Spirulina

Scientific Name(s): Arthrospira platensis (Nordstedt) Gomont and Arthrospira maxima Setchell et Gardner. Family: Phormidiaceae

Common Name(s): Spirulina , dihe , tecuitlatl

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

Doses in clinical studies have ranged from 1 to 10 g/day.

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.

Spirulina, a blue-green algae (cyanophytes/cyanobacteria), grows as microscopic, corkscrew-shaped multicellular filaments and is now classified as a distinct genus, Arthrospora . A. plantensis is found in Africa and Asia, and A. maxima is found in Central America. 1 , 2 Free growing, spirulina exists only in high-salt alkaline water in subtropical and tropical areas, sometimes imparting a dark-green color to bodies of water. 3 Spirulina is noted for its characteristic behavior in carbonated water and energetic growth in laboratory cultures. 4 It is commercially grown in the United States and has been proposed as a primary foodstuff to be cultivated during long-term space missions because it withstands extreme conditions. 5 , 6 Due to its unique growth requirements, contamination of open pond cultures of spirulina by other microorganisms is usually slight, with the alga growing as a relatively pure culture.

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. 2 The mud, which was dried to form chips or flavored loaves, was obtained from Lake Texcoco near Mexico City. Spirulina was similarly harvested in the Sahara Desert from small lakes near Lake Chad, where it was called dihe . Thus, 2 cultures approximately 10,000 km apart, independently discovered and utilized the nutritional properties of spirulina. 2 Currently, spirulina is actively marketed by numerous companies as a nutritional supplement. 7

Chemistry

Spirulina is composed of approximately 65% crude protein, high levels of B-complex vitamins, 8 vitamin E, 9 beta-carotene, 10 and zeaxanthin. 4 , 11 The protein content includes 22 essential amino acids, 2 , 12 and the total protein is nutritionally superior to legume protein, but inferior to meat protein. 2 The proteins C-phycocyanin and allophycocyanin in spirulina have been the focus of much research. 13 , 14 High levels of gamma linolenic acid, a polyunsaturated fatty acid, are present. 15 An assay for spirulina lipids using high-pressure liquid chromatography-mass spectrometry has been developed. 16 Spirulina preparations contain 300 to 400 ppm iron (dry weight), and unlike many forms of plant 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 that of standard ferrous sulfate. 17 , 18 Trace elements present at high levels include manganese, selenium, and zinc. Calcium, potassium, and magnesium are also concentrated in the organism. 19 Calcium spirulan, a sulfated polysaccharide, was characterized from A. platensis . 20

Uses and Pharmacology

Clinical trials have investigated spirulina's potential but have been too small to support its purported effects. 21

Allergic rhinitis and asthma

Experimental data have suggested that C-phycocyanin can selectively inhibit release of histamine from mast cells and prevent increases in immunoglobulin E. A small study in patients with mild to moderate asthma suggested that spirulina supplementation (1 g/day) produced improvement in lung function parameters, 22 while a study evaluating spirulina in allergic rhinitis suggested a positive effect on laboratory values, but no clinical outcomes were reported. 23 A 6-month, double-blind, placebo-controlled study enrolling 150 patients with allergic rhinitis found efficacy for 2 g/day of spirulina over placebo using diary-based symptom scores of nasal discharge. 24

Antimicrobial activity

A provocative suggestion has been made that human cultures in which large amounts of algae are consumed have lower levels of HIV infection. 25 Spirulina and its extracts have been evaluated for antiviral activity. One in vitro study found that the sulfated polysaccharide calcium spirulan interfered with the replication of several enveloped viruses, including herpes simplex, cytomegalovirus, mumps, measles, influenza A, and HIV-1, 20 while another study described a slightly different range of viruses susceptible to the extract. 26 HIV-1 adsorption and penetration were inhibited by an aqueous extract of spirulina, while a crude hot water extract reduced HIV-1 replication. 25 This type of in vitro activity is common to acidic polysaccharides from a variety of sources. Enterovirus is also susceptible to spirulina, and allophycocyanin was the active constituent. 27 Spirulina demonstrated some in vitro activity against common human bacterial pathogens but less than that of the standard comparator. 28 Immune stimulation by phycocyanin and polysaccharides of spirulina led to an antifungal and antibacterial effect in mice. 29

Cancer

C-phycocyanin showed a dose-dependent inhibition of HeLa and human chronic myeloid leukemia cell growth and proliferation in vitro. 30 , 31 Induction of apoptosis was considered to be one of the mechanisms involved. 32 Doxorubicin-resistant HepG2 liver cancer cells were inhibited by spirulina C-phycocyanin through an apoptotic mechanism, 33 while water-soluble polysaccharides were implicated as the active agent against stomach cancer cells. 34 A combination of selenium and spirulina inhibited MCF-7 breast cancer cells via growth arrest and apoptosis. 35 Survival rates increased in mice with liver cancer treated with C-phycocyanin, and tumor regression has been reported in animals with oral cancer. 36 , 37 , 38 Activation of antitumor natural killer cells by spirulina enhanced antitumor efficacy in a B16 mouse melanoma model, and the effect was abolished in MyD88 null/null mice, indicating that NK cell activation was a key pathway. 39 In a hamster cheek pouch model of carcinogenesis, 10 mg/day of spirulina extract reduced dysplastic changes, 40 which was further confirmed by an immunohistochemical study. 41 Spirulina was chemopreventative in a dibutyl nitrosamine carcinogenesis model. 42 It also induced lesion regression in tobacco chewers with oral leukoplakia in a study conducted in India. 43

Diabetes

A study in alloxan-induced diabetic rats revealed that spirulina at 10 mg/kg orally for 30 days lowered glucose levels, while slightly elevating insulin. 44 Two small clinical studies 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. 45 , 46

Dietary supplement

Spirulina, considered a food item for centuries in many countries, is now popularly thought of as a dietary supplement. 5 Spirulina consumption was purported to aid in weight loss because of its high phenylalanine content, but a US Food and Drug Administration review found no evidence to support this claim. 47 , 48 Suggestions that spirulina is a valuable source of vitamin B 12 have been similarly disputed. 5 Skeletal muscle protein (myosin) was increased in young rats fed spirulina as the sole dietary protein source compared with casein. 49 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. 50 Similar results have been demonstrated among children who are HIV-positive. 51 In elderly Koreans, spirulina 8 g/day for 16 weeks had a variety of positive effects (cholesterol, antioxidant status, interleukin [IL]-2 and IL-6 levels) observed in a randomized, double-blind, placebo-controlled study. 52 In a study of athletic training, spirulina increased time to fatigue, decreased carbohydrate oxidation rate, and increased fat oxidation rate, leading to an increase in exercise performance. 53

Hyperlipidemia

Experiments in rats suggest that C-phycocyanin exhibits hypercholesterolemic action. 54 In rabbits fed a high-cholesterol diet, spirulina (1% or 5% in diet) lowered serum triglycerides, total cholesterol, and low-density lipoprotein (LDL) at 8 weeks. High-density lipoprotein (HDL) was markedly increased. 55 Two small clinical studies 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. 56 , 57 A study in type 2 diabetes patients reported a reduction in triglycerides with 8 g/day of spirulina. 58 In normal volunteers, 4.5 g/day of spirulina for 6 weeks lowered blood pressure, total cholesterol, LDL, and increased HDL. 59 , 60

Immune system effects

Most in vitro and animal experiments have suggested immunostimulatory effects; however, 1 study found a spirulina extract to be immunosuppressive. 61 Activation of monocytes and macrophages, 62 , 63 as well as augmentation of interleukin and interferon production, have been demonstrated. 64 Intestinal epithelial lymphocytes of aged mice treated with spirulina were increased compared with the control aged group. 65 A clinical study in healthy men found that oral administration of spirulina for 3 months resulted in enhanced interferon production and natural killer (NK) cell capacity. 25 An ex vivo study of NK cells from spirulina-treated healthy patients showed increased NK activity, which was confirmed by a second study in which NK cell and T-cell markers were increased by spirulina. 66 A clinical trial in elderly patients showed positive effects on anemia and immunosenescence after 6 and 12 weeks of supplementation. 67 The immunostimulatory effects appear to be largely mediated by spirulina polysaccharides. 62 , 63

Prevention of toxicity due to metals or organic compounds

A 5% spirulina-supplemented diet prevented carbon tetrachloride-induced fatty liver in rats. 68 In a case series of 3 patients with nonalcoholic fatty liver disease, 4.5 g/day of spirulina for 3 months improved ALT values and lipid profiles. 69 Cadmium toxicity in rats was reduced by spirulina, as measured by liver histopathology. 70 Mercuric chloride-induced oxidative stress in mice was blocked by spirulina at 800 mg/kg orally for 40 days. 71 Lead acetate damage to rats was minimized by spirulina via normalizing plasma and liver lipid levels, as well as via its antioxidant effect. 72 A protein extract and purified phycocyanin protected neuroblastoma cells from iron-induced toxicity. 73 Spirulina pretreatment protected mice against acetaminophen and galactosamine-induced liver damage. 74 Liver and kidney enzyme markers of toxicity were reduced by spirulina following 4-nitroquinoline 1-oxide insult to rats. 75 Spirulina decreased cisplatin-induced nephrotoxicity in rats, an effect attributed to an antioxidant action. 76 Gentamicin-induced kidney damage in rats was reversed by intraperitoneal spirulina 1 g/kg daily. 77 In pregnant mice, teratogenicity due to cadmium was reduced by 125 to 500 mg/kg of spirulina by intragastric administration for 17 days of gestation. 78 Mutagenicity of cyclophosphamide in mice pretreated with spirulina was reduced. 79 In a small, randomized, placebo-controlled trial, spirulina plus zinc increased urinary excretion of arsenic and decreased arsenic hair-content in people with long-term exposure to arsenic. 80

Antioxidant

The spirulina protein phycocyanin in pure form was active in 4 different cell-free radical-scavenging assays; however, phycocyanin-containing selenium was more effective. 81 In cellular assays of antioxidant activity, 4 commercial spirulina preparations were also active. 82 Spirulina supplementation of rats did not increase plasma or liver alpha-tocopherol levels 83 ; however, another study reported effective antioxidant activity using combinations of whey protein and spirulina. 84 C-phycocyanin from spirulina reduced oxidative stress in hamsters fed an atherogenic diet. 85 Similarly, rabbits fed a high-cholesterol diet were protected from oxidative stress by 4 to 8 weeks of spirulina in feed at 1% or 5%. 86 Other studies suggest spirulina as an antioxidant, 87 but clinical importance has not been demonstrated, 88 , 89 and 1 small clinical study showed spirulina to be without effect on plasma antioxidant status. 90

Other uses

C-phycocyanin inhibited platelet aggregation in ex vivo experiments. 91 In mice with zymosan-induced arthritis, phycocyanin exerted a scavenging action against reactive oxygen species and anti-inflammatory activity. 92 Similar experiments with complete Freund's adjuvant-induced arthritis found 800 mg/kg of oral spirulina effective in reducing inflammation. 93 In rats, collagen-induced arthritis was inhibited by 400 mg/kg of spirulina. 94 Osteoporosis was inhibited in rosiglitazone-treated rats by 500 mg/kg/day of oral spirulina. 95 A rat study showed evidence that spirulina could protect neural stem cells and promote their growth 96 ; however, an amyotrophic lateral sclerosis (ALS) support network did not find the evidence compelling for use in ALS. 97 Spirulina supplementation (3 g/day) was ineffective against idiopathic chronic fatigue in a small study. 98 Pretreatment with spirulina 180 mg/kg orally in a rat cerebral ischemia-reperfusion injury model reduced neurologic deficits and histological changes. 99 A polysaccharide extract of spirulina was antiangiogenic in a mouse corneal model. 100 Spirulina also has been reported to protect mouse and human bone marrow cells against gamma radiation. 23 , 76 , 87 , 101 , 102 , 103

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. 22 , 50

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 19 and should be avoided.

Interactions

None well documented. An antiplatelet effect has been demonstrated in vitro but was not clinically evaluated. 91

Adverse Reactions

Few reports of adverse reactions are available. Case reports of immunoblistering 104 and rhabdomyolysis 105 linked to spirulina have been published. Cyanobacteria (blue-green algae) may contain the amino acid phenylalanine; therefore, people with phenylketonuria should avoid spirulina. 5 A case of spirulina-associated hepatotoxicity has been reported. 106 Hepatotoxic microcystins and neurotoxic anatoxin-a are produced by a number of cyanobacteria and have been reported as spirulina contaminants. 107 , 108 Other contaminants include the heavy metals mercury, cadmium, arsenic, and lead, as well as microbes cultivated on fermented animal waste. 19 , 109 Questions have been raised regarding the potential for adverse reactions in people with autoimmune disorders who consume immunostimulatory herbal preparations. 110

Toxicology

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

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