1. Broccoli sprout

The sulforaphane concentrate — 50–100× the sulforaphane of mature broccoli, and chemopreventive RCTs.

Broccoli sprout in 1 minute

What does it provide? One of nutrition science's strongest natural NRF2-activator sources — a sulforaphane concentrate, providing 10–100× the mature broccoli amount per unit mass (Fahey 1997, Johns Hopkins).

How much? 30–100 g fresh sprouts daily (1–3 handfuls) — 20–60 mg sulforaphane equivalent. Most effective fresh and CHEWED (the myrosinase activates).

When to avoid? Thyroid disease (Hashimoto's, iodine deficiency) in large amounts — capsule-level doses to be avoided. Salmonella/E. coli risk: in pregnancy, infants, immunocompromised, only home-sprouted with verified hygiene. Anticoagulant + capsule dose.

Scientific Background

The broccoli sprout (3–5 days) is a glucoraphanin (a thioglucosinolate) concentrate — its content per fresh mass is 10–100× that of mature broccoli. Glucoraphanin alone is inactive; bioactivation occurs by two routes:

1. Plant myrosinase enzyme (released on chewing, if NOT heat-treated) → sulforaphane (an isothiocyanate).
2. Colonic microbiome myrosinase activity (especially Bacteroides thetaiotaomicron) — even cooked broccoli sprouts are partially converted to sulforaphane.

Sulforaphane is the most potent natural NRF2-Keap1 activator. NRF2 (Nuclear factor erythroid 2-related factor 2) is the master transcription factor for the cell's endogenous antioxidant and detoxification enzymes — activation initiates systemic protective effects:

• Glutathione-S-transferase (GST) synthesis ↑
• NAD(P)H quinone oxidoreductase 1 (NQO1) ↑
• Heme oxygenase-1 (HO-1) ↑
• Glutathione synthesis ↑

Clinical evidence:

• NAFLD: Kikuchi (2015) RCT, broccoli sprout extract over 60 days reduced ALT and hepatic fat content in T2DM-NAFLD patients [2526].
• Autism spectrum symptoms: Singh (2014, PNAS) RCT with 40 young men, 18 weeks broccoli sprout extract reduced behavioral symptoms; replication in small studies ongoing [2527].
• Helicobacter pylori: Yanaka (2009), 4 weeks of sprout consumption reduces H. pylori colonization — moderate evidence [2528].
• Airway antioxidant status: Riedl (2009), airway GST activity improvement, promising for asthma patients (small studies) [2529].
• Oxidative stress biomarkers: multiple RCTs confirmed 8-OH-dG, MDA reduction.
• Chemoprevention: epidemiology promising (Brassica consumption vs. colon, prostate, breast cancer), causal evidence experimental.

Sulforaphane content depends on day of germination, temperature, and light exposure — 3-day sprouts are optimal (Fahey 1997) [2532]. COOKING denatures myrosinase, but microbiome bioactivation partially compensates. Fresh, CHEWED sprouts give the highest sulforaphane activity.

Thyroid risk (goitrogenic potential) is documented at industrial capsule doses — dietary amounts in an iodine-adequate diet are safe.

References

[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

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).

[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.