Blue-green alage

Blue-Green Algae (Cyanobacteria): A Comprehensive Reference

1. Identity: Taxonomy, Nomenclature, and Common Forms

Blue-green algae are actually a type of bacteria known as cyanobacteria. The common name arose because of the characteristic color — a by-product of photosynthetic pigmentation — and their discovery as an algal-like scum on the surface of ponds. They were assumed to be algae until their true identity as prokaryotic bacteria was established. Earlier literature used the term "blue-green algae" to refer to a group of microorganisms possessing chlorophyll and appearing blue-green in color, but modern microbiology has distinguished these organisms from eukaryotic algae and classified them more appropriately as cyanobacteria, since their cell architecture more closely resembles prokaryotic bacteria.

Blue-green algae (BGA), also known as cyanobacteria, are among the photosynthetic prokaryotes found in aquatic ecosystems. The species most widely consumed by humans include Aphanizomenon flos-aquae (AFA), Spirulina platensis (SP), Spirulina maxima (SM), Spirulina fusiformis (SF), and Nostoc commune var. sphaeroids Kutzing (NO). Human consumption of SP is traced back to the 14th-century Aztec civilization, while the earliest human use of NO was recorded 1,600 years ago in China.

Spirulina is a microscopic and filamentous cyanobacterium that derives its name from the spiral or helical nature of its filaments. It has a long history of use as food and has been reported in the Aztec civilization. Spirulina refers to the dried biomass of Arthrospira platensis, an oxygenic photosynthetic bacterium found worldwide in fresh and marine waters. Among the many varieties of spirulina, the most commonly studied species are Spirulina platensis (Arthrospira platensis), Spirulina maxima (Arthrospira maxima), and Spirulina fusiformis (Arthrospira fusiformis). Spirulina grows naturally in high-salt alkaline water reservoirs in subtropical and tropical areas of America, Mexico, Asia, and Central Africa.

Spirulina species are cultured in alkaline fresh water, whereas Aphanizomenon flos-aquae (AFA) is naturally grown and harvested from Upper Klamath Lake, Oregon, USA. Although the recognition of the bacterial nature of these microbes is relatively recent, cyanobacteria are ancient organisms. Fossils of cyanobacteria have been found dating back 3.5 billion years, making them among the oldest fossils of any life form thus far discovered on Earth.

Common Forms and Preparations

Blue-green algae food supplements (BGAS) are easily available and widespread, sold as nutraceuticals over the counter in pharmacies, supermarkets, and herbalists, as well as over the internet. They are prepared in a variety of forms: tablets, powder, capsules, and besides algae (dried or extracts in various combinations). Blue-green algae products usually contain either AFA-algae (Aphanizomenon flos-aquae) or Spirulina species, or both. Spirulina was acknowledged by the US FDA as a legally marketed food in 1981 and is currently consumed in the US as a dietary supplement at doses of 3 to 4.5 grams per day.

2. Traditional and Historical Use

Although blue-green algae has only recently surged in popularity in Western health circles, cultures have been consuming it for hundreds of years. In Central Mexico, Spanish chroniclers described Aztec fishermen living around Lake Texcoco collecting blue-green algae, which they called tecuitlatl, and adding it to roasted corn and tortillas. Central-African women living around Lake Chad still collect spirulina, which they form into sun-dried cakes called dihé.

The botanist Jean Léonard came across curious blue-green cakes in native markets of Fort Lamy (now Ndjemena) in Chad. When locals said these cakes came from areas near Lake Chad, Leonard recognized the connection between algal blooms and the dried cakes sold in the market. He observed that 70 percent of the food of the Kanembu was accompanied by a sauce made with these dried cakes. Techniques of harvesting and drying have been passed from mother to daughter for generations. When the rains stop, Kanembu women scoop the wet algae in clay pots, drain the water through bags of cloth, and spread the algae on a circular sand filter to dry in the sun.

Spirulina (Arthrospira platensis) is a blue-green microalga with a long history as a food source in East Africa and pre-colonial Mexico. The earliest human use of Nostoc commune var. sphaeroids was recorded 1,600 years ago in China, where it was used both as food and in medicine. Spirulina's use as a dietary staple dates back to the 16th century, when Aztec peoples consumed it as part of their diet.

3. Key Constituents and Active Compounds

Macronutrient and Micronutrient Profile

Dried spirulina typically contains 60–70% protein, 15–20% carbohydrates, 5–8% lipids, vitamins, minerals, essential fatty acids, β-carotene, and the rare essential γ-linolenic acid. It is an excellent source of proteins, vitamins (ascorbic acid, tocopherol, and B-complex), minerals (iron and magnesium), and fatty acids (gamma-linolenic acid, capric acid, palmitic acid, omega-3 and omega-6). Spirulina is a good source of high-quality protein (about 60–70% of its dry weight), containing all the essential amino acids. Due to the absence of cellulose in its cell wall, the protein in spirulina is absorbed at an efficiency of up to 90%.

It is often claimed that spirulina contains vitamin B12, but this is not accurate. It contains pseudovitamin B12, which has not been shown to be effective in humans.

Phycocyanin and Phycobiliproteins

Phycocyanin itself is made up of proteins and pigments called phycobiliproteins and phycocyanobilins. These give it its characteristic color and contribute to the photosynthesis necessary for cyanobacteria. Phycocyanin captures light energy which, through a series of reactions, is converted into organic matter. The antioxidant activity of spirulina has been shown to be directly proportional to the quantity of phycocyanin (which contains phycocyanobilin).

C-phycocyanin (C-PC) is one of the major biliproteins of spirulina with antioxidant and radical scavenging properties. C-PC, a selective cyclooxygenase-2 (COX-2) inhibitor, induces apoptosis in lipopolysaccharide-stimulated macrophages. It is also known to exhibit anti-inflammatory and anticancer properties.

Other Bioactive Compounds

In addition to its high protein content, spirulina has a high concentration of bioactive compounds, such as phenols, phycocyanin pigment, and polysaccharides, which all take part in a number of biological activities, including antioxidant and anti-inflammatory activity. Spirulina contains phytopigments (carotenoids and phycocyanins) and bioactive compounds (polyphenols and flavonoids), which have a wide range of biological activities, including antimicrobial, hypolipidemic, hypocholesterolemic, antioxidant, and anti-inflammatory effects.

Spirulina contains a set of specific molecules — c-phycocyanin, complex polysaccharides such as calcium spirulan, and γ-linolenic acid — which have strong prophylactic and therapeutic potential, especially in the fields of cardiovascular diseases, viral infections, cancer prevention and therapy, immune response, as well as diabetes and cholesterol control.

The AFA extract known as Klamin® is particularly rich in β-phenylethylamine (β-PEA), a trace-amine considered a neuromodulator in the central nervous system.

Mechanisms of Action

BGA contain various bioactive components, such as phycocyanin, carotenoids, γ-linolenic acid, fibers, and plant sterols, which can promote optimal health in humans. Studies have demonstrated that several BGA species or their active components have plasma total cholesterol and triglyceride-lowering properties due to their modulation of intestinal cholesterol absorption and hepatic lipogenic gene expression. BGA can also reduce inflammation by inhibiting nuclear factor κB (NF-κB) activity, consequently reducing the production of proinflammatory cytokines. Furthermore, BGA inhibit lipid peroxidation and have free radical scavenging activity, which can be beneficial for protection against oxidative stress.

The proposed mechanism of action of spirulina for weight management includes reduction of macrophage infiltration into visceral fat, prevention of hepatic fat accumulation, reduction in oxidative stress, improvement in insulin sensitivity and satiety. Reduction in appetite may be due to an improvement in leptin resistance in the arcuate nucleus. One of the components of spirulina, glycolipid H-b2, inhibits pancreatic lipase activity in a dose-dependent way, thus reducing postprandial triglyceride levels.

Spirulina exhibits anti-inflammatory properties, in particular, by inhibiting histamine release from mast cell-mediated allergic reactions. The active ingredient found in spirulina responsible for its anti-inflammatory activities is C-phycocyanin, a pigment commonly found in blue-green algae. C-phycocyanin can selectively inhibit the activity of cyclooxygenase-2 (COX-2), an enzyme responsible for prostaglandin biosynthesis.

4. Scientific Evidence by Area of Use

4.1 Cardiovascular Health: Lipid Profiles

A systematic review published in 2015 encompassing eight human studies concluded that spirulina has blood lipid-lowering benefits and antioxidant effects. A 2018 meta-analysis of 12 clinical studies in humans showed that spirulina supplementation (1 g up to 19 g per day) significantly lowered total cholesterol (−36.60 mg/dL; p=0.0001), LDL cholesterol (−33.16 mg/dL; p=0.0002), triglycerides (−39.2 mg/dL; p=0.0001), very-low-density lipoprotein cholesterol (−8.02 mg/dL; p=0.0001), fasting blood glucose (−5.01 mg/dL; p=0.04), and diastolic blood pressure (−7.17 mmHg; p=0.001).

Based on available literature, one meta-analysis revealed a significant benefit of spirulina supplementation in improving multiple markers of cardiovascular health including total cholesterol, LDL-C, triglycerides, vLDL-C, fasting blood glucose, and diastolic blood pressure, without any significant side effects. Spirulina is generally used as a nutraceutical food supplement due to its nutrient profile, lack of toxicity, and therapeutic effects. Clinical trials have investigated the influence of spirulina on metabolic-related risk factors but have yielded conflicting results in humans.

In patients with type 2 diabetes, subjects who consumed 2 g/day of spirulina for 2 months showed significantly lower plasma triglyceride concentrations as well as a significant reduction in ratios of total cholesterol:HDL-C and LDL-C:HDL-C. Eight grams per day of spirulina supplementation for 12 weeks significantly reduced plasma triglyceride concentrations and blood pressure in type 2 diabetic patients with higher initial triglyceride levels, whereas subjects with high initial total cholesterol and LDL-C showed significant reductions in plasma lipids.

Evidence strength: The evidence for lipid-lowering effects is moderate. Multiple RCTs and meta-analyses support the finding, but trials are often small, short-term, and heterogeneous in population and dosage. Results are not consistent across all study groups.

4.2 Blood Pressure

A GRADE-assessed systematic review and meta-analysis of RCTs found that spirulina consumption decreases systolic blood pressure (SBP) (WMD: −4.41 mmHg, 95% CI: −6.74 to −2.07, I² = 66.1%) and diastolic blood pressure (DBP) (WMD: −2.84 mmHg, 95% CI: −4.65 to −1.03, I² = 62.3%). Subgroup analysis demonstrated SBP and DBP were still lower in individuals with ≥120/≥80 mmHg, hypertensive individuals, overweight individuals, those over age 50, and in interventions lasting more than 8 weeks. The authors noted no publication bias, but based on GRADE, outcomes had only moderate quality.

The impact of spirulina intake on blood pressure has been evaluated in several randomized clinical trials. A randomized, triple-blind, placebo-controlled trial conducted on 48 hypertensive patients assessed the effects of consuming a salad dressing enriched with 2 g/day of spirulina powder over 8 weeks. The results showed a significant reduction in both systolic (p = 0.02) and diastolic (p = 0.01) blood pressure.

One study demonstrated benefits of Spirulina maxima in 40 hypertensive patients without cardiovascular disease when supplemented with 2 g of spirulina per day versus placebo for 3 months. In those given spirulina, there was a significant reduction in BMI (26.9±3.1 vs. 25.0±2.7 kg/m²; p=0.0032), weight (75.5±11.8 kg vs. 70.5±10.3 kg; p<0.001), systolic blood pressure (149±7 mmHg vs. 143±9 mmHg; p=0.0023), and arterial stiffness index (7.2±0.6 vs. 6.9±0.7 m/s; p<0.001).

In contrast, one clinical investigation did not observe any significant effects of spirulina supplementation on blood pressure in healthy subjects compared to placebo. Subjects consumed four capsules of 4.8 g spirulina or a placebo after breakfast, lunch, and dinner for 17 days.

Evidence strength: Moderate. Blood-pressure effects appear most consistent in hypertensive rather than normotensive individuals, and interventions of longer duration (>8 weeks) appear more likely to yield significant results. High heterogeneity (I² >60%) is a limitation across meta-analyses.

4.3 Blood Glucose and Diabetes Management

The efficacy of blue-green algae in reducing lipid levels in type 2 diabetes mellitus (T2DM) has been evaluated in clinical trials. One study examined the simultaneous action of metformin therapy and 2 g/day spirulina in diabetic patients for 12 weeks. Supplementation of S. platensis before meals was shown to have a hypolipidemic action and to be a valuable adjunct to metformin therapy.

Research demonstrates that spirulina, as an adjunct to metformin, outperforms metformin alone in long-term blood glucose and lipid control in T2DM patients, without significant adverse effects or hepatic or renal complications.

Evidence strength: Preliminary to moderate. Several small clinical trials and meta-analyses report beneficial effects on fasting blood glucose and HbA1c, particularly in those with existing metabolic dysfunction. Larger, longer-duration RCTs are needed.

4.4 Weight Management and Body Composition

Meta-analytic findings indicate that spirulina significantly reduces body weight (effect size g = −0.30, approximately 2.36 kg), representing approximately 2–3% of initial body weight. While this reduction may not meet the 5–10% threshold required for substantial cardiovascular risk reduction in obese patients, modest weight loss may still confer meaningful health benefits. A systematic review suggests that weight loss below 5% can still improve cardiovascular, metabolic, and quality-of-life outcomes.

Evidence strength: Modest. The weight loss effect is statistically significant but clinically modest. Individual study quality varies, and blinding is often limited in supplement trials.

4.5 Allergic Rhinitis and Immune Modulation

Spirulina has the ability to modulate immune functions and exhibits anti-inflammatory properties by inhibiting the release of histamine by mast cells. In a randomized, double-blind, placebo-controlled trial, individuals with allergic rhinitis were fed daily either with placebo or spirulina for 12 weeks. Peripheral blood mononuclear cells were isolated before and after spirulina feeding, and cytokine levels (interleukin-4, IFN-γ, and interleukin-2) were measured. The study showed that a high dose of spirulina significantly reduced IL-4 levels by 32%, demonstrating a protective effect toward allergic rhinitis.

In a double-blind, placebo-controlled study from Turkey evaluating the effectiveness and tolerability of spirulina in treating patients with allergic rhinitis, spirulina consumption significantly improved symptoms and physical findings compared with placebo (p < .001), including nasal discharge, sneezing, nasal congestion, and itching.

A Japanese team identified the molecular mechanism of the human immune capacity of spirulina by analyzing blood cells of volunteers before and after oral administration of a hot water extract of Spirulina platensis. IFN-γ production and natural killer (NK) cell cytotoxic activity were increased after administration of the microalga extracts to male volunteers.

In healthy humans, AFA-algae appear to increase blood levels of natural killer cells, a type of immune cell.

Evidence strength: Moderate for allergic rhinitis specifically. Two well-controlled clinical trials show benefit in rhinitis patients. Immunomodulatory findings are consistent but further large-scale clinical confirmation is needed.

4.6 Antioxidant Effects

In a randomized, double-blind, placebo-controlled study, the antioxidant capacity, immunomodulatory, and lipid-lowering effects of spirulina administered at a dose of 8 g/day for 16 consecutive weeks in healthy elderly subjects were evaluated. BGA inhibit lipid peroxidation and have free radical scavenging activity, which can be beneficial for the protection against oxidative stress.

Evidence strength: The antioxidant mechanisms are well-established in laboratory and animal models; clinical evidence in humans is suggestive but limited by study size and outcome diversity.

4.7 Brain Health and Neuroprotection

Spirulina microalgae contain a plethora of nutrient and non-nutrient molecules providing brain health benefits. Numerous in vivo studies have provided support for the brain health potential of spirulina, highlighting antioxidant, anti-inflammatory, and neuroprotective mechanisms. Preliminary clinical studies have suggested that spirulina can help to reduce mental fatigue, protect the vascular wall of brain vessels from endothelial damage, and regulate internal pressure, thus potentially contributing to prevention or mitigation of cerebrovascular conditions.

The AFA extract Klamin®, containing β-phenylethylamine (PEA), is notable for its mental health benefits, particularly in alleviating depression and anxiety, and shows promise in ADHD treatment and neurodegenerative disease management.

Evidence strength: Preliminary. Most neuroprotective evidence remains at the in vitro and animal level. Human clinical data are limited and consist largely of small pilot studies. More rigorous trials are needed before clinical conclusions can be drawn.

4.8 Antiviral Activity

In laboratory experiments, calcium spirulan, an extract from spirulina, stopped the doubling of HIV virus, herpes simplex virus, cytomegalovirus, and influenza virus, but it is not known whether any of these effects would occur in the human body.

Evidence strength: Preclinical only. All antiviral data presently derive from in vitro experiments. No completed human clinical trials have confirmed antiviral efficacy.

4.9 Cancer Prevention

Blue-green algae have not been shown to treat or prevent cancer, AIDS, attention deficit hyperactivity disorder (ADHD), or other serious medical conditions in human clinical trials. Studies have shown that spirulina protected lab animals from genetic mutations caused by chemicals and radiation, but it remains unclear whether these effects occur in humans.

Evidence strength: Weak to absent for human applications. Animal and in vitro data suggest chemopreventive potential, but no robust clinical evidence currently supports the use of blue-green algae for cancer treatment or prevention in humans.

4.10 Liver Health

In controlled trials, spirulina has not been linked to serum enzyme elevations or to instances of clinically apparent liver injury. In several studies, serum aminotransferase levels have decreased with spirulina therapy, and it has been evaluated in uncontrolled studies as a potential treatment of nonalcoholic steatohepatitis.

Evidence strength: Preliminary and largely based on uncontrolled studies. The use of spirulina in nonalcoholic fatty liver disease is investigational.

5. Body Systems and Health Areas of Association

• Cardiovascular system: Lipid-lowering, blood pressure reduction, endothelial protection
• Metabolic/endocrine system: Glycemic control, insulin sensitivity, weight management
• Immune system: NK cell activation, IgA production, histamine modulation, allergic rhinitis symptom relief
• Nervous system: Antioxidant neuroprotection, β-PEA-mediated neuromodulation (AFA), mental fatigue reduction
• Hepatic system: Aminotransferase reduction, potential role in NASH (investigational)
• Gastrointestinal system: In rats with colitis, oral gavage of 2 g/kg spirulina for 7 days decreased inflammation in mucosa and submucosa and tissue malondialdehyde (MDA) levels, suggesting spirulina may be beneficial for preventing inflammatory bowel disease. Human data are lacking.

6. Dosage Forms and Dosages Reported in Studies

Blue-green algae can be taken as a powder, flakes, capsules, or tablets. The typical manufacturer's recommended intake is 2,000–3,000 mg per day, divided throughout the day.

Spirulina is currently consumed in the US as a dietary supplement at doses of 3 to 4.5 grams per day. Spirulina doses of 10 to 19 grams per day over several months have been used safely in clinical research settings.

Specific dosages used in clinical trials and reviews include:

• 2 g/day for 2 months in type 2 diabetes patients (lipid outcomes); 8 g/day for 12 weeks in type 2 diabetes patients (triglycerides and blood pressure).
• 2 g/day over 8 weeks in 48 hypertensive patients (blood pressure outcomes).
• Four capsules of 0.5 g spirulina maxima each (total 2 g/day) in 40 hypertensive patients over 3 months.
• 8 g/day for 16 consecutive weeks in healthy elderly subjects (antioxidant and immunomodulatory outcomes).
• Range of 1 g to 19 g per day across 12 human clinical studies included in a 2018 meta-analysis of lipid and metabolic markers.

7. Safety Considerations and Documented Interactions

General Safety

The safety of spirulina has been established through centuries of use as a food and numerous toxicology studies. Acute, subchronic, and chronic toxicology, teratogenicity, and mutagenicity studies have shown no toxic effects. Spirulina supplements are regarded as "possibly safe," provided they are free of microcystin contamination, and "likely unsafe" (especially for children) if contaminated.

Microcystin Contamination

Many cyanobacteria are known to produce various cyanotoxins, and blue-green algae dietary supplements (BGASs) have long been suspected of containing toxic cyanobacteria and cyanotoxins. Among the hepatotoxins, microcystins (MCs) are hepatotoxic and cyclic heptapeptides, of which there are more than 270 congeners. These toxic compounds are not produced by spirulina itself, but can occur if spirulina batches are contaminated with other, toxin-producing, blue-green algae.

In a study examining 17 brands on the Italian market, samples containing spirulina only were free of contamination. However, the Aphanizomenon flos-aquae-based samples were contaminated by highly variable levels of microcystins (MC-LR and MC-LA congeners), up to 5.2 μg MC-LR equivalents per gram of product. The highest variability (up to 50-fold) was among batches of the same brand.

A 2016 review by Health Canada found that spirulina products contained varying levels of microcystins. Health Canada restricts microcystin-LR levels in products containing cyanobacteria to 0.02 μg per kilogram of body weight per day in finished products, or a maximum of 1 part per million in raw materials.

The biotoxins microcystin and nodularin have been implicated in causing irreversible hepatotoxicity and tumor-promoting reactions in laboratory rats. Evidence from China suggests a correlation between microcystins in drinking water and primary liver cancer.

Heavy Metal Contamination

Heavy-metal contamination of spirulina supplements has raised concern. The Chinese State Food and Drug Administration reported that lead, mercury, and arsenic contamination was widespread in spirulina supplements marketed in China. One study reported the presence of lead up to 5.1 ppm in a commercial supplement sample. Because blue-green algae can accumulate heavy metals from contaminated water, consuming blue-green algae could increase the body's load of lead, mercury, and cadmium.

Public-health researchers have raised the concern that consumers cannot be certain that spirulina and other blue-green algae supplements are free of contamination.

Hepatotoxicity

Spirulina has been implicated in isolated case reports in causing clinically apparent liver injury, but the role of spirulina as opposed to other herbal components or contaminants has not been established. Liver injury due to spirulina must be very rare, if it occurs at all. The severity of liver injury in reports of spirulina hepatotoxicity has varied from mild, asymptomatic elevations in serum enzymes to self-limiting, clinically apparent hepatitis. There have been no reports of acute liver failure, chronic hepatitis, or vanishing bile duct syndrome attributed to spirulina.

Phenylketonuria (PKU)

Like all protein-rich foods, spirulina contains the essential amino acid phenylalanine, which is relevant for individuals with phenylketonuria (PKU), who are unable to metabolize this amino acid normally.

Drug Interactions

At the time of published reviews, there were no well-known supplement or food interactions with this supplement, and no reported interactions between spirulina/blue-green algae and medicines were identified in the reviewed literature. It is possible that unknown interactions exist. Given spirulina's demonstrated effects on blood lipids, blood glucose, and blood pressure, theoretical interactions with antidiabetic drugs, antihypertensive agents, and lipid-lowering medications are clinically plausible, though they remain unstudied in controlled interaction trials.

Bacterial Contamination

Several potentially pathogenic bacteria, including Bacillus cereus and Klebsiella pneumoniae, have been detected in spirulina products. Microcystin toxins were detected in all products at levels that could lead consumers to exceed recommended daily limits. The study showed that there are microbiological safety issues associated with commercial spirulina products, most likely associated with the normal means of production in open ponds.

References

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