2. Spirulina
The "blue-green super-protein" — phycocyanin pigment, 60% plant protein, and NASA-cohort evidence.
Spirulina in 1 minute
What does it provide? Cyanobacteria-derived complete protein, phycocyanin pigment (antioxidant), GLA, and β-carotene — with anti-inflammatory, lipid- and glucose-modulating effects.
How much? 1–5 g/day in powder or tablet form — start low (1 g), increase gradually. Most clinical trials used 1–8 g/day.
When to avoid? Phenylketonuria (PKU — phenylalanine content), autoimmune disease flare (immunostimulant), anticoagulant therapy, spirulina of unknown (wild) origin (cyanotoxin, heavy-metal contamination). Never consume unverified, "natural pond" spirulina.
Spirulina is technically not an alga but a filamentous cyanobacterium — evolutionarily closer to bacteria than to plants. Despite this, it served for thousands of years as a traditional food in two separate cultures: the Aztecs gathered it from the surface of Mexico's Lake Texcoco under the name "tecuitlatl," and sold it as sun-dried cakes in the markets of Tenochtitlan — already described by the 16th-century chronicler Bernardino de Sahagún. In Africa, around Lake Chad, the Kanembu people consume it to this day under the name "dihé," drying it on clay tablets and mixing it into millet stews and sauces.
The scientific "rediscovery" began in 1940, when French botanist Pierre Dangeard documented the use around Lake Chad, and then after Belgian botanist Jean Léonard's 1964 expedition, the French Institut Français du Pétrole launched indoor cultivation research. In the 1970s, NASA considered it as astronaut food (due to its high protein-to-volume ratio), and the 1974 UN World Food Conference called it "the best food of the 21st century." From the 2000s onward, it became a main player in the dietary supplement industry, while WHO and IIMSAM (a UN observer-status organization) study it as a tool against childhood malnutrition from India to Burkina Faso.[2180]
Scientific Background
60–70% of spirulina's dry matter is protein, containing all essential amino acids — although methionine and cysteine content is lower than in animal proteins. Digestibility is excellent (PDCAAS ≈ 0.7–0.8) because the cell wall is a thin peptidoglycan layer (not cellulose as in chlorella) — therefore it is absorbable without cooking or cell-wall disruption.
Phycocyanin is spirulina's blue pigment (10–15% of the protein content), a strong antioxidant and COX-2 inhibitor based on in vitro and animal data. Human RCT meta-analyses (Serban 2016, Hamedifard 2019) documented moderate LDL (≈ –10–15 mg/dL), TG, and blood-pressure reduction at 1–10 g/day doses, in 8–12-week interventions.[2177][2178] Data on NAFLD and HbA1c are promising but weaker.[2179]
B12 issue — critical myth zone: spirulina contains pseudo-B12-like corrinoids (mainly adenosyl-pseudocobalamin), which, however, are not active in the human metabolic system — moreover, some studies suggest they may competitively block the absorption of genuine B12. Watanabe (1999, 2007) clearly states: spirulina is NOT a B12 source for vegans — pseudo-B12 is inactive in the human body.[2175][2176]
At the microbiome level, human data are limited: animal experiments and a few small human studies showed Lactobacillus and Bifidobacterium proportions increasing while Enterobacteriaceae decreased. Phycocyanin, on reaching the colon, ferments in a polyphenol-like manner. Spirulina polysaccharides (calcium-spirulan, immulina) are immunomodulating.[2182]
Contamination risk: wild spirulina may contain microcystin (a hepatotoxic cyanotoxin) due to other cyanobacterial contamination. Controlled indoor or closed-system cultivation (Hawaii, California, Greece, Taiwan) minimizes this. Heavy-metal accumulation (lead, arsenic, mercury) is also quality-dependent — a third-party-tested product from a quality manufacturer is essential.[2181]
- + Vitamin C-rich matrix (lemon, tomato, orange): increases the bioavailability of iron and phycocyanin; stabilizes polyphenols against oxidation.
- + Healthy fat (avocado, olive, flaxseed): carotenoids (β-carotene, zeaxanthin) are fat-soluble — eaten together increases absorption.
- + Polyphenol sources (green tea, cacao, berries): combined antioxidant synergy, phycocyanin stabilization.
- + Live cultures (kefir, yogurt, sauerkraut): synbiotic effect — spirulina polysaccharides and probiotic strains together strengthen microbiome modulation.
- + Fiber-rich matrix (oats, flaxseed, legumes): the combination of spirulina protein + soluble fiber yields a more stable glucose response than either alone.
- + B12-containing source (nori, egg, meat, or supplement): NEVER consider spirulina as B12 replacement — always supplement with a genuine source.
- Immunosuppressants (cyclosporine, tacrolimus, mycophenolate, biologics — TNF inhibitors, IL-17/23 inhibitors): spirulina is immunostimulating (NK-cell and macrophage activation) — autoimmune flare and weakening of therapeutic effect possible.
- Anticoagulants (warfarin, DOACs), antiplatelets: γ-linolenic acid (GLA) and some phycocyanin fractions have weak antiplatelet activity — additive bleeding risk at high doses.
- Iron supplementation (capsule, drops): separate timing by ≥ 2 hours — chlorophyll and some spirulina proteins can chelate.
- Phenylalanine-containing medications or aspartame-containing drinks (in PKU patients): spirulina contains significant phenylalanine (≈ 4–5% dry matter).
- Cold drink + raw powder: the powder clumps, unpleasant texture — mix into warm or room-temperature smoothies, or first make a paste with a little liquid.
- Empty stomach + high dose (≥ 5 g) on first occasion: nausea, vomiting possible — start with a meal.
- Phenylketonuria (PKU): spirulina contains ≈ 4–5% phenylalanine — absolute contraindication.
- Autoimmune disease active flare (SLE, RA, MS, IBD, psoriasis active phase): due to the immunostimulant effect, it can worsen — in remission only after medical consultation.
- Wild spirulina of unknown origin: microcystin contamination can lead to liver damage — never consume pond, unverified product.
- Thyroid disease with iodine sensitivity: spirulina's iodine content is low (negligible compared to sea algae), but products from quality manufacturers are preferred.
- Gout, high uric acid level: the high protein and purine content (especially relative to dry matter) can provoke a flare — try with a low dose (1 g), or avoid.
- Kidney disease (chronic, GFR < 60): the high protein load is to be avoided — medical consultation.
- Pregnancy and breastfeeding: culinary-dose (1–2 g/day) spirulina from a verified source is likely safe, but high-dose supplementation is to be avoided — little human data.
- 2 weeks before surgery: stop high doses (bleeding risk).
Daily serving: 1–5 g/day powder or 2–10 tablets of 500 mg. Start with 1 g, increase to 2–3 g after 1 week.
Preparation pattern:
- Smoothie: 1–3 g powder + 1 banana + 200 ml plant milk + 1 pinch of lemon zest + 1 tbsp almond butter — blend. Lemon and fat together improve bioavailability.
- Energy bar: dates + rolled oats + almond + 2 g spirulina powder + cacao — pressed into a mold, chilled.
- Salad dressing: 1 g powder + olive oil + lemon juice + Dijon mustard + salt — homogeneous, intense green dressing.
- Tablet: with a meal, 2–4 in the morning, 2–4 in the evening — first time start with a low dose.
Storage: airtight, dark glass, in a cool place — phycocyanin is light- and heat-sensitive. To be consumed within 6 months of opening. Do NOT store in a warm, humid place.
What not to do: don't cook it (≥ 60 °C destroys phycocyanin and reduces amino-acid quality). Don't buy from unknown sources. Don't use as a B12 replacement.
References
[2175] Watanabe F. Vitamin B12 sources and bioavailability. Exp Biol Med 2007;232(10):1266–1274. . 2007. 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).
[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.