Spirulina
Arthrospira platensis and Arthrospira maxima . Family: Phormidiaceae
Spirulina , dihe , tecuitlatl
 
Clinical Overview
Uses
Spirulina is sold in the United States as a health food or supplement. Diverse claims exist for its immunostimulatory, hypolipidemic, antiviral, and anticancer effects; however, there is limited evidence to support these indications.

Dosing
There is insufficient clinical data to guide dosing of spirulina for therapeutic effect.

Contraindications
Phenylketonuria; however, this has not been substantiated.

Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Because of possible mercury and other heavy metal contamination, spirulina should be avoided during pregnancy.

Interactions
None well documented.

Adverse Reactions
Few reports of adverse reactions are available. However, spirulina-associated hepatotoxicity and reactions from heavy metal contamination are possible.

Toxicology
Spirulina is considered nontoxic to humans at usual levels of consumption; however, information is limited.

 
Biology
Spirulina, a type of blue-green algae (cyanophytes/cyanobacteria), takes the form of microscopic, corkscrew-shaped filaments and is now classified as a distinct genus, with A. plantensis found in Africa and Asia and A. maxima found in Central America. 1 Free growing, spirulina lives in high-salt alkaline water in subtropical and tropical areas, sometimes imparting a dark-green color to bodies of water. 2 Spirulina is noted for its characteristic behavior in carbonated water and energetic growth in laboratory cultures. 3 It is commercially grown in the United States and has been proposed as the primary foodstuff to be cultivated during long-term space missions because it withstands extreme conditions. 4 , 5
 
History
Spirulina has been described in literature since the 16th century. Spanish explorers observed the Aztecs harvesting a blue mud that probably consisted of spirulina. The mud, which was dried to form chips or cheese-flavored loaves, was obtained from Lake Texcoco in Mexico. Spirulina was similarly harvested in the Sahara Desert where it was called dihe. Thus, two cultures approximately 10,000 km apart, independently discovered and utilized the nutritional properties of spirulina. 6
 
Chemistry
Spirulina consists of approximately 65% crude protein, high levels of B-complex vitamins, 7 vitamin E, 8 beta-carotene, and zeaxanthin. 3 , 9 The protein content includes 22 essential amino acids. 6 , 10 The protein C-phycocyanin found in spirulina has been the focus of much research. High levels of gamma linolenic acid, a polyunsaturated fatty acid, are present. 11 Spirulina preparations contain iron 300 to 400 ppm (dry weight). Unlike many forms of plant iron, this iron has high bioavailability when ingested by humans. A dosage of 10 g/day can contain 1.5 to 2 mg of absorbable iron, similar to standard ferrous sulfate. 12 , 13 Trace elements present at high levels include manganese, selenium, and zinc. Calcium, potassium, and magnesium are also concentrated in the organism. 14
 
Uses and Pharmacology
Clinical trials have investigated spirulina's potential but have failed to indicate any consistent effects.
Allergic rhinitis and asthma   Despite experimental data suggesting that C-phycocyanin can selectively inhibit release of histamine from mast cells and prevent increases in immunoglobulin E, studies demonstrating clinical efficacy are inadequate. A small study in patients with mild to moderate asthma suggested that spirulina supplementation (1 g/day) produced improvement in lung function parameters, 15 while a study evaluating spirulina in allergic rhinitis suggested a positive effect on laboratory values but no clinical outcomes were reported. 16
Antimicrobial activity   Spirulina and its extracts have been evaluated for antiviral activity. One in vitro study found that calcium spirulan extract interfered with replication of several enveloped viruses, including herpes simplex, cytomegalovirus, mumps and measles viruses, influenza A virus, and HIV-1, 17 while another study described a slightly different range of viruses susceptible to the extract. 18 HIV-1 adsorption and penetration were inhibited by an aqueous extract of spirulina, while a crude hot water extract reduced HIV-1 replication. 19 This type of in vitro activity is common to acidic polysaccharides from a variety of sources. Enterovirus is also susceptible to spirulina. 20 Spirulina demonstrated some in vitro activity against common human bacterial pathogens, but less than the standard comparator. 21
Cancer   C-phycocyanin showed a dose-dependent inhibition of HeLa and human chronic myeloid leukemia cell growth and proliferation in in vitro experiments. 22 , 23 Induction of apoptosis was considered to be one of the mechanisms involved. Survival rates increased in mice with liver cancer treated with C-phycocyanin, 24 and tumor regression has been reported in animals with oral cancer. 25 , 26 , 27 Spirulina induced lesion regression in tobacco chewers with oral leukoplakia in a study conducted in India. 28
Diabetes   Two small studies have investigated the effects of spirulina supplementation in type 2 diabetes, with improvement noted in fasting blood sugar and lipid profiles. Suggested mechanisms of action include hypoglycemia caused by fiber content or possible insulin-stimulating action of peptides and polypeptides of spirulina proteins. The actions on lipids have been attributed to gamma linolenic acid content. 29 , 30
Dietary supplement   Spirulina, considered a food item for centuries in many countries, is now popularly thought of as a dietary supplement. 4 Spirulina consumption was purported to aid in weight loss because of its high phenylalanine content, but a Food and Drug Administration review found no evidence to support this claim. 31 , 32 Suggestions that spirulina is a valuable source of vitamin B12 have been similarly disputed. 4
A study of spirulina supplementation for 8 weeks demonstrated clinical improvement in weight gain and increased hemoglobin levels in malnourished children in the West African nation of Burkina Faso. 33 Similar results have been demonstrated among children who are HIV-positive. 34
Hyperlipidemia   Experiments in rats suggest that C-phycocyanin exhibits hypercholesterolemic action. 35 Two small clinical studies have examined the role of spirulina in hyperlipidemia secondary to nephrotic syndrome. Both populations showed an improved lipid profile with spirulina supplementation; however, the control group in 1 experiment also showed improvement. The gamma linolenic acid content of spirulina may have played a role in the mechanism of action. 36 , 37
Immune system effects   In vitro and animal experiments suggest that spirulina and its extracts might be immunostimulatory. Activation of monocytes and macrophages, as well as 38 , 39 augmentation of interleukin and interferon production, have also been demonstrated. 40 A clinical study in healthy men found that oral administration of spirulina for 3 months resulted in enhanced interferon production and natural killer cell capacity. 19 The clinical importance of these effects has not been determined.
Other uses   In a small, randomized, placebo-controlled trial, spirulina plus zinc increased urinary excretion of arsenic and decreased arsenic hair-content in people with chronic exposure to arsenic. 41
C-phycocyanin inhibited platelet aggregation in in vitro experiments. 42 In mice with chemically-induced arthritis, phycocyanin exerted a scavenging action against reactive oxygen species and anti-inflammatory activity. 43
A 5% spirulina-supplemented diet prevented fatty liver in rats. 44 Spirulina decreased cisplatin-induced nephrotoxicity in rats, an effect attributed to an antioxidant action. 45 Other studies suggest that spirulina is an antioxidant, but clinical importance has not been demonstrated. Spirulina also has been reported to reduce gastric secretory activity 46 and protect mouse and human bone marrow cells against gamma radiation. 16 , 45 , 47 , 48 , 49 , 50
 
Administration & Dosage
There is insufficient clinical data to guide dosing of spirulina for therapeutic effect. Spirulina has typically been studied in daily dosage of 1 to 10 g. 15 , 33
 
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Spirulina may contain more than 180 mcg of mercury per 20 g of spirulina 14 and should be avoided.
 
Interactions
None well documented. An antiplatelet effect has been demonstrated in vitro but was not clinically evaluated. 42
 
Adverse Reactions
Few reports of adverse reactions are available. Cyanobacteria (blue-green algae) may contain the amino acid phenylalanine; therefore, people with phenylketonuria should avoid spirulina. 4 A case of spirulina-associated hepatotoxicity has been reported. 51 Hepatotoxic microcystins and neurotoxic anatoxin-a are produced by a number of cyanobacteria and have been reported as spirulina contaminants. 52 Other contaminants reported include the heavy metals mercury, cadmium, arsenic, and lead, as well as microbes cultivated on fermented animal waste. 14 , 53 Questions have been raised regarding the potential for adverse reactions in persons with autoimmune disorders consuming immunostimulatory herbal preparations. 54
 
Toxicology
Spirulina is considered nontoxic to humans at usual levels of consumption; however, information is limited.
 
References
 

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4. Robb-Nicholson C . By the way, doctor. I read that spirulina is the next wonder vitamin. What can you tell me about it? Harv Womens Health Watch . 2006;14(3):8.

 

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22. Subhashini J , Mahipal SV , Reddy MC , Mallikarjuna Reddy M , Rachamallu A , Reddanna P . Molecular mechanisms in C-Phycocyanin induced apoptosis in human chronic myeloid leukemia cell line-K562 . Biochem Pharmacol . 2004;68(3):453-462.  PubMed

 

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24. Li B , Zhang X , Gao M , Chu X . Effects of CD59 on antitumoral activities of phycocyanin from Spirulina platensis . Biomed Pharmacother . 2005;59(10):551-560.  PubMed

 

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27. Shklar G , Schwartz J . Tumor necrosis factor in experimental cancer regression with alphatocopherol, beta-carotene, canthaxanthin and algae extract . Eur J Cancer Clin Oncol . 1988;24(5):839-850.

 

28. Mathew B , Sankaranarayanan R , Nair PP , et al. Evaluation of chemoprevention of oral cancer with Spirulina fusiformis . Nutr Cancer . 1995;24(2):197-202.  PubMed

 

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30. Parikh P , Mani U , Iyer U . Role of spirulina in the control of glycemia and lipidemia in type 2 diabetes mellitus . J Med Food . 2001;4(4):193-199.  PubMed

 

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34. Simpore J , Zongo F , Kabore F , et al. Nutrition rehabilitation of HIV-infected and HIV-negative undernourished children utilizing spirulina . Ann Nutr Metab . 2005;49(6):373-380.  PubMed

 

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37. Samuels R , Mani UV , Iyer UM , Nayak US . Hypocholesterolemic effect of spirulina in patients with hyperlipidemic nephrotic syndrome . J Med Food . 2002;5(2):91-96.  PubMed

 

38. Pugh N , Ross SA , ElSohly HN , ElSohly MA , Pasco DS . Isolation of three high molecular weight polysaccharide preparations with potent immunostimulatory activity from Spirulina platensis, Aphanizomen flos-aquae and Chlorella pyrenoidosa . Planta Med . 2001;67(8):737-742.  PubMed

 

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40. Mao TK , Van de Water J , Gershwin ME . Effect of spirulina on the secretion of cytokines from peripheral blood mononuclear cells . J Med Food . 2000;3(3):135-140.  PubMed

 

41. Misbahuddin M , Islam AZ , Khandker S , Ifthaker-Al-Mahmud , Islam N , Anjumanara . Efficacy of spirulina extract plus zinc in patients of chronic arsenic poisoning: a randomized placebo-controlled study . Clin Toxicol (Phila) . 2006;44(2):135-141.  PubMed

 

42. Hsiao G , Chou PH , Shen MY , Chou DS , Lin CH , Sheu JR . C-phycocyanin, a very potent and novel platelet aggregation inhibitor from Spirulina platensis . J Agric Food Chem . 2005;53(20):7734-7740.  PubMed

 

43. Remirez D , González R , Merino N , Rodriguez S , Ancheta O . Inhibitory effects of Spirulina in zymosan-induced arthritis in mice . Mediators Inflamm . 2002;11(2):75-79.

 

44. Torres-Durán PV , Miranda-Zamora R , Paredes-Carbajal MC , Mascher D , Díaz-Zagoya JC , Juárez-Oropeza MA . Spirulina maxima prevents induction of fatty liver by carbon tetrachloride in the rat . Biochem Mol Biol Int . 1998;44(4):787-793.  PubMed

 

45. Mohan IK , Khan M , Shobha JC , et al. Protection against cisplatin-induced nephrotoxicity by Spirulina in rats . Cancer Chemother Pharmacol . 2006;58(6):802-808.  PubMed

 

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50. Klingler W , Kreja L , Nothdurft W , Selig C . Influence of different radioprotective compounds on radiotolerance and cell cycle distribution of human progenitor cells of granulocytopoiesis in vitro . Br J Haematol . 2002;119(1):244-254.  PubMed

 

51. Iwasa M , Yamamoto M , Tanaka Y , Kaito M , Adachi Y . Spirulina-associated hepatotoxicity . Am J Gastroenterol . 2002;97(12):3212-3213.  PubMed

 

52. Rawn DF , Niedzwiadek B , Lau BP , Saker M . Anatoxin-a and its metabolites in blue-green algae food supplements from Canada and Portugal . J Food Prot . 2007;70(3):776-779.  PubMed

 

53. Wu JF , Pond WG . Amino acid composition and microbial contamination of Spirulina maxima , a blue-green alga, grown on the effluent of fermented animal wastes . Bull Environ Contam Toxicol . 1981;27(2):151-159.  PubMed

 

54. Lee AN , Werth VP . Activation of autoimmunity following use of immunostimulatory herbal supplements . Arch Dermatol . 2004;140(6):723-727.  PubMed