Spirulina (Blue-Green Algae) as an Antiviral, Antineoplastic, and Anti-inflammatory Agent
Spirulina (Blue-Green Algae) as an Antiviral, Antineoplastic, and Anti-inflammatory Agent
June 2001; Volume 4; 67-70
By Robert J. Nardino, MD, FACP
Is it possible to eat pond scum and feel better? a rich source of protein, carotenoids, and other micronutrients, blue-green algae products have been consumed by man for hundreds, if not thousands, of years. Current interest in blue-green algae, the best known of which is spirulina, began with reports of its nutritional value and more recently reflects its potential therapeutic role.
Spirulina and other chlorophyll-containing products also are known as green foods with many health effects, ranging from fostering increased energy and improved mood to curing virtually every known disease. Spirulina in particular is aggressively marketed. Are there any supporting data?
Biology
As it turns out, blue-green algae are not really algae, but a subgroup of photosynthetic bacteria known as cyanobacteria. Found in a variety of aqueous environments, cyanobacteria inhabit places as diverse as freshwater lakes, brackish marshes, and thermal hot springs.
Cyanobacteria are the only organisms able to fix both carbon dioxide and nitrogen. Products sold for commercial consumption as blue-green algae contain predominantly Spirulina species, particularly S. maxima and S. platensis, as well as non-Spirulina species such as Aphanizomenon flos-aquae. Much of the commercial blue-green algae is grown under controlled conditions, although some, especially Aphanizomenon, are harvested from their natural setting.
Nutritional Information
Spirulina consists of approximately 65% crude protein. A rich source of beta-carotene, spirulina is touted as having high concentrations of B vitamins, particularly B12; it is marketed to vegans as a reliable source of this vitamin. The B12 it contains, however, appears to be predominantly cobalamin analogues that are not bioavailable to humans. In one study of B12-deficient children, serum B12 levels rose after the kids were fed spirulina, but there was no effect on hematopoiesis.1 A recent analysis found the majority of the vitamin B12 concentration in spirulina, as measured by two different assays, to be inactive. However, a small fraction was able to bind intrinsic factor. This minute active fraction was characterized to be 83% pseudovitamin B12 and 17% cobalamin.2 Therefore, there may be a small amount of active B12 available in spirulina. Iron and other minerals are abundant, with as much as 1.5-2 mg of iron available in 10 g of dry spirulina. There also is a significant concentration of the amino acid phenylalanine.
In Vitro and Animal Studies
Some Cyanobacteria species appear to have antiretroviral activity. Most studies have used in vitro systems to examine this effect, but animal studies also have found evidence of activity. Most studies have utilized cyanobacteria distinct from those that are used commercially.3,4 The main effect appears to be inhibition of reverse transcriptase by sulfated homopolysaccharides extracted from cyanobacteria.
One well-publicized laboratory study employed Spirulina platensis. An extract from this spirulina, called cyanovirin-N, inhibited HIV infection of peripheral blood mononuclear cells in vitro.5 The results of this study figure prominently on the web sites of many distributors, though the clinical implications of this finding have yet to be determined.
In vitro studies also have identified components isolated from cyanobacteria capable of exerting antioxidant and anti-inflammatory effects, and have demonstrated the ability to overcome multiple drug resistance in tumor cells.6,7 Extracts from Oscillatoria and Synechocystis species, but not Aphanizomenon, showed in vitro evidence of immunosuppression—specifically inactivation of lymphocytes.8 A recent study from McGill University looked at the effects of Aphanizomenon on natural killer cell activity in 21 healthy volunteers and showed that there was an increase in migration of these cells into tissue, suggesting an immunostimulating effect.9 Still other species, distinct from those that are marketed, were found to have compounds with antiviral and antifungal properties.10,11
Marketers of Super Blue Green Algae, a product that contains Aphanizomenon flos-aquae, claim cholesterol reductions of as much as 75%. Reference is made to an animal study from Massachusetts General Hospital, which turns out to be a rat study showing that a diet supplemented with Aphanizomenon flos-aquae was more effective in lowering triglycerides and total cholesterol than a diet supplemented with soybean oil.12
Clinical Studies
Of the two human studies, both available in abstract only, one was performed in Japan looking at the effect of spirulina on cholesterol levels. Thirty hypercholesterolemic men were divided in two groups.13 The first group was given 4.2 g/d spirulina for eight weeks; at four weeks, average total serum cholesterol in this group dropped from 244 mg/dL to 233 mg/dL (4.5%). The second group received spirulina in the same dose for four weeks, then stopped. They had a similar decrease in total cholesterol, with a return to baseline at the end of eight weeks. The diet is described as being unchanged throughout the study.
The second study was performed in India. Spirulina fusiformis was studied for its ability to prevent premalignant lesions in tobacco chewers.14 Spirulina was given in a dose of 1 g/d for 12 months. Regression of oral leukoplakia was seen in 20 of 44 patients ingesting spirulina (45%) compared to three of 43 in the placebo group (7%). Within one year of discontinuing spirulina supplementation, recurrent lesions were seen in half of the initial responders.
Adverse Effects
Some cyanobacteria are capable of producing microcystins, which have a number of adverse health effects, including the promotion of hepatocellular carcinoma. Deaths in animals due to "algal blooms" have been recognized for decades, but it is only recently that human toxicity has been noted. A number of outbreaks related to contaminated sources of potable water have been identified.
The most lethal contamination evidenced microcystin poisoning and contamination of a hemodialysis system in Brazil. All 126 patients in the dialysis unit, which drew water from a fresh-water lake, developed acute neurotoxicity and hepatitis ranging from mild transaminase elevation to fulminant hepatic failure, ultimately resulting in the death of 60 patients.15
A second contamination was documented by the Oregon Health Division, which found that Aphanizomenon flos-aquae, harvested from Upper Klamath Lake, was frequently contaminated by Microcystis aeruginosa, an active producer of microcystins. In 1996, 63% of blue-green algae products tested by the Oregon Department of Agriculture had greater than the established limit of microcystins.16
There is some evidence that milder, microcystin-related symptoms of nausea, vomiting, and paresthesia occur more frequently than mass contamination. Sales representatives may indeed tell consumers that this is part of the "detoxification" process.17
Cyanobacteria can act as a reservoir for cholera.18 Contamination with heavy metals and radioactive ions have also been reported.
One Mexican study found that spirulina demonstrated no teratogenicity in rats fed varying amounts.19
Drug Interactions
There have not been any drug interactions with spirulina described in the literature. Theoretically, the phenylalanine content can exacerbate phenylketonuria.
Formulation
Marketers recommend doses in the 3-5 g/d range, generally taken before meals, as a tablet or as a powder mixed with juice. Unpleasant taste—often described as foul, seaweed-like, and unpalatable—is a limiting factor in the amount consumed.
Conclusion
Preliminary data suggest that cyanobacteria, including both commonly marketed Spirulina species and Aphanizomenon flos-aquae, contain compounds that may have beneficial health effects. It also is clear, however, that in vitro evidence from other Cyanobacteria species has been "extrapolated" to the marketed species.
Overall, evidence of beneficial effects in humans is lacking; what little there is falls well short of supporting the claims of the algae marketers. In addition, although blue-green algae certainly are rich in protein, there is nothing about the protein content that is superior to that found in meat, soy, beans, or dairy, and the cost is significantly greater. There also is some doubt as to spirulina’s ability to provide vitamin B12 that is bioavailable. Finally, non-Spirulina species present a significant health hazard of contamination by potentially neurotoxic microcystins.
Recommendation
Blue-green algae currently are not recommended for any indication. The evidence suggests awaiting further research concerning the antiviral, antineoplastic, and anti-inflammatory properties of blue-green algae. As a nutritional supplement, these products are very expensive; there are much more cost-effective ways to get the same nutrients. For those who still want to try blue-green algae, spirulina products appear to be safer than non-spirulina products (e.g., Aphanizomenon flos-aquae or "super blue-green algae"), which are grown in natural settings and potentially are contaminated with microcystins. Non- spirulina products are not recommended and should be discouraged.
Dr. Nardino is Program Director, Internal Medicine Residency, Hospital of San Raphael, New Haven, CT, and Assistant Clinical Professor of Medicine, Yale University School of Medicine.
References
1. Dagnelie PC, et al. Vitamin B-12 from algae appears not to be bioavailable [published erratum appears in Am J Clin Nutr 1991;53:988]. Am J Clin Nutr 1991;53: 695-697.
2. Watanabe F, et al. Pseudovitamin B(12) is the predominant cobamide of an algal health food, spirulina tablets. J Agric Food Chem 1999;47:4736-4741.
3. Schaeffer DJ, Krylov VS. Anti-HIV activity of extracts and compounds from algae and cyanobacteria. Ecotoxicol Environ Saf 2000;45:208-227.
4. Loya S, et al. Polycitone A, a novel and potent general inhibitor of retroviral reverse transcriptases and cellular DNA polymerases. Biochem J 1999;344(Pt 1):85-92.
5. Ayehunie S, et al. Inhibition of HIV-1 replication by an aqueous extract of Spirulina platensis (Arthrospira platensis). J Acquir Immune Defic Syndr Hum Retrovirol 1998;18:7-12.
6. Romay C, et al. Antioxidant and anti-inflammatory properties of C-phycocyanin from blue-green algae. Inflamm Res 1998;47:36-41.
7. Smith CD, et al. Reversal of multiple drug resistance by tolyporphin, a novel cyanobacterial natural product. Oncol Res 1994;6:211-218.
8. Effmert U, et al. Investigations of the immunomodulatory effect of cyanobacterial extracts [in German]. Allerg Immunol 1991;37:97-102.
9. Jensen G, et al. Consumption of Aphanizomenon flos-aquae has rapid effects on the circulation and function of immune cells in humans. JANA 2000;2:50-56.
10. Stewart JB, et al. Cytotoxic, fungicidal nucleosides from blue green algae belonging to the Scytonemataceae. J Antibiot (Tokyo) 1988;41:1048-1056.
11. Knubel G, et al. Cytotoxic, antiviral indolocarbazoles from a blue-green alga belonging to the Nostocaceae. J Antibiot (Tokyo) 1990;43:1236-1239.
12. Kushak RI, et al. Favorable effects of blue-green algae Aphanizomenon flos-aquae on rat plasma lipids. JANA 2000;2:59-65.
13. Nayaka N, et al. Cholesterol lowering effect of spirulina. Nutr Rep Int 1988;37:1329-1337.
14. Mathew B, et al. Evaluation of chemoprevention of oral cancer with Spirulina fusiformis. Nutr Cancer 1995;24:197-202.
15. Pouria S, et al. Fatal microcystin intoxication in haemodialysis unit in Caruaru, Brazil. Lancet 1998; 352:21-26.
16. Gilroy DJ, et al. Assessing potential health risks from microcystin toxins in blue-green algae dietary supplements. Environ Health Perspect 2000;108:435-439.
17. National Council Against Health Fraud. Growing concerns over blue-green algae. NCAHF News 1996;19:Issue 2. Available at: www.ncahf.org/nl/1996/3-4.html. Accessed February 7, 2001.
18. Islam MS, et al. Association of Vibrio cholerae O1 with the Cyanobacterium, Anabaena sp., elucidated by polymerase chain reaction and transmission electron microscopy. Trans R Soc Trop Med Hyg 1999;93:36-40.
19. Chamorro GA, et al. Short-term toxicity study of Spirulina in F3b generation rats. J Toxicol Clin Exp 1988;8:163-167.
June 2001; Volume 4; 67-70
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