Alzheimer's disease were screened for the study. The trial's rationale was that Crocus sativus (saffron) may inhibit the aggregation and deposition of amyloid β in the human brain and could therefore be useful in Alzheimer's disease. The objective was to assess the efficacy of saffron in treating mild-to-moderate Alzheimer's disease.

[2423] Tóth B et al. The efficacy of saffron in the treatment of mild to moderate depression: a meta-analysis. Planta Med 2019;85(1):24–31. . 2019.

Meta-analysis of the efficacy of saffron in the treatment of mild to moderate depression.

[2424] Marx W et al. Effect of saffron supplementation on symptoms of depression and anxiety: a systematic review and meta-analysis. Nutr Rev 2019;77(8):557–571. . 2019. Link

A systematic review and meta-analysis of the effect of saffron supplementation—as both adjunctive therapy and monotherapy—on symptoms of depression and anxiety in clinical and general populations, compared with pharmacotherapy or placebo. Twenty-three studies were included. Saffron showed a large positive effect size versus placebo for depressive symptoms and was statistically significantly superior to placebo in improving depressive symptoms (in participants with or without a diagnosis of depression), with antidepressant efficacy similar to that of synthetic antidepressants.

[2425] Falsini B et al. Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration. Invest Ophthalmol Vis Sci 2010;51(12):6118–6124. . 2010. Link

A randomized, placebo-controlled, crossover study of the functional effect of short-term saffron supplementation in early age-related macular degeneration (AMD); saffron contains the antioxidant carotenoids crocin and crocetin. Twenty-five AMD patients were randomized to 20 mg/day oral saffron or placebo for 3 months, then crossed over for a further 3 months; focal electroretinograms (fERG) and clinical parameters were recorded. The 90-day, 20 mg/day saffron regimen produced statistically significant improvements versus placebo in the macular fERG parameters (amplitude and modulation threshold), indicating that saffron supplementation may induce a short-term improvement in retinal function in early AMD.

[2426] Schmidt M et al. Saffron in phytotherapy: pharmacology and clinical uses. Wien Med Wochenschr 2007;157(13–14):315–319. . 2007. Link

A review of the phytotherapeutic pharmacology and clinical uses of saffron (stigmata of Crocus sativus L.). The authors note that saffron has been used medicinally for millennia, historically against cancer and depressive mood. Promising and selective anticancer effects have been observed in vitro and in vivo (not yet in clinical trials), while antidepressant effects have been found in vivo and in clinical pilot studies. The review concludes that saffron extracts have the potential to contribute substantially to rational phytotherapy.

[2427] Anuradha K, Shyamala BN, Naidu MM. Vanilla — its science of cultivation, curing, chemistry, and nutraceutical properties2013;53(12):1250–1276. Crit Rev Food Sci Nutr. Link

Review of the science of vanilla cultivation, curing, chemistry, and nutraceutical properties.

[2428] Kumar S et al. Vanillin: a review on the recent progress of pharmacological effects 2014;8(15):37–45. Pharmacogn Rev. 2014.

Review of the recent progress on the pharmacological effects of vanillin.

[2429] Goubet N et al. Olfactory experience mediates response to pain in preterm newborns 2002;42(2):171–180. Dev Psychobiol. 2002.

Study examining how olfactory experience mediates the response to pain in preterm newborns.

[2430] Rattaz C et al. The calming effect of a familiar odor on full-term newborns 2005;26(2):86–92. J Dev Behav Pediatr. 2005. Link

An experimental study of how effectively a familiar odor soothes healthy full-term newborns during a routine heel stick. Forty-four breast-fed newborns were assigned to four groups depending on whether, before and during the heel stick, they were exposed to their mother's milk odor, a vanilla smell, an unfamiliar odor or no odor. Infants exposed to a familiar odor (mother's milk or vanilla) cried and grimaced significantly less during the recovery phase compared with the heel-stick phase, while infants smelling their mother's milk showed significantly less motor agitation during the heel stick than the other groups.

[2431] Walton NJ, Mayer MJ, Narbad A. Vanillin 2003;63(5):505–515. Phytochemistry. 2003.

Review article on vanillin.

[2432] Shyamala BN et al. Studies on the antioxidative activities of natural vanilla extract and its constituent compounds through in vitro models 2007;55(19):7738–7743. J Agric Food Chem. 2007. Link

In vitro study (β-carotene-linoleate and DPPH model systems) of the antioxidant activity of natural vanilla extract and its constituent compounds. Major components (vanillic acid, 4-hydroxybenzyl alcohol, 4-hydroxy-3-methoxybenzyl alcohol, 4-hydroxybenzaldehyde, vanillin) were identified by HPLC from the aqueous-ethanol extract. Among the constituents, 4-hydroxy-3-methoxybenzyl alcohol and 4-hydroxybenzyl alcohol showed the strongest antioxidant activity, while the whole extract was less active than the reference antioxidant BHA.

[2433] Sinha AK et al. Vanillin: pharmacological properties and analytical applications 2008;5(3):205–220. Curr Org Synth. 2008.

Review of the pharmacological properties and analytical applications of vanillin.

[2434] Lirdprapamongkol K et al. Vanillin suppresses metastatic potential of human cancer cells through PI3K inhibition 2009;57(8):3055–3063. J Agric Food Chem. 2009. Link

Experimental (cell-based and in vivo) study of the antimetastatic effect of vanillin. In human cancer cells, vanillin (and the structurally related apocynin) inhibited HGF-induced cell migration by selectively inhibiting Akt phosphorylation and phosphoinositide 3-kinase (PI3K) enzymatic activity, without affecting Met or Erk phosphorylation. In vivo (chick chorioallantoic membrane assay) vanillin also decreased angiogenesis; the aldehyde/ketone group of vanillin was found to be important for the effect.

[2435] EU Commission Regulation 1334/2008 on flavourings (defines "natural vanilla extract" vs. EU Commission Regulation 1334/2008 on flavourings (defines "natural vanilla extract" vs. "vanilla flavouring"). . 2008.

EU Commission Regulation 1334/2008 on flavourings (defining "natural vanilla extract" versus "vanilla flavouring").

[2436] . Havkin-Frenkel D, Belanger FC Wiley-Blackwell, 2011. Handbook of Vanilla Science and Technology. 2011.

Handbook of vanilla science and technology.

[2437] Sayyah M, Valizadeh J, Kamalinejad M. Anticonvulsant activity of the leaf essential oil of Laurus nobilis against pentylenetetrazole- and maximal electroshock-induced seizures2002;9(3):212–216. Phytomedicine. Link

The leaf essential oil of Laurus nobilis Linn., Lauraceae, which has been used as an antiepileptic remedy in Iranian traditional medicine, was evaluated for anticonvulsant activity against experimental seizures. The essential oil protected mice against tonic convulsions induced by maximal electroshock and especially by pentylenetetrazole. Components responsible for this effect may be methyleugenol, eugenol and pinene present in the essential oil. At anticonvulsant doses, the essential oil produced sedation and motor impairment. This effect seems to be related in part to cineol, eugenol and methyleugenol. Although the essential oil had an acceptable acute toxicity, further studies are required before any absolute conclusions can be drawn.

[2438] Khan A et al. Bay leaves improve glucose and lipid profile of people with type 2 diabetes2009;44(1):52–56. J Clin Biochem Nutr. Link

Bay leaves (Laurus nobilis) have been shown to improve insulin function in vitro but the effects on people have not been determined. The objective of this study was to determine if bay leaves may be important in the prevention and/or alleviation of type 2 diabetes. Forty people with type 2 diabetes were divided into 4 groups and given capsules containing 1, 2 or 3 g of ground bay leaves per day for 30 days or a placebo followed by a 10 day washout period. All three levels of bay leaves reduced serum glucose with significant decreases ranging from 21 to 26\% after 30 d. Total cholesterol decreased, 20 to 24\%, after 30 days with larger decreases in low density lipoprotein (LDL) cholesterol of 32 to 40\%. High density lipoprotein (HDL) cholesterol increased 29 and 20\% in the groups receiving 1 and 2 g of bay leaves, respectively.

[2439] Caputo L et al. Antimicrobial and antibiofilm activity of Laurus nobilis essential oil2017;22(6):930. Molecules. Link

Laurus nobilis is native to the southern Mediterranean region and cultivated mainly in Europe and the USA as an ornamental and medicinal plant. The chemical composition of the essential oil (EO) from leaves of L. nobilis, collected in Southern Italy, was studied by GC and GC-MS. In all, 55 compounds were identified, accounting for 91.6\% of the total oil. 1,8-Cineole (31.9\%), sabinene (12.2\%), and linalool (10.2\%) were the main components. Antimicrobial and antifungal activities of EO and 1,8-cineole were determined in vitro. The cytotoxicity of the EO was evaluated against SH-SY5Y cell line, as well as the influence of the EO on the expression of adenylate cyclase 1 (ADCY1), suggesting possible oil effects on the Central Nervous System.

[2440] Patrakar R et al. Phytochemical and pharmacological review of Laurus nobilis 2012;2(2):595–602. Int J Res Pharm Chem. 2012.

Phytochemical and pharmacological review of Laurus nobilis.

[2441] Ramos C et al. Antibacterial and antioxidant activities of Laurus nobilis L. extracts 2012;39:1–6. Ind Crops Prod. 2012.

Study of the antibacterial and antioxidant activities of Laurus nobilis L. extracts.

[2442] . EFSA Compendium of botanicals reported to contain naturally occurring substances of possible concern (Laurus nobilis section).

The Laurus nobilis section of the EFSA Compendium of botanicals reported to contain naturally occurring substances of possible concern.

[2443] . EMA/HMPC (preliminary/limited human evidence assessment). Assessment report on Laurus nobilis L., folium.

EMA/HMPC assessment report on Laurus nobilis L., folium.

[2444] Szent-Györgyi A. Hexuronic acid (vitamin C) and the paprika 1930–1932 közlemények; 1937 Nobel-díj orvostudományban. Nature. 1930.

Szent-Györgyi's report on hexuronic acid (vitamin C) and paprika.

[2445] Maoka T. Carotenoids as natural functional pigments 2020;74(1):1–16. J Nat Med. 2020.

Review of carotenoids as natural functional pigments.

[2446] Jang HH et al. (incl. Sahebkar). Effects of Capsicum annuum supplementation on the components of metabolic syndrome: a systematic review and meta-analysis2020;10:20912. Sci Rep. Link

Systematic review and meta-analysis of the effects of Capsicum annuum supplementation on the components of metabolic syndrome.

[2447] Pérez-Gálvez A, Mínguez-Mosquera MI. Carotenoid metabolism in Capsicum annuum L.: influence of cultivar and ripening stage 2002. J Agric Food Chem. 2002.

Study of carotenoid metabolism in Capsicum annuum L., including the influence of cultivar and ripening stage.

[2448] Pérez-Gálvez A et al. Carotenoid composition of paprika and oleoresin 2003;51(8):2417–2422. J Agric Food Chem. 2003.

Study of the carotenoid composition of paprika and oleoresin.

[2449] Hornero-Méndez D, Mínguez-Mosquera MI. Carotenoid pigments in dried paprika 2001;49(10):4811–4817. J Agric Food Chem. 2001.

Study of the carotenoid pigments in dried paprika.

[2450] EU Commission Implementing Regulation 1108/2010 — "Szegedi fűszerpaprika-őrlemény / Szegedi paprika" PDO bejegyzés (alapszabály: Reg. EU Commission Implementing Regulation 1108/2010 — "Szegedi fűszerpaprika-őrlemény / Szegedi paprika" PDO bejegyzés (alapszabály: Reg. 510/2006). . 2010. Link

An EU legal act registering the name "Szegedi fűszerpaprika-őrlemény / Szegedi paprika" in the register of protected designations of origin (PDO) under base Regulation (EC) No 510/2006. Per the product specification, the ground paprika is produced by grinding pepper (e.g. Capsicum annuum L. var. Longum DC.) grown from state-recognised varieties within the administrative boundaries of the Szeged paprika-growing region. The registration ties the product's protection to its geographical origin and traditional production method.

[2451] . EU Commission Implementing Regulation 622/2012 — "Kalocsai fűszerpaprika-őrlemény" PDO bejegyzés. . 2012.

EU Commission Implementing Regulation 622/2012 on the registration of "Kalocsai fűszerpaprika-őrlemény" as a protected designation of origin (PDO).

[2452] Bognár A et al. Carotenoid pigment loss in paprika during processing 2014. J Food Sci. 2014.

Study of carotenoid pigment loss in paprika during processing.

[2453] EFSA. Scientific opinion on the safety of paprika extract as a food additive 2017. EFSA Journal. 2017.

EFSA scientific opinion on the safety of paprika extract as a food additive.

[2454] Ludy MJ, Mattes RD. The effects of hedonically acceptable red pepper doses on thermogenesis and appetite 2011;102(3–4):251–258. Physiol Behav. 2011. Link

Randomized crossover human trial in 25 lean adults (spicy and non-spicy food users) testing the effect of hedonically acceptable (i.e. population-preferred, small) red pepper doses on thermogenesis and appetite within a single meal. Doses were much smaller than the ~10 g/meal commonly studied. The authors found no reliable treatment effects on appetite, energy intake or energy balance.

[2455] Mahendra P, Bisht S. Ferula assa-foetida: traditional uses and pharmacological activity 2012;6(12):141–146. Pharmacogn Rev. 2012.

Review of the traditional uses and pharmacological activity of Ferula assa-foetida.

[2456] Mala KN, Thomas J, Syam DS, Maliakel B, Krishnakumar IM. Safety and efficacy of Ferula asafoetida in functional dyspepsia: a randomized, double-blinded, placebo-controlled study2018;2018:4813601. Evid Based Complement Alternat Med. 2018. Link

Despite the availability of various synthetic drugs for the treatment of functional dyspepsia (FD), the side effects and their cost have always created a great interest in the search for novel natural alternatives for the management of gut disorders. The present contribution reports the safety and efficacy of the kitchen spice asafoetida (Ferula asafoetida) in FD for the first time. In the double-blinded, placebo-controlled study, 43 subjects diagnosed to have moderate to severe discomforts of nonulcer FD were randomized to receive hard-shell capsules (250 mg × 2/day) of either placebo (n=22) or a food-grade formulation of asafoetida (Asafin) (n=21) for 30 days. When evaluated by a set of validated indexing tools (GSRS, GDSS, and NDI), almost 81\% in the Asafin group showed significant (p < 0.01) improvement in the overall score and quality of life as compared to the placebo. At the end of the study, 66\% of subjects in the Asafin group remained symptoms-free. Although the symptoms score improved significantly in both the groups (from -5.67 to -25.29 in Asafin group versus -1.55 to -6.0 in the placebo; p ≤ 0.001), the relative percentage of subjects in the Asafin group with more than 80\% reduction in various symptoms were: bloating (58\%), appetite (69\%), postprandial fullness (74\%) motion sickness (75\%), and digestion (77\%) as compared to less than 10\% nonspecific improvement in the placebo group.

[2457] Iranshahi M. A review of volatile sulfur-containing compounds from terrestrial plants: biosynthesis, distribution and analytical methods 2012;24(4):393–434. J Essent Oil Res. 2012. Link

A review article on volatile sulfur-containing compounds (VSCs) from terrestrial plants, covering their biosynthesis, distribution and analytical methods. The author compiles 554 volatile sulfur-containing compounds reported from 43 terrestrial plant families (up to 2010) and presents their retention indices on different types of gas chromatography columns.

[2458] Bagheri SM, Rezvani ME, Vahidi AR. Anticonvulsant effect of Ferula assa-foetida oleo-gum-resin on chemical and amygdala-kindled rats 2014;6(8):408–412. N Am J Med Sci. 2014. Link

Animal (rat) study of the anticonvulsant effect of Ferula assa-foetida oleo-gum-resin (asafoetida) in chemical and amygdala-kindled seizure models. In the chemical model, asafoetida was given orally at 50 and 100 mg/kg 90 minutes before pentylenetetrazol (35 mg/kg i.p.); in the amygdala-kindling model, electrodes were implanted and effects on after-discharge duration, stage-5 seizure duration and latency were measured. The study aimed to evaluate the anticonvulsant use of asafoetida known from Iranian traditional medicine.

[2459] Amalraj A, Gopi S. Biological activities and medicinal properties of Asafoetida: A review2017;7(3):347–359. J Tradit Complement Med. Link

Ferula asafoetida Linn. is a main source of asafoetida, a strong, tenacious and sulfurous odor, and oleo-gum resin of medicinal and nutritional importance. Asafoetida has been consumed as a spice and a folk medicine for centuries. Recent studies have shown several promising activities particularly relaxant, neuroprotective, memory enhancing, digestive enzyme, antioxidant, antispasmodic, hypotensive, hepatoprotective, antimicrobial, anticarcinogenic, anticancer, anticytotoxicity, antiobesity, anthelmintic and antagonistic effect. This review effectively deals with phytochemistry and various pharmacological and clinical studies of asafoetida.

[2460] . Monash University FODMAP database — asafoetida classification (low FODMAP).

Monash University FODMAP database with the classification of asafoetida (low FODMAP).

[2461] . WHO Monographs on Selected Medicinal Plants — Ferula species safety review.

WHO Monographs on Selected Medicinal Plants safety review of Ferula species.

[2462] Iranshahy M, Iranshahi M. Traditional uses, phytochemistry and pharmacology of asafoetida (Ferula assa-foetida oleo-gum-resin) — a review2011;134(1):1–10. J Ethnopharmacol. Link

The old traditional phytomedicine asafoetida, an oleo-gum-resin obtained from the roots of different Ferula assa-foetida, is used in different countries for various purposes. Asafoetida is not only used as a culinary spice but also traditionally used to treat various diseases, including asthma, gastrointestinal disorders, intestinal parasites, etc. This oleo-gum-resin has been known to possess antifungal, anti-diabetic, anti-inflammatory, anti-mutagenic and antiviral activities. A wide range of chemical compounds including sugars, sesquiterpene coumarins and polysulfides have been isolated from this plant. Recent studies have shown new promising antiviral sesquiterpene coumarins from this old phytomedicine. The present review summarizes the information concerning the traditional uses, phytochemistry and biological activities of asafoetida.

[2463] EFSA NDA Panel. Scientific Opinion on the modification of the authorisation of a health claim related to cocoa flavanols and maintenance of normal endothelium-dependent vasodilation 2014. EFSA Journal. 2014. Link

Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the modification of the authorisation of a health claim relating cocoa flavanols to maintenance of normal endothelium-dependent vasodilation (Regulation (EC) No 1924/2006). The Panel concluded that a cause-and-effect relationship is established between consumption of cocoa flavanols from high-flavanol cocoa extract (capsules/tablets) and maintenance of normal endothelium-dependent vasodilation. To obtain the effect, 200 mg of cocoa flavanols should be consumed daily; the target population is the general population.

[2464] Sesso HD et al. Cocoa flavanols and the risk of cardiovascular events in older adults (COSMOS)2022;115(6):1490–1500. AJCN. 2022. Link

The COSMOS trial on cocoa flavanols and the risk of cardiovascular events in older adults.

[2465] Tzounis X et al. Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study2011;93(1):62–72. AJCN. Link

BACKGROUND: The absorption of cocoa flavanols in the small intestine is limited, and the majority of the flavanols reach the large intestine where they may be metabolized by resident microbiota. OBJECTIVE: We assessed the prebiotic potential of cocoa flavanols in a randomized, double-blind, crossover, controlled intervention study. DESIGN: Twenty-two healthy human volunteers were randomly assigned to either a high-cocoa flavanol (HCF) group (494 mg cocoa flavanols/d) or a low-cocoa flavanol (LCF) group (23 mg cocoa flavanols/d) for 4 wk. This was followed by a 4-wk washout period before volunteers crossed to the alternant arm. Fecal samples were recovered before and after each intervention, and bacterial numbers were measured by fluorescence in situ hybridization. A number of other biochemical and physiologic markers were measured.

[2466] Brickman AM et al. Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults2014;17(12):1798–1803. Nat Neurosci. Link

The dentate gyrus (DG) is a region in the hippocampal formation whose function declines in association with human aging and is therefore considered to be a possible source of age-related memory decline. Causal evidence is needed, however, to show that DG-associated memory decline in otherwise healthy elders can be improved by interventions that enhance DG function. We addressed this issue by first using a high-resolution variant of functional magnetic resonance imaging (fMRI) to map the precise site of age-related DG dysfunction and to develop a cognitive task whose function localized to this anatomical site. Then, in a controlled randomized trial, we applied these tools to study healthy 50-69-year-old subjects who consumed either a high or low cocoa flavanol-containing diet for 3 months. A high-flavanol intervention was found to enhance DG function, as measured by fMRI and by cognitive testing. Our findings establish that DG dysfunction is a driver of age-related cognitive decline and suggest non-pharmacological means for its amelioration.

[2467] Sloan RP et al. Cognitive and cardiovascular effects of dietary flavanols 2021;11:3837. Sci Rep. 2021.

Study of the cognitive and cardiovascular effects of dietary flavanols.

[2468] Reichardt N et al. Phenolic metabolites from gut microbiota: implications for chronic disease 2018;9(2):1135–1146. Food Funct. 2018.

Review of phenolic metabolites from gut microbiota and their implications for chronic disease.

[2469] Miller KB et al. Impact of alkalization on the antioxidant and flavanol content of commercial cocoa powders 2008;56(18):8527–8533. J Agric Food Chem. 2008. Link

Survey of the physical/chemical composition of commercial cocoa powders examining the effect of alkalization ("Dutch" processing, dutching) on flavanol and antioxidant content. Natural cocoas had the highest flavanol content, and flavanol content decreased progressively with the degree of alkalization, declining linearly as pH increased (natural cocoas averaged ~34.6 mg/g vs. ~3.9 mg/g total flavanols for heavily processed powders). Monomer, oligomer and polymer fractions all decreased with rising pH.

[2470] Heiss C et al. Vascular effects of cocoa flavanols 2019. AJCN. 2019.

Study of the vascular effects of cocoa flavanols.

[2471] Smithsonian Magazine. A Brief History of Chocolate.

Smithsonian Magazine's brief history of chocolate.

[2472] . Coe SD, Coe MD Thames & Hudson, 2013. The True History of Chocolate. 2013.

Historical monograph on the true history of chocolate.

[2473] Hu FB et al. A prospective study of egg consumption and risk of cardiovascular disease in men and women. JAMA 1999;281(15):1387–1394. . 1999. Link

CONTEXT: Reduction in egg consumption has been widely recommended to lower blood cholesterol levels and prevent coronary heart disease (CHD). Epidemiologic studies on egg consumption and risk of CHD are sparse. OBJECTIVE: To examine the association between egg consumption and risk of CHD and stroke in men and women. DESIGN AND SETTING: Two prospective cohort studies, the Health Professionals Follow-up Study (1986-1994) and the Nurses' Health Study (1980-1994). PARTICIPANTS: A total of 37851 men aged 40 to 75 years at study outset and 80082 women aged 34 to 59 years at study outset, free of cardiovascular disease, diabetes, hypercholesterolemia, or cancer. MAIN OUTCOME MEASURES: Incident nonfatal myocardial infarction, fatal CHD, and stroke corresponding to daily egg consumption as determined by a food-frequency questionnaire.

[2474] Drouin-Chartier JP et al. Egg consumption and risk of cardiovascular disease: three large prospective US cohort studies and updated meta-analysis. BMJ 2020;368:m513. . 2020. Link

Three large prospective US cohort studies and an updated meta-analysis on egg consumption and the risk of cardiovascular disease.

[2475] Zeisel SH. Choline: critical role during fetal development and dietary requirements in adults. Annu Rev Nutr 2006;26:229–250. . 2006. Link

Choline is an essential nutrient needed for the structural integrity and signaling functions of cell membranes; for normal cholinergic neurotransmission; for normal muscle function; for lipid transport from liver; and it is the major source of methyl groups in the diet. Choline is critical during fetal development, when it influences stem cell proliferation and apoptosis, thereby altering brain and spinal cord structure and function and influencing risk for neural tube defects and lifelong memory function. Choline is derived not only from the diet, but from de novo synthesis as well. Though many foods contain choline, there is at least a twofold variation in dietary intake in humans. When deprived of dietary choline, most men and postmenopausal women developed signs of organ dysfunction (fatty liver or muscle damage), while less than half of premenopausal women developed such signs. Aside from gender differences, there is significant variation in the dietary requirement for choline that can be explained by very common genetic polymorphisms.

[2476] Chung HY et al. Lutein bioavailability is higher from lutein-enriched eggs than from supplements and spinach in men. J Nutr 2004;134(8):1887–1893. . 2004. Link

Lutein may be protective against diseases such as age-related macular degeneration (ARMD). At present, data regarding bioavailability of lutein from various sources are insufficient. Healthy men (n = 10) participated in an intervention study with a crossover design. After a 2-wk washout period during which they consumed a low-carotenoid diet, the men were administered 1 of 4 lutein doses (lutein supplement, lutein ester supplement, spinach, and lutein-enriched egg) for 9 d. All lutein doses provided 6 mg lutein except for the lutein ester dose, which provided 5.5 mg lutein equivalents. Serum samples were collected from fasting subjects on d -14, 1 (baseline), 2, 3, and 10 and analyzed for changes in lutein concentration.

[2477] Evenepoel P et al. Digestibility of cooked and raw egg protein in humans as assessed by stable isotope techniques. J Nutr 1998;128(10):1716–1722. . 1998. Link

Human study (five ileostomy patients) using stable isotope techniques to assess the digestibility of cooked and raw egg protein. Subjects received a test meal containing 25 g of 13C- and 15N-labelled egg protein in cooked and then raw form; ileal effluent and breath were sampled and analysed at regular intervals. True ileal digestibility was 90.9 ± 0.8% for cooked and 51.3 ± 9.8% for raw egg protein, indicating that cooking substantially improved egg protein digestibility.

[2478] Hammond BR et al. Effects of lutein/zeaxanthin supplementation on visual performance and macular pigment. Invest Ophthalmol Vis Sci 2017. . 2017.

Study of the effects of lutein/zeaxanthin supplementation on visual performance and macular pigment.

[2479] USDA. FoodData Central — Eggs, whole, raw, fresh. NDB#01123.

USDA FoodData Central database entry for whole, raw, fresh eggs (NDB#01123).

[2480] EFSA. Scientific Opinion on Dietary Reference Values for choline. EFSA Journal 2016. . 2016.

EFSA scientific opinion on the Dietary Reference Values for choline.

[2481] Truffier JL. Action préventive et curative d'un traitement aux œufs de caille dans des cas d'allergies. Sem Hop Paris 1979;55(15–16):782–784. . 1979.

Report on the preventive and curative action of a quail egg treatment in cases of allergy.

[2482] Bruttmann G. Quail eggs in allergic rhinitis. Phytother Res 1995. . 1995.

Study on the use of quail eggs in allergic rhinitis.

[2483] Caubet JC et al. Diagnostic issues in pediatric food allergy. Curr Opin Allergy Clin Immunol 2011;11(3):251–257. . 2011.

Review article on diagnostic issues in pediatric food allergy, published in a clinical immunology journal.

[2484] USDA. FoodData Central — Eggs, quail, whole, fresh, raw. NDB#01140. Link

USDA FoodData Central database entry for the nutrient composition of whole, fresh, raw quail egg (NDB#01140).

[2485] Tunick MH et al. Composition and physicochemical properties of quail eggs. Poult Sci 2007. . 2007.

Poultry science journal article on the composition and physicochemical properties of quail eggs.

[2486] Sharaf A et al. Some biochemical studies on the nutritive value of Coturnix coturnix eggs. Egypt J Food Sci 1984. . 1984.

Biochemical study on the nutritive value of Coturnix coturnix (quail) eggs, in an Egyptian food science journal.

[2487] Stadelman WJ, Cotterill OJ. Egg Science and Technology. 4th ed. CRC Press, 1995. . 1995.

Reference textbook (4th ed.) on egg science and technology.

[2488] Sim JS. Designer eggs and their nutritional and functional significance. World Rev Nutr Diet 1998;83:89–101. . 1998.

Review chapter on designer eggs and their nutritional and functional significance.

[2489] Lewis NM et al. Omega-3 fatty acid enriched eggs and the effects on serum lipids in postmenopausal women. J Am Coll Nutr 2000;19(4):457–462. . 2000.

Study on the effects of consuming omega-3 fatty acid enriched eggs on serum lipids in postmenopausal women.

[2490] Aiken D et al. Effects of consuming omega-3 enriched eggs on blood lipids. Clin Nutr 2008. . 2008.

Clinical nutrition journal article on the effects of consuming omega-3 enriched eggs on blood lipids.

[2491] Abdelhamid AS et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2018. . 2018. Link

BACKGROUND: Researchers have suggested that omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this. OBJECTIVES: To assess effects of increased intake of fish- and plant-based omega-3 for all-cause mortality, cardiovascular (CVD) events, adiposity and lipids. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to April 2017, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to September 2016, with no language restrictions. We handsearched systematic review references and bibliographies and contacted authors. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation and/or advice to increase LCn3 or ALA intake versus usual or lower intake.

[2492] Burdge GC, Calder PC. Conversion of α-linolenic acid to longer-chain polyunsaturated fatty acids in human adults. Reprod Nutr Dev 2005;45(5):581–597. . 2005. Link

Review of the conversion of α-linolenic acid (ALA; 18:3n-3) to longer-chain n-3 polyunsaturated fatty acids (EPA, DHA) in adult humans, based mainly on stable isotope tracer studies. Increasing ALA intake raises plasma EPA proportion but not DHA; conversion to EPA is limited (especially in men) and further conversion to DHA is very low. Fractional conversion is greater in women, possibly due to a regulatory effect of estrogen; overall ALA is a limited source of longer-chain n-3 PUFA in humans.

[2493] EFSA. Scientific Opinion on Dietary Reference Values for fats. EFSA Journal 2010. . 2010.

EFSA scientific opinion on dietary reference values for fats.

[2494] Bekala-Kowalska A et al. Allergenic potential of omega-3 enriched eggs in fish-allergic patients. Clin Exp Allergy 2012. . 2012.

Allergy journal article on the allergenic potential of omega-3 enriched eggs in fish-allergic patients.

[2495] . USDA FoodData Central —(Food ID 173424); Egg, goose, whole, fresh, raw (Food ID 173425). Egg, duck, whole, fresh, raw. Link

USDA FoodData Central database entries for the composition of whole, fresh, raw duck egg and goose egg.

[2496] . Liu YC, Chen TH Food Chem 2013; 139: 1107–13. Allergenicity of duck egg proteins compared with hen egg proteins. 2013.

Food chemistry journal article comparing the allergenicity of duck egg proteins with hen egg proteins.

[2497] Hong YH et al. J Food Prot 2018; 81: 1023–8. Salmonella prevalence in duck eggs and farming environments. 2018.

Food protection journal article on Salmonella prevalence in duck eggs and farming environments.

[2498] Caboni P et al. J Food Compos Anal 2007; 20: 480–7. Lecithin and phosphatidylcholine composition of avian egg yolks (chicken, duck, goose). 2007.

Food composition analysis article on the lecithin and phosphatidylcholine composition of avian egg yolks (chicken, duck, goose).

[2499] Reglinski J et al. Clin Exp Allergy 2014. Cross-reactivity of avian egg proteins in IgE-mediated allergy. 2014.

Allergy journal article on the cross-reactivity of avian egg proteins in IgE-mediated allergy.

[2500] Wang L et al. Compr Rev Food Sci Food Saf 2018; 17: 1184–96. Pidan (century egg): chemistry, processing, and safety. 2018.

Review article on pidan (century egg): its chemistry, processing, and safety.

[2501] Kucharski R et al. Nutritional control of reproductive status in honeybees via DNA methylation. Science 2008;319(5871):1827–1830. . 2008. Link

Fertile queens and sterile workers are alternative forms of the adult female honeybee that develop from genetically identical larvae following differential feeding with royal jelly. We show that silencing the expression of DNA methyltransferase Dnmt3, a key driver of epigenetic global reprogramming, in newly hatched larvae led to a royal jelly-like effect on the larval developmental trajectory; the majority of Dnmt3 small interfering RNA-treated individuals emerged as queens with fully developed ovaries. Our results suggest that DNA methylation in Apis is used for storing epigenetic information, that the use of that information can be differentially altered by nutritional input, and that the flexibility of epigenetic modifications underpins, profound shifts in developmental fates, with massive implications for reproductive and behavioral status.

[2502] Asama T et al. Royal jelly supplementation improves menopausal symptoms. Climacteric 2018;21(6):604–609. . 2018. Link

Climacteric journal article reporting that royal jelly supplementation improves menopausal symptoms.

[2503] Pourmoradian S et al. Effects of royal jelly supplementation on glycemic control and oxidative stress factors in type 2 diabetic female. Chin J Integr Med 2014;20(5):347–352. . 2014. Link

OBJECTIVE: It has been proposed that royal jelly has antioxidant properties and may improve oxidative stress and glycemic control. Therefore, we investigated the effects of royal jelly supplementation in diabetic females. METHODS: In this pilot, parallel design randomized clinical trial, 50 female volunteers with type 2 diabetes were randomly allocated to the supplemented (25, cases) and placebo (25, cases) groups, based on random block procedure produced by Random Allocation Software, given a daily dose of 1,000 mg royal jelly soft gel or placebo, respectively, for 8 weeks. Before and after intervention, glycemic control indices, antioxidant and oxidative stress factors were measured. RESULTS: After royal jelly supplementation, the mean fasting blood glucose decreased remarkably (163.05±42.51 mg/dL vs. 149.68±42.7 mg/dL). Royal jelly supplementation resulted in significant reduction in the mean serum glycosylated hemoglobin levels (8.67\%±2.24\% vs. 7.05\%±1.45\%, P=0.001) and significant elevation in the mean insulin concentration (70.28±29.16 pmol/L vs. 86.46±27.50 pmol/L, P=0.01).

[2504] Siavash M et al. The efficacy of topical royal jelly on diabetic foot ulcers healing. Int Wound J 2014. . 2014. Link

Wound journal article on the efficacy of topical royal jelly on diabetic foot ulcer healing.

[2505] Leung R et al. Royal jelly consumption and hypersensitivity. Med J Aust 1995;162(11):604–607. . 1995. Link

BACKGROUND: Royal jelly consumption has recently been linked with acute asthma, anaphylaxis and death. A cross-sectional survey was conducted to determine the prevalence of and the relationship between royal jelly consumption and hypersensitivity reactions. METHODS: 1472 hospital employees of a teaching hospital in Hong Kong completed a questionnaire on royal jelly consumption and related allergic symptoms, and 176 questionnaire respondents and 300 consecutive asthma clinic patients were skin tested to royal jelly. RESULTS: Royal jelly consumption was high, with 461 out of 1472 subjects (31.3\%) having taken royal jelly in the past. A total of nine subjects reported 14 adverse reactions to royal jelly, including urticaria, eczema, rhinitis and acute asthma. Thirteen out of 176 questionnaire respondents (7.4\%) and 23 out of 300 consecutive asthma clinic attendees (7.3\%) had positive skin test to pure royal jelly.

[2506] Audicana M et al. Anaphylaxis induced by royal jelly. Allergy 1995;50(11):937–938. . 1995. Link

Royal jelly is the food on which are fed and which causes them to develop into queen bees. It is claimed to have rejuvenating virtues for human beings. This report describes a 15-year-old atopic woman who presented, 15 minutes after the intake of royal jelly, local angioedema, generalised urticaria, dysphonia and bronchospasm. She was given antihistaminics and corticoesteroids and responded well. The ingested product contains royal jelly, lactose and potassium sorbate. No anaphylactic reactions to lactose and sorbates have been described previously.

[2507] Bărnuţiu LI et al. Chemical composition and antimicrobial activity of royal jelly. Sci Pap Anim Sci Biotech 2011. . 2011. Link

Animal science/biotechnology article on the chemical composition and antimicrobial activity of royal jelly.

[2508] Ramadan MF, Al-Ghamdi A. Bioactive compounds and health-promoting properties of royal jelly: a review. J Funct Foods 2012;4(1):39–52. . 2012. Link

Review of the bioactive compounds and health-promoting properties of royal jelly (RJ). The authors summarize RJ's properties as a functional food, including antibacterial, anti-inflammatory, vasodilative/hypotensive, antioxidant, cholesterol-lowering and antitumor activities. The biological activities are attributed mainly to RJ's bioactive fatty acids, proteins and phenolic compounds.

[2509] Vynograd N et al. A comparative multi-centre study of the efficacy of propolis, acyclovir and placebo in the treatment of genital herpes. Phytomedicine 2000;7(1):1–6. . 2000. Link

UNLABELLED: Ninety men and women with recurrent genital HSV type 2 participated in a randomized, single-blind, masked investigator, controlled multi-centre study comparing the efficacy of ointment of Canadian propolis containing natural flavonoids with ointments of acyclovir and placebo (vehicle) on healing ability and capacity to remedy symptoms. Thirty individuals were randomized to each group. Treatment was intended to start in the blister phase. All participants had HSV type 2 isolated, confirmed by serum immunoglobulin levels. The participants were examined on the 3rd, 7th and 10th days of treatment by gynaecologists, dermatovenerologists or urologists at seven different medical centres. Apart from clinical symptoms the number and size of the herpetic lesions were noted.

[2510] Grunberger D et al. Preferential cytotoxicity on tumor cells by caffeic acid phenethyl ester. Experientia 1988;44(3):230–232. . 1988. Link

The honeybee hive product, propolis, is a folk medicine employed for treating various ailments. Many important pharmaceutical properties have been ascribed to propolis, including anti-inflammatory, antiviral, immunostimulatory and carcinostatic activities. Propolis extracts have provided an active component identified as caffeic acid phenethyl ester (CAPE), which was readily prepared in one step. Differential cytotoxicity has been observed in normal rat/human versus transformed rat/human melanoma and breast carcinoma cell lines in the presence of CAPE.

[2511] Naidu MR et al. Propolis for management of oral mucositis: a meta-analysis. Support Care Cancer 2020. . 2020.

Meta-analysis on propolis for the management of oral mucositis.

[2512] Henshaw FR et al. Topical application of propolis for diabetic foot ulcer healing: a pilot study. Wound Repair Regen 2014. . 2014. Link

AIMS: Propolis is a naturally occurring anti-inflammatory bee derived protectant resin. We have previously reported that topically applied propolis reduces inflammation and improves cutaneous ulcer healing in diabetic rodents. The aim of this study was to determine if propolis shows efficacy in a pilot study of human diabetic foot ulcer (DFU) healing and if it is well tolerated. MATERIALS: Serial consenting subjects (n=24) with DFU ≥4 weeks' duration had topical propolis applied at each clinic review for 6 weeks. Post-debridement wound fluid was analyzed for viable bacterial count and pro-inflammatory MMP-9 activity. Ulcer healing data were compared with a matched control cohort of n=84 with comparable DFU treated recently at the same center.

[2513] Bankova V. Recent trends and important developments in propolis research. Evid Based Complement Alternat Med 2005;2(1):29–32. . 2005. Link

The newest developments in propolis pharmacological research are summarized. The problem regarding biological studies, caused by the chemical variability of propolis, is discussed. The most important trends and developments in recent propolis research are outlined: biological studies performed with chemically characterized samples, bioassay-guided studies of active principles and comparative biological studies of propolis of different origin and chemical composition. These types of studies are extremely valuable with respect to propolis standardization and practical applications in therapy. They will allow scientists to connect a particular chemical propolis type to a specific type of biological activity and formulate recommendations for practitioners.

[2514] Sforcin JM. Propolis and the immune system: a review. J Ethnopharmacol 2007;113(1):1–14. . 2007. Link

Propolis has been used empirically for centuries and it was always mentioned as an immunomodulatory agent. In recent years, in vitro and in vivo assays provided new information concerning its mechanisms of action, thus a review dealing with propolis and the immune system became imperative. This review compiles data from our laboratory as well as from other researchers, focusing on its chemical composition and botanical sources, the seasonal effect on its composition and biological properties, its immunomodulatory and antitumor properties, considering its effects on antibody production and on different cells of the immune system, involving the innate and adaptive immune response. In vitro and in vivo assays demonstrated the modulatory action of propolis on murine peritoneal macrophages, increasing their microbicidal activity. Its stimulant action on the lytic activity of natural killer cells against tumor cells, and on antibody production was demonstrated. Propolis inhibitory effects on lymphoproliferation may be associated to its anti-inflammatory property.

[2515] Salatino A et al. Origin and chemical variation of Brazilian propolis. Evid Based Complement Alternat Med 2005;2(1):33–38. . 2005. Link

Propolis is a hive product containing chiefly beeswax and plant-derived substances such as resin and volatile compounds. Propolis has been used as an antiseptic and wound healer since ancient times and interest for the product has increased recently. Probably few plant species contribute as major resin sources. Green propolis derives mainly from vegetative apices of Baccharis dracunculifolia (alecrim plants). However, wide variation detected in the chemical composition suggests contributions from alternative resin plant sources. Predominant components of the resin of green propolis are cinnamic acids, chiefly compounds bearing prenyl groups.

[2516] Wagh VD. Propolis: a wonder bees product and its pharmacological potentials. Adv Pharmacol Sci 2013;2013:308249. . 2013. Link

Propolis is a natural resinous mixture produced by honey bees from substances collected from parts of plants, buds, and exudates. Due to its waxy nature and mechanical properties, bees use propolis in the construction and repair of their hives for sealing openings and cracks and smoothing out the internal walls and as a protective barrier against external invaders like snakes, lizards, and so forth, or against weathering threats like wind and rain. Bees gather propolis from different plants, in the temperate climate zone mainly from poplar. Current antimicrobial applications of propolis include formulations for cold syndrome (upper respiratory tract infections, common cold, and flu-like infections), wound healing, treatment of burns, acne, herpes simplex and genitalis, and neurodermatitis. Worldwide propolis has a tremendous popularity, but in India the studies over propolis have just started, not extensively reported except few regions of India like Maharashtra, West Bengal, Tamil Nadu, Gujrat, and Madhya Pradesh.

[2517] Winther K et al. Femal, a herbal remedy made from pollen extracts, reduces hot flushes and improves quality of life in menopausal women. Climacteric 2005;8(2):162–170. . 2005. Link

Climacteric journal article on Femal, a herbal remedy made from pollen extracts, addressing hot flushes and quality of life in menopausal women.

[2518] Steben RE, Boudreaux P. The effects of pollen and protein extracts on selected blood factors and performance of athletes. J Sports Med Phys Fitness 1978;18(3):221–226. . 1978. Link

Sports medicine journal article on the effects of pollen and protein extracts on selected blood factors and athletic performance.

[2519] Cohen SH et al. Acute allergic reaction after composite pollen ingestion. J Allergy Clin Immunol 1979. . 1979. Link

Three patients are presented who ingested a health food known as "bee pollen" and who experienced an immediate allergic reaction. Examination revealed that the bee pollen contained dandelion pollen, which belongs to the Compositae family as does ragweed. In vivo and in vitro studies demonstrated that the patients were sensitive to several Compositae family members, rather than to insect-derived antigens. In addition, radioallergosorbent inhibition studies confirmed the suspected cross-reactivity between the health food and Compositae pollens. This study indicates that atopic individuals may experience anaphylaxis from ingestion of antigens in certain food stuffs that cross-react with pollens to which they are sensitive.

[2520] Mansfield LE, Goldstein GB. Anaphylactic reaction after ingestion of local bee pollen. Ann Allergy 1996;77(1):46–48. . 1996. Link

A patient is presented who experienced an anaphylactic reaction after ingesting locally produced bee pollen to treat his spring hay fever. Evaluation revealed the patient to be extremely sensitive to mesquite pollen, a major component of the bee pollen he ingested. Passive transfer skin testing and neutralization techniques suggested that the mesquite pollen was the allergen which caused his anaphylactic reaction. Four other allergic patients were known to have systemic reactions after taking bee pollen. The patients received no warning that the bee pollen was potentially dangerous to an allergic person. It is recommended that vendors of bee pollen be required to alert allergic patients about possible risks.

[2521] Komosinska-Vassev K et al. Bee pollen: chemical composition and therapeutic application. Evid Based Complement Alternat Med 2015;2015:297425. . 2015. Link

Bee pollen is a valuable apitherapeutic product greatly appreciated by the natural medicine because of its potential medical and nutritional applications. It demonstrates a series of actions such as antifungal, antimicrobial, antiviral, anti-inflammatory, hepatoprotective, anticancer immunostimulating, and local analgesic. Its radical scavenging potential has also been reported. Beneficial properties of bee pollen and the validity for their therapeutic use in various pathological condition have been discussed in this study and with the currently known mechanisms, by which bee pollen modulates burn wound healing process.

[2522] Denisow B, Denisow-Pietrzyk M. Biological and therapeutic properties of bee pollen: a review. J Sci Food Agric 2016;96(13):4303–4309. . 2016. Link

Natural products, including bee products, are particularly appreciated by consumers and are used for therapeutic purposes as alternative drugs. However, it is not known whether treatments with bee products are safe and how to minimise the health risks of such products. Among others, bee pollen is a natural honeybee product promoted as a valuable source of nourishing substances and energy. The health-enhancing value of bee pollen is expected due to the wide range of secondary plant metabolites (tocopherol, niacin, thiamine, biotin and folic acid, polyphenols, carotenoid pigments, phytosterols), besides enzymes and co-enzymes, contained in bee pollen. The promising reports on the antioxidant, anti-inflammatory, anticariogenic antibacterial, antifungicidal, hepatoprotective, anti-atherosclerotic, immune enhancing potential require long-term and large cohort clinical studies. The main difficulty in the application of bee pollen in modern phytomedicine is related to the wide species-specific variation in its composition.

[2523] Kieliszek M et al. Pollen and bee bread as new health-oriented products: a review. Trends Food Sci Technol 2018;71:170–180. . 2018. Link

Review article on pollen and bee bread as new health-oriented products.

[2524] Campos MGR et al. Pollen composition and standardisation of analytical methods. J Apic Res 2008;47(2):154–161. . 2008. Link

Apicultural research article on pollen composition and the standardisation of analytical methods.

[2525] Fahey JW, Zhang Y, Talalay P. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. PNAS 1997;94(19):10367–10372. . 1997. Link

Induction of phase 2 detoxication enzymes [e.g., glutathione transferases, epoxide hydrolase, NAD(P)H: quinone reductase, and glucuronosyltransferases] is a powerful strategy for achieving protection against carcinogenesis, mutagenesis, and other forms of toxicity of electrophiles and reactive forms of oxygen. Since consumption of large quantities of fruit and vegetables is associated with a striking reduction in the risk of developing a variety of malignancies, it is of interest that a number of edible plants contain substantial quantities of compounds that regulate mammalian enzymes of xenobiotic metabolism. Thus, edible plants belonging to the family Cruciferae and genus Brassica (e.g., broccoli and cauliflower) contain substantial quantities of isothiocyanates (mostly in the form of their glucosinolate precursors) some of which (e.g., sulforaphane or 4-methylsulfinylbutyl isothiocyanate) are very potent inducers of phase 2 enzymes. Unexpectedly, 3-day-old sprouts of cultivars of certain crucifers including broccoli and cauliflower contain 10-100 times higher levels of glucoraphanin (the glucosinolate of sulforaphane) than do the corresponding mature plants. Glucosinolates and isothiocyanates can be efficiently extracted from plants, without hydrolysis of glucosinolates by myrosinase, by homogenization in a mixture of equal volumes of dimethyl sulfoxide, dimethylformamide, and acetonitrile at -50 degrees C. Extracts of 3-day-old broccoli sprouts (containing either glucoraphanin or sulforaphane as the principal enzyme inducer) were highly effective in reducing the incidence, multiplicity, and rate of development of mammary tumors in dimethylbenz(a)anthracene-treated rats.

[2526] Kikuchi M et al. Sulforaphane-rich broccoli sprout extract improves hepatic abnormalities in male subjects. World J Gastroenterol 2015;21(43):12457–12467. . 2015. Link

AIM: To evaluate effects of dietary supplementation of sulforaphane (SF)-rich broccoli sprout (BS) extract on hepatic abnormalities in Japanese male participants. METHODS: In a randomized, placebo-controlled, double blind trial, male participants with fatty liver received either BS capsules containing glucoraphanin [GR; a precursor of SF (n = 24)] or placebo (n = 28) for 2 mo. Liver function markers, serum levels of aspartate and alanine aminotransferases (AST and ALT, respectively) and γ-glutamyl transpeptidase (γ-GTP) and an oxidative stress marker, urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), were measured and compared in participants before and after the trial period. In an animal model, chronic liver failure was induced in Sprague-Dawley rats by successive intraperitoneal injection with N-nitrosodimethylamine (NDMA) for 4 wk. Concomitantly, rats received AIN-76 diets supplemented with or without BS extract. Thereafter, rats were sacrificed, and their sera and livers were collected to measure serum liver function markers and hepatic levels of thiobarbituric acid reactive substances (TBARS) levels and hepatic glutathione S-transferase (GST) activity, a prototypical phase 2 antioxidant enzyme.

[2527] Singh K et al. Sulforaphane treatment of autism spectrum disorder (ASD). PNAS 2014;111(43):15550–15555. . 2014. Link

Autism spectrum disorder (ASD), characterized by both impaired communication and social interaction, and by stereotypic behavior, affects about 1 in 68, predominantly males. The medico-economic burdens of ASD are enormous, and no recognized treatment targets the core features of ASD. In a placebo-controlled, double-blind, randomized trial, young men (aged 13-27) with moderate to severe ASD received the phytochemical sulforaphane (n = 29)--derived from broccoli sprout extracts--or indistinguishable placebo (n = 15). The effects on behavior of daily oral doses of sulforaphane (50-150 µmol) for 18 wk, followed by 4 wk without treatment, were quantified by three widely accepted behavioral measures completed by parents/caregivers and physicians: the Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Clinical Global Impression Improvement Scale (CGI-I). Initial scores for ABC and SRS were closely matched for participants assigned to placebo and sulforaphane. After 18 wk, participants receiving placebo experienced minimal change (<3.3\%), whereas those receiving sulforaphane showed substantial declines (improvement of behavior): 34\% for ABC (P < 0.001, comparing treatments) and 17\% for SRS scores (P = 0.017).

[2528] Yanaka A et al. Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and humans. Cancer Prev Res 2009;2(4):353–360. . 2009. Link

[2529] Riedl MA et al. Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway. Clin Immunol 2009;130(3):244–251. . 2009. Link

BACKGROUND: Cellular oxidative stress is an important factor in asthma and is thought to be the principle mechanism by which oxidant pollutants such as ozone and particulates mediate their pro-inflammatory effects. Endogenous Phase II enzymes abrogate oxidative stress through the scavenging of reactive oxygen species and metabolism of reactive chemicals. OBJECTIVE: We conducted a placebo-controlled dose escalation trial to investigate the in vivo effects of sulforaphane, a naturally occurring potent inducer of Phase II enzymes, on the expression of glutathione-s-transferase M1 (GSTM1), glutathione-s-transferase P1 (GSTP1), NADPH quinone oxidoreductase (NQO1), and hemoxygenase-1 (HO-1) in the upper airway of human subjects. METHODS: Study subjects consumed oral sulforaphane doses contained in a standardized broccoli sprout homogenate (BSH). RNA expression for selected Phase II enzymes was measured in nasal lavage cells by RT-PCR before and after sulforaphane dosing. RESULTS: All subjects tolerated oral sulforaphane dosing without significant adverse events.

[2530] Sivapalan T et al. The role of myrosinase in the transformation of glucoraphanin: bioavailability studies. J Funct Foods 2018. . 2018. Link

SCOPE: Broccoli accumulates 4-methylsulphinylbutyl glucosinolate (glucoraphanin) which is hydrolyzed to the isothiocyanate sulforaphane. Through the introgression of novel alleles of the Myb28 transcription factor from Brassica villosa, broccoli genotypes have been developed that have enhanced levels of glucoraphanin. This study seeks to quantify the exposure of human tissues to glucoraphanin and sulforaphane following consumption of broccoli with contrasting Myb28 genotypes. METHODS AND RESULTS: Ten participants are recruited into a three-phase, double-blinded, randomized crossover trial (NCT02300324), with each phase comprising consumption of 300 g of a soup made from broccoli of one of three Myb28 genotypes (Myb28B/B , Myb28B/V , Myb28V/V ). Plant myrosinases are intentionally denatured during soup manufacture. Threefold and fivefold higher levels of sulforaphane occur in the circulation following consumption of Myb28V/B and Myb28V/V broccoli soups, respectively.

[2531] Houghton CA. Sulforaphane: its "coming of age" as a clinically relevant nutraceutical in the prevention and treatment of chronic disease. Oxid Med Cell Longev 2019;2019:2716870. . 2019. Link

A growing awareness of the mechanisms by which phytochemicals can influence upstream endogenous cellular defence processes has led to intensified research into their potential relevance in the prevention and treatment of disease. Pharmaceutical medicine has historically looked to plants as sources of the starting materials for drug development; however, the focus of nutraceutical medicine is to retain the plant bioactive in as close to its native state as possible. As a consequence, the potency of a nutraceutical concentrate or an extract may be lower than required for significant gene expression. The molecular structure of bioactive phytochemicals to a large extent determines the molecule's bioavailability. Polyphenols are abundant in dietary phytochemicals, and extensive in vitro research has established many of the signalling mechanisms involved in favourably modulating human biochemical pathways. Such pathways are associated with core processes such as redox modulation and immune modulation for infection control and for downregulating the synthesis of inflammatory cytokines.

[2532] Egner PA et al. Bioavailability of sulforaphane from two broccoli sprout beverages. Cancer Prev Res 2011;4(3):384–395. . 2011. Link

One of several challenges in design of clinical chemoprevention trials is the selection of the dose, formulation, and dose schedule of the intervention agent. Therefore, a cross-over clinical trial was undertaken to compare the bioavailability and tolerability of sulforaphane from two of broccoli sprout-derived beverages: one glucoraphanin-rich (GRR) and the other sulforaphane-rich (SFR). Sulforaphane was generated from glucoraphanin contained in GRR by gut microflora or formed by treatment of GRR with myrosinase from daikon (Raphanus sativus) sprouts to provide SFR. Fifty healthy, eligible participants were requested to refrain from crucifer consumption and randomized into two treatment arms. The study design was as follows: 5-day run-in period, 7-day administration of beverages, 5-day washout period, and 7-day administration of the opposite intervention. Isotope dilution mass spectrometry was used to measure levels of glucoraphanin, sulforaphane, and sulforaphane thiol conjugates in urine samples collected daily throughout the study.

[2533] Malinow MR et al. Systemic lupus erythematosus-like syndrome in monkeys fed alfalfa sprouts: role of a nonprotein amino acid. Science 1981;216(4544):415–417. . 1981. Link

Science journal article on a systemic lupus erythematosus-like syndrome in monkeys fed alfalfa sprouts and the role of a nonprotein amino acid.

[2534] Roberts JL, Hayashi JA. Exacerbation of SLE associated with alfalfa ingestion. N Engl J Med 1983;308(22):1361. . 1983. Link

Brief medical correspondence on exacerbation of SLE associated with alfalfa ingestion.

[2535] Alcocer-Varela J et al. Effects of L-canavanine on T cells may explain the induction of systemic lupus erythematosus by alfalfa. Arthritis Rheum 1985;28(1):52–57. . 1985. Link

Alfalfa sprouts can induce systemic lupus erythematosus (SLE) in monkeys. This property of alfalfa sprouts has been attributed to their non-protein amino acid constituent, L-canavanine. Occurrence of autoimmune hemolytic anemia and exacerbation of SLE have been linked to ingestion of alfalfa tablets containing L-canavanine. In this report we show that L-canavanine has dose-related effects in vitro on human immunoregulatory cells, which could explain its lupus-inducing potential. These effects include: 1) diminution of the mitogenic response to both phytohemagglutinin and concanavalin A but not to pokeweed mitogen, as determined in both thymidine incorporation and cell cycle studies, and 2) abrogation of concanavalin A-induced suppressor cell function, which results in increased release of both IgG and DNA binding activity into supernatants by cells from normal subjects and SLE patients. These immunoregulatory effects of L-canavanine may explain the induction or exacerbation of SLE by alfalfa.

[2536] FDA Consumer Advisory. Eating raw sprouts could be risky. 1999 (renewed 2009). . 1999. Link

FDA consumer advisory warning that eating raw sprouts could be risky.

[2537] Mölgaard J et al. Alfalfa seeds lower low density lipoprotein cholesterol and apolipoprotein B concentrations. Atherosclerosis 1987;65(1–2):173–179. . 1987. Link

Fifteen patients with hyperlipoproteinemia (HLP), types IIA (n = 8), IIB (n = 3) and IV (n = 4) were given 40 g of heat prepared alfalfa seeds 3 times daily at mealtimes for 8 weeks with otherwise unchanged diet. In patients with type II HLP alfalfa treatment caused after 8 weeks a maximal lowering of pretreatment median values of total plasma cholesterol from 9.58 to 8.00 mmol/l (P less than 0.001) and low density lipoprotein (LDL) cholesterol from 7.69 to 6.33 mmol/l (P less than 0.01), which corresponds to decreases of 17\% and 18\%, respectively. Maximal decrease was 26\% in total cholesterol and 30\% in LDL cholesterol. In two patients with hypercholesterolemia the LDL cholesterol decreased less than 5\%. Apolipoprotein B decreased in the same period from 2.17 to 1.43 g/l (P less than 0.05) in type II HLP, corresponding to 34\% decrease, whereas apolipoprotein A-I did not change. Body weight increased slightly during the first 4 weeks of alfalfa treatment (P less than 0.001) probably because of the caloric content in the alfalfa seeds.

[2538] Bari L et al. Pathogen contamination in alfalfa sprouts: a critical review. Compr Rev Food Sci Food Saf 2009;8(4):343–356. . 2009.

Critical review article on pathogen contamination in alfalfa sprouts.

[2539] Taormina PJ et al. Infections associated with eating seed sprouts: an international concern. Emerg Infect Dis 1999;5(5):626–634. . 1999. Link

Infectious disease article on infections associated with eating seed sprouts as an international concern.

[2540] Knudsen KE. Carbohydrate and lignin contents of plant materials. Br J Nutr 1997. . 1997. Link

Nutrition journal article on the carbohydrate and lignin contents of plant materials.

[2541] Mubarak AE. Nutritional composition and antinutritional factors of mung bean seeds (Phaseolus aureus) as affected by some home traditional processes2005;89(4):489–495. Food Chem. Link

Study of the effect of home traditional processes (soaking, dehulling, boiling, autoclaving, microwave cooking, germination) on the nutritional composition and antinutritional factors of mung bean (Phaseolus aureus) seeds. Germination and cooking processes significantly decreased fat, carbohydrate fractions, antinutritional factors and total ash, while all processes improved in vitro protein digestibility and protein efficiency ratio (PER).

[2542] Kim DK et al. Functional properties of mung bean sprout (Vigna radiata). Korean J Food Sci Technol 2017. . 2017.

Food science journal article on the functional properties of mung bean sprout (Vigna radiata).

[2543] Wani SA et al. Mung bean (Vigna radiata): a comprehensive review of its nutritional value, phytochemistry and health benefits. J Food Sci 2017. . 2017. Link

Comprehensive review article on the nutritional value, phytochemistry and health benefits of mung bean (Vigna radiata).

[2544] Yao Y et al. Mung bean protein hydrolysate inhibits angiotensin I-converting enzyme. Food Chem 2018. . 2018. Link

Mung bean Protein hydrolyses (MBPHs) have attracted a great deal of attention due to their variety of biological activities. In present study, MBPHs were fractionate according to the molecular mass into three fractions of MBPHs-I (<3 kDa), MBPHs-II (3-10 kDa) and MBPHs-III (>10 kDa). Their antioxidant activity and angiotensin-I converting enzyme (ACE) inhibitory of were investigated in vitro. Results showed that the alcalase-derived hydrolysate exhibited the highest degree of hydrolysis (DH) and trichloroacetic acid-nitrogen soluble index (TCA-NSI) versus those of other enzyme hydrolysates. MBPHs-I presented the best scavenge DPPH, hydroxyl radicals, superoxide radicals, Fe2+ chelating activities, and the best ACE inhibitory activity (IC50 = 4.66 μg/mL) than that of MBPHs and MBPHs-III. And MBPHs-I rich in hydrophobic and aromatic amino acids, and its secondary structure mainly contain α-helix, β-sheet and irregular coiled.

[2545] Tang D et al. A review of phytochemistry, metabolite changes, and medicinal uses of the common food mung bean. Chem Cent J 2014;8(1):4. . 2014. Link

The seeds and sprouts of mung bean (Vigna radiata), a common food, contain abundant nutrients with biological activities. This review provides insight into the nutritional value of mung beans and its sprouts, discussing chemical constituents that have been isolated in the past few decades, such as flavonoids, phenolic acids, organic acids, amino acids, carbohydrates, and lipids. Moreover, we also summarize dynamic changes in metabolites during the sprouting process and related biological activities, including antioxidant, antimicrobial, anti-inflammatory, antidiabetic, antihypertensive, lipid metabolism accommodation, antihypertensive, and antitumor effects, etc., with the goal of providing scientific evidence for better application of this commonly used food as a medicine.

[2546] Mubarak AE. Nutritional composition and antinutritional factors of mung bean seeds (Phaseolus aureus) as affected by some home traditional processes. Food Chem 2005;89(4):489–495. . 2005. Link

[2548] Frank C et al. Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med 2011;365:1771–1780. . 2011. Link

Medical journal article on the epidemic profile of the Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany.

[2549] Ben-Arye E et al. Wheat grass juice in the treatment of active distal ulcerative colitis. Scand J Gastroenterol 2002;37(4):444–449. . 2002. Link

Gastroenterology journal article on wheat grass juice in the treatment of active distal ulcerative colitis.

[2550] Marawaha RK et al. Wheat grass juice reduces transfusion requirement in patients with thalassemia major. Indian Pediatr 2004;41(7):716–720. . 2004. Link

Wheat grass juice is the juice extracted from the pulp of wheat grass and has been used as a general-purpose health tonic for several years. Several of our patients in the thalassemia unit began consuming wheat grass juice after anecdotal accounts of beneficial effects on transfusion requirements. These encouraging experiences prompted us to evaluate the effect of wheat grass juice on transfusion requirements in patients with transfusion dependent beta thalassemia. Families of patients raised the wheat grass at home in kitchen garden/pots. The patients consumed about 100 mL of wheat grass juice daily. Each patient acted as his own control.

[2551] Bar-Sela G et al. Wheat grass juice may improve hematological toxicity related to chemotherapy in breast cancer. Nutr Cancer 2007;58(1):43–48. . 2007. Link

Myelotoxicity induced by chemotherapy may become life-threatening. Neutropenia may be prevented by granulocyte colony-stimulating factors (GCSF), and epoetin may prevent anemia, but both cause substantial side effects and increased costs. According to non-established data, wheat grass juice (WGJ) may prevent myelotoxicity when applied with chemotherapy. In this prospective matched control study, 60 patients with breast carcinoma on chemotherapy were enrolled and assigned to an intervention or control arm. Those in the intervention arm (A) were given 60 cc of WGJ orally daily during the first three cycles of chemotherapy, while those in the control arm (B) received only regular supportive therapy. Premature termination of treatment, dose reduction, and starting GCSF or epoetin were considered as "censoring events." Response rate to chemotherapy was calculated in patients with evaluable disease.

[2552] Schnabel CF. Wheat grass: nature's finest medicine. (Historical reference, 1930s).

Historical reference (1930s) on wheat grass as a medicinal substance.

[2553] Wigmore A. The Wheatgrass Book. Avery Publishing, 1985 (historical/non-peer-reviewed reference). . 1985.

Popular book (historical, non-peer-reviewed reference) on wheatgrass.

[2554] Mujoriya R et al. A study on wheat grass and its nutritional value. Food Sci Qual Manag 2011. . 2011. Link

Food science journal article on wheat grass and its nutritional value.

[2555] Singh K et al. Wheat grass: an alternative household nutritional food security. Int Res J Pharm 2012. . 2012.

Pharmacy journal article on wheat grass as an alternative household nutritional food security source.

[2556] Bircher RR. The Bircher-Benner story. Nutr Today 1973 (historical reference). . 1973.

Historical reference (nutrition journal) on the Bircher-Benner story.

[2557] Ghavidel RA, Prakash J. The impact of germination and dehulling on nutrients, antinutrients, in vitro iron and calcium bioavailability and in vitro starch and protein digestibility of some legume seeds. LWT Food Sci Technol 2007;40(7):1292–1299. . 2007. Link

Food science journal article on the impact of germination and dehulling on nutrients, antinutrients, and in vitro iron, calcium, starch and protein digestibility of some legume seeds.

[2558] Kataria A et al. Effect of germination on the protein and sugar content of moth bean. Plant Foods Hum Nutr 1989;39(2):157–162. . 1989.

Journal article on the effect of germination on the protein and sugar content of moth bean.

[2559] Hurrell RF et al. Soy protein, phytate, and iron absorption in humans. Am J Clin Nutr 1992;56(3):573–578. . 1992. Link

The effect of reducing the phytate in soy-protein isolates on nonheme-iron absorption was examined in 32 human subjects. Iron absorption was measured by using an extrinsic radioiron label in liquid-formula meals containing hydrolyzed corn starch, corn oil, and either egg white or one of a series of soy-protein isolates with different phytate contents. Iron absorption increased four- to fivefold when phytic acid was reduced from its native amount of 4.9-8.4 to less than 0.01 mg/g of isolate. Even relatively small quantities of residual phytate were strongly inhibitory and phytic acid had to be reduced to less than 0.3 mg/g of isolate (corresponding to less than 10 mg phytic acid/meal) before a meaningful increase in iron absorption was observed. However, even after removal of virtually all the phytic acid, iron absorption from the soy-protein meal was still only half that of the egg white control. It is concluded that phytic acid is a major inhibitory factor of iron absorption in soy-protein isolates but that other factors contribute to the poor bioavailability of iron from these products.

[2560] Bazzano LA et al. Non-soy legume consumption lowers cholesterol levels: a meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis 2011;21(2):94–103. . 2011. Link

BACKGROUND AND AIMS: Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids. METHODS AND RESULTS: Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol.

[2561] Carlson JL et al. Health effects and sources of prebiotic dietary fiber. Curr Dev Nutr 2018;2(3):nzy005. . 2018. Link

Prebiotic dietary fibers act as carbon sources for primary and secondary fermentation pathways in the colon, and support digestive health in many ways. Fructooligosaccharides, inulin, and galactooligosaccharides are universally agreed-upon prebiotics. The objective of this paper is to summarize the 8 most prominent health benefits of prebiotic dietary fibers that are due to their fermentability by colonic microbiota, as well as summarize the 8 categories of prebiotic dietary fibers that support these health benefits. Although not all categories exhibit similar effects in human studies, all of these categories promote digestive health due to their fermentability. Scientific and regulatory definitions of prebiotics differ greatly, although health benefits of these compounds are uniformly agreed upon to be due to their fermentability by gut microbiota. Scientific evidence suggests that 8 categories of compounds all exhibit health benefits related to their metabolism by colonic taxa.

[2562] Wong THT et al. The effect of lentil consumption on glycemic response. J Funct Foods 2017. . 2017.

Functional foods journal article on the effect of lentil consumption on glycemic response.

[2563] Kuo YH et al. Effects of germination on bioactive compounds and antioxidant capacity of red lentil sprouts 2014;162:1014–1020. (Lencse-specifikus csíráztatási antinutriens + polifenol-változás.)**. Food Chem. 2014.

Food chemistry journal article on the effects of germination on bioactive compounds and antioxidant capacity of red lentil sprouts (lentil-specific antinutrient and polyphenol changes).

[2564] Vidal-Valverde C, Frias J. Changes in carbohydrates during germination of faba bean and lupin seeds. Z Lebensm Unters Forsch A 1992. . 1992. Link

Food research journal article on changes in carbohydrates during germination of faba bean and lupin seeds.

[2565] Rennard BO et al. Chicken soup inhibits neutrophil chemotaxis in vitro. Chest 2000;118(4):1150–1157. . 2000. Link

Chicken soup has long been regarded as a remedy for symptomatic upper respiratory tract infections. As it is likely that the clinical similarity of the diverse infectious processes that can result in "colds" is due to a shared inflammatory response, an effect of chicken soup in mitigating inflammation could account for its attested benefits. To evaluate this, a traditional chicken soup was tested for its ability to inhibit neutrophil migration using the standard Boyden blindwell chemotaxis chamber assay with zymosan-activated serum and fMet-Leu-Phe as chemoattractants. Chicken soup significantly inhibited neutrophil migration and did so in a concentration-dependent manner. The activity was present in a nonparticulate component of the chicken soup. All of the vegetables present in the soup and the chicken individually had inhibitory activity, although only the chicken lacked cytotoxic activity.

[2566] Shaw G et al. Vitamin C-enriched gelatin supplementation before intermittent activity augments collagen synthesis. Am J Clin Nutr 2017;105(1):136–143. . 2017. Link

BACKGROUND: Musculoskeletal injuries are the most common complaint in active populations. More than 50\% of all injuries in sports can be classified as sprains, strains, ruptures, or breaks of musculoskeletal tissues. Nutritional and/or exercise interventions that increase collagen synthesis and strengthen these tissues could have an important effect on injury rates. OBJECTIVE: This study was designed to determine whether gelatin supplementation could increase collagen synthesis. DESIGN: Eight healthy male subjects completed a randomized, double-blinded, crossover-design study in which they consumed either 5 or 15 g of vitamin C-enriched gelatin or a placebo control. After the initial drink, blood was taken every 30 min to determine amino acid content in the blood.

[2567] Yamadera W et al. Glycine ingestion improves subjective sleep quality. Sleep Biol Rhythms 2007;5(2):126–131. . 2007. Link

Human study of the effect of glycine ingestion (3 g) before bedtime on subjective sleep quality in volunteers with unsatisfactory sleep, with polysomnographic (PSG) analysis. Glycine improved subjective sleep quality and sleep efficacy and shortened latency to sleep onset and to slow-wave sleep without altering sleep architecture; it also reduced daytime sleepiness and improved performance on memory recognition tasks.

[2568] Wischmeyer PE. Glutamine: role in critical illness and ongoing clinical trials. JPEN J Parenter Enteral Nutr 2008. . 2008. Link

PURPOSE OF REVIEW: This review will assess recent clinical and mechanistic data examining glutamine's ability to reduce morbidity and mortality in critical illness. RECENT FINDINGS: Updated metaanalysis data reveal a significant benefit of glutamine supplementation on mortality, length of stay, and infectious morbidity in critical illness. Recent data support glutamine's use in critically ill patients requiring parenteral nutrition and new data reveal safety and efficacy in head-injured patients. Further, new findings on glutamine's beneficial effect on insulin resistance in critical illness will be reviewed. Recent laboratory data have clarified a number of key mechanistic pathways by which glutamine may improve outcome in critical illness. SUMMARY: Severe glutamine deficiencies occur rapidly in critical illness.

[2569] Monro JA et al. The risk of lead contamination in bone broth diets. Med Hypotheses 2013;80(4):389–390. . 2013. Link

The preparation and consumption of bone broth is being increasingly recommended to patients, for example as part of the gut and psychology syndrome (GAPS) diet for autism, attention-deficit hyperactivity disorder, dyslexia, dyspraxia, depression and schizophrenia, and as part of the paleolithic diet. However, bones are known to sequester the heavy metal lead, contamination with which is widespread throughout the modern environment. Such sequestered lead can then be mobilised from the bones. We therefore hypothesised that bone broth might carry a risk of being contaminated with lead. A small, blinded, controlled study of lead concentrations in three different types of organic chicken broth showed that such broths do indeed contain several times the lead concentration of the water with which the broth is made. In particular, broth made from skin and cartilage taken off the bone once the chicken had been cooked with the bones in situ, and chicken-bone broth, were both found to have markedly high lead concentrations, of 9.5 and 7.01 μg L(-1), respectively (compared with a control value for tap water treated in the same way of 0.89 μg L(-1)).

[2570] Hsu DJ et al. Essential and toxic metals in animal bone broths. Food Nutr Res 2017;61(1):1347478. . 2017. Link

Background: This investigation examines the extraction of metals from animal bones into broth, and assesses whether bone broths are good sources of essential metals and the risks associated with the consumption of toxic metals. Method:Three sets of controlled experiments were performed to study the factors (cooking time, acidity, bone type and animal species) that influence metal extractions. Three types of animal bone broth-based foods were also tested. Results: Reducing the broth pH from 8.38 to 5.32 significantly (p < 0.05) increased Ca and Mg extraction by factors of 17.4 and 15.3, respectively. A long cooking time, > 8 h, yielded significantly higher (p < 0.05) Ca and Mg extraction than shorter cooking times. The extraction characteristics of metals, particularly Ca, Mg, Cu and Al, from the leg and rib bones differed.

[2571] Mar-Solís LM et al. Metabolomic profiling of bone broth consumption — pilot study. 2024. . 2024.

Pilot metabolomic profiling study on bone broth consumption.

[2572] Wu G. Functional amino acids in nutrition and health. Amino Acids 2017. . 2017. Link

The recent years have witnessed growing interest in biochemistry, physiology and nutrition of amino acids (AA) in growth, health and disease of humans and other animals. This results from the discoveries of AA in cell signaling involving protein kinases, G protein-coupled receptors, and gaseous molecules (i.e., NO, CO and H2S). In addition, nutritional studies have shown that dietary supplementation with several AA (e.g., arginine, glutamine, glutamate, leucine, and proline) modulates gene expression, enhances growth of the small intestine and skeletal muscle, or reduces excessive body fat. These seminal findings led to the new concept of functional AA, which are defined as those AA that participate in and regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of the organisms. Functional AA hold great promise in prevention and treatment of metabolic diseases (e.g., obesity, diabetes, and cardiovascular disorders), intrauterine growth restriction, infertility, intestinal and neurological dysfunction, and infectious disease (including viral infections).

[2573] Tang C et al. Collagen peptides and intestinal barrier — preclinical evidence. 2024. . 2024.

Study presenting preclinical evidence on collagen peptides and the intestinal barrier.

[2574] Iwai K et al. Identification of food-derived collagen peptides in human blood after oral ingestion. J Agric Food Chem 2005;53(16):6531–6536. . 2005. Link

In the present study, we identified several food-derived collagen peptides in human blood after oral ingestion of some gelatin hydrolysates. Healthy human volunteers ingested the gelatin hydrolysates (9.4-23 g) from porcine skin, chicken feet, and cartilage after 12 h of fasting. Negligible amounts of the peptide form of hydroxyproline (Hyp) were observed in human blood before the ingestion. After the oral ingestion, the peptide form of Hyp significantly increased and reached a maximum level (20-60 nmol/mL of plasma) after 1-2 h and then decreased to half of the maximum level at 4 h after the ingestion. Major constituents of food-derived collagen peptides in human serum and plasma were identified as Pro-Hyp. In addition, small but significant amounts of Ala-Hyp, Ala-Hyp-Gly, Pro-Hyp-Gly, Leu-Hyp, Ile-Hyp, and Phe-Hyp were contained.

[2575] Rosner F. Moses Maimonides on chicken soup. JAMA 1980. . 1980.

Medical history journal article on Moses Maimonides on chicken soup.

[2576] Escoffier A. Le Guide Culinaire. 1903. . 1903.

Classic culinary reference work (Le Guide Culinaire, 1903).

[2577] Proksch E et al. Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study. Skin Pharmacol Physiol 2014;27(1):47–55. . 2014. Link

Various dietary supplements are claimed to have cutaneous anti-aging properties; however, there are a limited number of research studies supporting these claims. The objective of this research was to study the effectiveness of collagen hydrolysate (CH) composed of specific collagen peptides on skin biophysical parameters related to cutaneous aging. In this double-blind, placebo-controlled trial, 69 women aged 35-55 years were randomized to receive 2.5 g or 5.0 g of CH or placebo once daily for 8 weeks, with 23 subjects being allocated to each treatment group. Skin elasticity, skin moisture, transepidermal water loss and skin roughness were objectively measured before the first oral product application (t0) and after 4 (t1) and 8 weeks (t2) of regular intake. Skin elasticity (primary interest) was also assessed at follow-up 4 weeks after the last intake of CH (t3, 4-week regression phase). At the end of the study, skin elasticity in both CH dosage groups showed a statistically significant improvement in comparison to placebo.

[2578] Czajka A et al. Daily oral supplementation with collagen peptides improves skin parameters. Nutr Res 2018;57:97–108. . 2018. Link

Aging is a multifactorial and natural process that causes physiological changes in organs, tissues and cells over time. In the skin and cartilage, aging leads to a decrease in the synthesis and changes in the arrangement of proteoglycans and collagen, in addition to the loss of glycosaminoglycans, which are responsible for the integrity and health of these tissues. We hypothesized that daily oral supplementation with a liquid nutraceutical containing hydrolyzed fish collagen, vitamins, antioxidants and other active ingredients could improve skin texture and elasticity, and in addition have a protective effect on joint health. A double-blind, randomized, placebo-controlled clinical trial was conducted on 120 subjects who consumed either the test product or placebo on a daily basis for 90 days. Subjects consuming the test product had an overall significant increase in skin elasticity (+40\%; P < .0001) when compared to placebo. Histological analysis of skin biopsies revealed positive changes in the skin architecture, with a reduction in solar elastosis and improvement in collagen fiber organization in the test product group.

[2579] Choi FD et al. Oral collagen supplementation: a systematic review of dermatological applications2019;18(1):9–16. J Drugs Dermatol. Link

Systematic review of the dermatological applications of oral collagen supplementation.

[2580] Bello AE & Oesser S. Collagen hydrolysate for the treatment of osteoarthritis. Curr Med Res Opin 2006;22(11):2221–2232. . 2006. Link

BACKGROUND: There is a need for an effective treatment for the millions of people in the United States with osteoarthritis (OA), a degenerative joint disease. The demand for treatments, both traditional and non-traditional, will continue to grow as the population ages. SCOPE: This article reviews the medical literature on the preclinical and clinical research on a unique compound, collagen hydrolysate. Articles were obtained through searches of the PubMed database (www.pubmed.gov) through May 2006 using several pairs of key words (collagen hydrolysate and osteoarthritis; collagen hydrolysate and cartilage; collagen hydrolysate and chondrocytes; collagen hydrolysate and clinical trial) without date limits. In addition, other sources of information, such as abstracts presented at scientific congresses and articles in the German medical literature not available on PubMed, were reviewed and included based on the authors' judgment of their relevance to the topic of the review. FINDINGS: According to published research, orally administered collagen hydrolysate has been shown to be absorbed intestinally and to accumulate in cartilage.

[2581] Clark KL et al. 24-week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Curr Med Res Opin 2008;24(5):1485–1496. . 2008. Link

BACKGROUND: Collagen hydrolysate is a nutritional supplement that has been shown to exert an anabolic effect on cartilage tissue. Its administration appears beneficial in patients with osteoarthritis. OBJECTIVE: To investigate the effect of collagen hydrolysate on activity-related joint pain in athletes who are physically active and have no evidence of joint disease. DESIGN AND SETTING: A prospective, randomized, placebo-controlled, double-blind study was conducted at Penn State University in University Park, Pennsylvania. Parameters including joint pain, mobility, and inflammation were evaluated with the use of a visual analogue scale during a 24-week study phase. STUDY PARTICIPANTS: Between September 2005 and June 2006, 147 subjects who competed on a varsity team or a club sport were recruited.

[2582] Kviatkovsky SA et al. Collagen peptide supplementation for pain and function. Curr Sports Med Rep 2019. . 2019.

Sports medicine journal article on collagen peptide supplementation for pain and function.

[2583] Konig D et al. Specific collagen peptides improve bone mineral density and bone markers in postmenopausal women — 1-year RCT. Nutrients 2018;10(1):97. . 2018. Link

Introduction: Investigations in rodents as well as in vitro experiments have suggested an anabolic influence of specific collagen peptides (SCP) on bone formation and bone mineral density (BMD). The goal of the study was to investigate the effect of 12-month daily oral administration of 5 g SCP vs. placebo (CG: control group) on BMD in postmenopausal women with primary, age-related reduction in BMD. Methods: 131 women were enrolled in this randomized, placebo-controlled double-blinded investigation. The primary endpoint was the change in BMD of the femoral neck and the spine after 12 months. In addition, plasma levels of bone markers-amino-terminal propeptide of type I collagen (P1NP) and C-telopeptide of type I collagen (CTX 1)-were analysed. Results: A total of 102 women completed the study, but all subjects were included in the intention-to-treat (ITT) analysis (age 64.3 ± 7.2 years; Body Mass Index, BMI 23.6 ± 3.6 kg/m²; T-score spine -2.4 ± 0.6; T-score femoral neck -1.4 ± 0.5).

[2586] Shigemura Y et al. Dose-dependent changes in hydroxyproline-containing peptide levels in human plasma. Br J Nutr 2014. . 2014. Link

Journal article (Br J Nutr, 2014) examining dose-dependent changes in hydroxyproline-containing peptide levels in human plasma.

[2588] Proksch E et al. Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology. Skin Pharmacol Physiol 2014;27(1):47–55. . 2014. Link

[2593] Karim AA & Bhat R. Fish gelatin: properties, challenges, and prospects as alternative to mammalian gelatins. Food Hydrocolloids 2009;23(3):563–576. . 2009. Link

Review article (Food Hydrocolloids, 2009) on the properties, challenges, and prospects of fish gelatin as an alternative to mammalian gelatins.

[2594] Codex Alimentarius. General Standard for Food Additives — gelatin/collagen specifications.

Codex Alimentarius food additive standard (General Standard for Food Additives) setting out gelatin/collagen specifications.

[2595] EFSA Panel. Scientific Opinion on the safety of fish-derived collagen. EFSA Journal 2010. . 2010. Link

EFSA Panel scientific opinion (EFSA Journal, 2010) on the safety of fish-derived collagen.

[2596] Donaldson MS. Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements. Ann Nutr Metab 2000;44(5–6):229–234. . 2000. Link

BACKGROUND: Pure vegetarian diets might cause cobalamin deficiency due to lack of dietary intake. It was hypothesized that a population following a vegan diet consuming mostly raw fruits and vegetables, carrot juice, and dehydrated barley grass juice would be able to avoid vitamin B12 deficiency naturally. METHODS: Subjects were recruited at a health ministers' reunion based on adherence to the Hallelujah diet for at least 2 years. Serum cobalamin and urinary methylmalonic acid (MMA) assays were performed. Follow-up with sublingual tablets, nutritional yeast, or probiotic supplements was carried out on subjects with abnormal MMA results. RESULTS: 49 subjects were tested.

[2597] Watanabe F et al. Vitamin B12-containing plant food sources for vegetarians. Nutrients 2014;6(5):1861–1873. . 2014. Link

The usual dietary sources of Vitamin B12 are animal-derived foods, although a few plant-based foods contain substantial amounts of Vitamin B12. To prevent Vitamin B12 deficiency in high-risk populations such as vegetarians, it is necessary to identify plant-derived foods that contain high levels of Vitamin B12. A survey of naturally occurring plant-derived food sources with high Vitamin B12 contents suggested that dried purple laver (nori) is the most suitable Vitamin B12 source presently available for vegetarians. Furthermore, dried purple laver also contains high levels of other nutrients that are lacking in vegetarian diets, such as iron and n-3 polyunsaturated fatty acids. Dried purple laver is a natural plant product and it is suitable for most people in various vegetarian groups.

[2598] Pawlak R et al. The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12. Nutr Rev 2013;71(2):110–117. . 2013. Link

Journal article (Nutr Rev, 2013) examining the prevalence of cobalamin (vitamin B12) deficiency among vegetarians as assessed by serum vitamin B12.

[2599] Rizzo G et al. Vitamin B12 among vegetarians: status, assessment and supplementation2016;8(12):767. Nutrients. Link

Cobalamin is an essential molecule for humans. It acts as a cofactor in one-carbon transfers through methylation and molecular rearrangement. These functions take place in fatty acid, amino acid and nucleic acid metabolic pathways. The deficiency of vitamin B12 is clinically manifested in the blood and nervous system where the cobalamin plays a key role in cell replication and in fatty acid metabolism. Hypovitaminosis arises from inadequate absorption, from genetic defects that alter transport through the body, or from inadequate intake as a result of diet. With the growing adoption of vegetarian eating styles in Western countries, there is growing focus on whether diets that exclude animal foods are adequate.

[2600] Talbott S & Talbott J. Effect of BETA 1, 3/1, 6 GLUCAN on upper respiratory tract infection symptoms in marathon athletes. J Sports Sci Med 2009;8(4):509–515. . 2009. Link

A clinical trial (J Sports Sci Med) on the effect of BETA 1,3/1,6 GLUCAN on upper respiratory tract infection symptoms in marathon athletes. It evaluates beta-glucan supplementation and respiratory symptoms in athletes.

[2601] Choi HK et al. Purine-rich foods, dairy and protein intake, and the risk of gout in men. NEJM 2004;350(11):1093–1103. . 2004. Link

Journal article (NEJM, 2004) examining the association between purine-rich foods, dairy and protein intake, and the risk of gout in men.

[2602] Mokrowiecka A et al. ASCA, ANCA, ALCA, and AMCA antibodies as biomarkers in Crohn's disease. World J Gastroenterol 2009. . 2009.

Journal article (World J Gastroenterol, 2009) addressing ASCA, ANCA, ALCA, and AMCA antibodies as biomarkers in Crohn's disease.

[2603] EFSA Panel on Dietetic Products. Scientific Opinion on Saccharomyces cerevisiae as a food ingredient. EFSA Journal 2013. . 2013. Link

EFSA scientific opinion on the evaluation of Saccharomyces cerevisiae as a food ingredient (title-based; the specific content of the cited DOI/article could not be unambiguously confirmed from the search). Saccharomyces cerevisiae (brewer's yeast) is considered safe under EFSA's QPS (qualified presumption of safety) approach and is widely used as a food and food ingredient (e.g. yeast extract). Note: the search could not unambiguously identify the specific opinion behind the cited DOI; this description is based on the title and EFSA's general classification.

[2604] Goldberger J et al. The transmissibility of pellagra: experimental attempts at transmission to the human subject. Public Health Reports 1916. . 1916. Link

Classic experimental report by Joseph Goldberger and colleagues on the transmissibility of pellagra, in which they attempted to transmit the disease to human subjects (volunteers, including Goldberger himself and close associates) using nasal secretions, scabs, blood, urine and feces from pellagra patients (via ingestion and intramuscular/subcutaneous injection). None of the transmission attempts succeeded, supporting that pellagra is not an infectious disease (but is of nutritional origin).

[2605] Elvehjem CA et al. Relation of nicotinic acid and nicotinic acid amide to canine black tongue. J Am Chem Soc 1937;59:1767–1768. . 1937. Link

Landmark paper by Elvehjem and colleagues (Madden, Strong, Woolley) demonstrating the relation of nicotinic acid (and nicotinic acid amide) to canine "black tongue" — the canine equivalent of pellagra. Nicotinic acid and its amide, isolated from liver extract, cured black tongue (a single ~30 mg dose of nicotinic acid produced a marked response), thereby identifying niacin as the anti-pellagra vitamin.

[2606] Anderson RA et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes 1997;46(11):1786–1791. . 1997. Link

Chromium is an essential nutrient involved in normal carbohydrate and lipid metabolism. The chromium requirement is postulated to increase with increased glucose intolerance and diabetes. The objective of this study was to test the hypothesis that the elevated intake of supplemental chromium is involved in the control of type 2 diabetes. Individuals being treated for type 2 diabetes (180 men and women) were divided randomly into three groups and supplemented with: 1) placebo, 2) 1.92 micromol (100 microg) Cr as chromium picolinate two times per day, or 3) 9.6 micromol (500 microg) Cr two times per day. Subjects continued to take their normal medications and were instructed not to change their normal eating and living habits. HbA1c values improved significantly after 2 months in the group receiving 19.2 pmol (1,000 microg) Cr per day and was lower in both chromium groups after 4 months (placebo, 8.5 +/- 0.2\%; 3.85 micromol Cr, 7.5 +/- 0.2\%; 19.2 micromol Cr, 6.6 +/- 0.1\%).

[2607] Mertz W. Chromium in human nutrition: a review. J Nutr 1993;123(4):626–633. . 1993. Link

This review summarizes the results of 15 controlled studies supplementing defined Cr(III) compounds to subjects with impaired glucose tolerance. Three of these (3-4 mumol Cr/d for > 2 mo) produced no beneficial effects: serum glucose, insulin and lipid concentrations remained unchanged. The remaining 12 interventions improved the efficiency of insulin or the blood lipid profile of subjects (ranging from malnourished children and healthy middle-aged individuals to insulin-requiring diabetics). In addition, three cases of impaired glucose tolerance after long-term total parenteral alimentation responding to Cr supplementation have been reported. Chromium potentiates the action of insulin in vitro and in vivo; maximal in vitro activity requires a special chemical form, termed Glucose Tolerance Factor and tentatively identified as a Cr-nicotinic acid complex. Its complete structural identification is a major challenge to chromium research.

[2608] Weber G et al. Saccharomyces cerevisiae (CBS 5926) in acne vulgaris — clinical study. J Am Acad Dermatol 2012. . 2012.

Journal article reporting a clinical study (J Am Acad Dermatol, 2012) on Saccharomyces cerevisiae (CBS 5926) in acne vulgaris.

[2610] McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol 2010;16(18):2202–2222. . 2010. Link

This article reviews the evidence for efficacy and safety of Saccharomyces boulardii (S. boulardii) for various disease indications in adults based on the peer-reviewed, randomized clinical trials and pre-clinical studies from the published medical literature (Medline, Clinical Trial websites and meeting abstracts) between 1976 and 2009. For meta-analysis, only randomized, blinded controlled trials unrestricted by language were included. Pre-clinical studies, volunteer studies and uncontrolled studies were excluded from the review of efficacy and meta-analysis, but included in the systematic review. Of 31 randomized, placebo-controlled treatment arms in 27 trials (encompassing 5029 study patients), S. boulardii was found to be significantly efficacious and safe in 84\% of those treatment arms. A meta-analysis found a significant therapeutic efficacy for S. boulardii in the prevention of antibiotic-associated diarrhea (AAD) (RR = 0.47, 95\% CI: 0.35-0.63, P < 0.001). In adults, S. boulardii can be strongly recommended for the prevention of AAD and the traveler's diarrhea.

[2612] Anderson MC et al. Tyramine reactions and the cheese effect: MAO-inhibitor interactions. J Clin Psychiatry 1993. . 1993.

Journal article (J Clin Psychiatry, 1993) addressing tyramine reactions and the "cheese effect," i.e., interactions with MAO inhibitors.