Spirulina

Generic name: Arthrospira (Spirulina) Fusiformis, Arthrospira (Spirulina) Maxima Setchell Et Gardner, Arthrospira (Spirulina) Platensis (Nordstedt) Gomont
Brand names: Dihe, Spirulina, Tecuitlatl

Usage of Spirulina

Clinical trials have investigated spirulina's potential clinical applications but have been too small to support its purported effects.Karkos 2011

Allergic rhinitis and asthma

In vitro data

In vitro data have suggested that C-phycocyanin exhibits anti-inflammatory properties, selectively inhibiting release of histamine from rat mast cells and preventing increases in immunoglobulin E.Remirez 2002

Clinical data

A small study in patients with mild to moderate asthma (N=34) suggested that spirulina supplementation (1 g/day) produced improvement in lung function parameters.Labhe 2001 A study evaluating spirulina in patients with allergic rhinitis (N=36) suggested a positive effect on laboratory values, but no clinical outcomes were reported.Mao 2005 In a 6-month, double-blind, placebo-controlled study of patients with allergic rhinitis (N=150), spirulina 2 g/day was superior to placebo with regard to diary-based symptom scores of nasal discharge.Cingi 2008

Antibacterial/Antifungal activity

Animal and in vitro data

In vitro, spirulina demonstrated some activity against common human bacterial pathogens but less than that of the standard comparator.Ozdemir 2004 Immune stimulation by phycocyanin and polysaccharides of spirulina led to antifungal and antibacterial effects in mice.El-Sheekh 2010

Antioxidant effects

Animal and in vitro data

In vitro, the antioxidant activity of selenium-containing phycocyanin was evaluated using 4 different free-radical scavenging assays; results indicated that selenium-containing phycocyanin exhibits stronger antioxidant activity than phycocyanin.Chen 2008 In cellular assays of antioxidant activity, 4 commercial spirulina preparations were active.Dartsch 2008 Another in vitro study determined that both the phycocyanin and nonphycocyanin bioactive compounds in a novel A. platensis–based aqueous cyanophyta extract contributed to antioxidant and anti-inflammatory effects without a negative impact on blood clotting. In the presence of phycocyanin, nonphycocyanin, and aqueous cyanophyta extract, time for clot formation and lysis was not affected; however, clots were significantly more robust, with the effect statistically significant (P<0.05) at doses between 125 and 500 mcg/mL. Lipoxygenase inhibition was associated specifically with the nonphycocyanin components.Jensen 2015 In one study, spirulina supplementation in rats did not increase plasma or liver alpha-tocopherol levelsGarcía-Martínez 2007; however, another study in rats reported effective antioxidant activity using combinations of whey protein and spirulina.Gad 2011 In another study, C-phycocyanin from spirulina reduced oxidative stress in hamsters fed an atherogenic diet.Riss 2007 Similarly, in rabbits fed a 4-week high-cholesterol diet to induce hypercholesterolemia, an additional 8 weeks of spirulina 1% or 5% added to feed protected against oxidative stress.Kim 2010 In mice with zymosan-induced arthritis, phycocyanin exerted a scavenging action against reactive oxygen species, and also demonstrated anti-inflammatory activity in various in vitro and in vivo models.Remirez 2002 Pretreatment with spirulina 180 mg/kg orally in a rat cerebral ischemia-reperfusion injury model reduced neurologic deficits and histological changes.Thaakur 2010 A systematic review of preclinical in vivo and in vitro studies evaluating effects of spirulina (Arthrospira) and its extracts against specific toxicity induced by environmental and occupational pollutants showed strong antioxidant effects of spirulina, particularly of the C-phycocyanin protein, which has been shown to exhibit up to 20 times more antioxidant activity than ascorbic acid.Martinez-Galero 2016

Clinical data

Limited clinical studies suggest antioxidant effects of spirulina, but clinical importance has not been demonstrated.Deng 2010, McCarty 2007, Szulinska 2017 In one small clinical study, spirulina showed no effect on plasma antioxidant status.Shyam 2007

Antiplatelet/Anticoagulant activity

Ex vivo data

C-phycocyanin inhibited platelet aggregation in ex vivo experiments.Hsiao 2005

Clinical data

A small, double-blind, randomized, placebo-controlled trial (N=24) assessed the impact of aqueous cyanophyta extract from spirulina (2.3 g/day, equivalent to approximately 1 g/day of phycocyanin) on coagulation and platelet activation in adults with chronic pain. After 2 weeks, no significant difference was observed in platelet aggregation, platelet P-selectin expression, serum levels of soluble P-selectin, activated partial thromboplastin time, thrombin clotting time, or fibrinogen activity between the aqueous cyanophyta extract and placebo groups. Significant improvement in primary pain scores at rest and when active was noted in the aqueous cyanophyta extract group (P<0.01) and between groups (P<0.05). The liver enzyme AST was also significantly reduced in the aqueous cyanophyta extract group (P<0.001). Inhibition of cyclooxygenase 2 and activation of Nrf2 by phycocyanin have been identified as likely mechanisms of action.Jensen 2016

Antiviral activity

It has been suggested that cultures in which large amounts of algae are consumed have lower levels of HIV infection.Teas 2004 Spirulina and its extracts have been evaluated for antiviral activity.

In vitro data

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.Hayashi 1996 Another study described a slightly different range of viruses susceptible to the extract.Hernández-Corona 2002 HIV-1 adsorption and penetration were inhibited by an aqueous extract of spirulina, and a crude hot water extract reduced HIV-1 replication.Teas 2004 This type of in vitro activity is common to acidic polysaccharides from a variety of sources. Enterovirus is also susceptible to spirulina, with allophycocyanin being the active constituent.Shih 2003

Clinical data

An evidence-based review (14 studies including 1,725 adults and 271 children) evaluated the effects of nutritional supplements, including spirulina, in HIV-infected individuals. The reviewers stated that firm conclusions could not be drawn because of the small sample sizes and heterogeneity among studies. Risk of mortality was not significantly altered with nutritional supplementary food or supplemental spirulina compared with control (placebo or no supplement) in malnourished, antiretroviral therapy–naive adults in the 2 studies evaluating this outcome. In an 8-week pediatric study evaluating effects of spirulina 10 g/day (in addition to traditional meals) on anthropometric measures, no benefit was observed compared with control (traditional meal only group). In general, the available evidence did not support the use of specific macronutrients, whey protein, or spirulina to improve anthropometric, immunologic, or clinical outcomes in HIV-infected adults and children.Grobler 2013 In a 6-month, double-blind, randomized, comparative pilot trial conducted in 66 interferon-naive adults with unresponsive chronic hepatitis C, no difference in virological response was observed between spirulina (1,500 mg/day) and silymarin (420 mg/day) groups. However, supplementation with spirulina resulted in statistically significant improvements in serum ALT values (P=0.006), sexual function total scores (P=0.001), and overall quality-of-life scores (P=0.003). Mild, transient adverse events of nausea, bloating, giddiness, and headache were reported in fewer than 6 patients in both groups.Yakoot 2012

Arthritis

Animal and in vitro data

In mice with zymosan-induced arthritis, phycocyanin exerted a scavenging action against reactive oxygen species, and also demonstrated anti-inflammatory activity in various in vitro and in vivo models.Remirez 2002 In similar experiments of mice with complete Freund adjuvant–induced arthritis, spirulina 800 mg/kg orally for 8 days was effective in reducing inflammation.Rasool 2006 In rats, collagen-induced arthritis was inhibited by spirulina 400 mg/kg given for 45 days.Kumar 2009

Cancer

Animal and in vitro data

C-phycocyanin showed a dose-dependent inhibition of HeLa and human chronic myeloid leukemia cell growth and proliferation in vitro.Li 2006, Subhashini 2004 Induction of apoptosis was considered to be one of the mechanisms involved.Li 2005 A polysaccharide extract of spirulina was antiangiogenic in a mouse corneal model.Yang 2009 Doxorubicin-resistant HepG2 liver cancer cells were inhibited by spirulina C-phycocyanin through an apoptotic mechanism,Roy 2007 while water-soluble polysaccharides were implicated as the active agent against stomach cancer cells.Oh 2011 Survival rates increased in mice with liver cancer treated with C-phycocyanin, and tumor regression has been reported in animals with oral cancer.Schwartz 1987, Schwartz 1988, Shklar 1988 Activation of antitumor natural killer (NK) 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.Akao 2009 In a hamster cheek pouch model of carcinogenesis, 10 mg/day of spirulina extract reduced dysplastic changesGrawish 2008; these results were further confirmed by an immunohistochemical study.Grawish 2010 In rats, spirulina demonstrated a chemopreventive effect in dibutyl nitrosamine–induced carcinogenesis.Ismail 2009

Clinical data

In a study conducted in India, spirulina induced lesion regression in tobacco chewers with oral leukoplakia.Mathew 1995

Chelating effects

Animal and in vitro data

A protein extract and purified phycocyanin protected neuroblastoma cells from iron-induced toxicity.Bermejo-Bescós 2008 Diet supplemented with spirulina 5% prevented carbon tetrachloride–induced fatty liver in rats.Torres-Durán 1998 Cadmium toxicity in rats was reduced by spirulina, as measured by liver histopathology.Karadeniz 2009 Mercuric chloride–induced oxidative stress in mice was blocked by spirulina 800 mg/kg orally for 40 days.Sharma 2007 Lead acetate damage to rats was minimized by spirulina via normalizing plasma and liver lipid levels, as well as via antioxidant effects.Ponce-Canchihuamán 2010 S. platensis pretreatment protected mice against acetaminophen- and galactosamine-induced hepatitis.Lu 2010 Liver and kidney enzyme markers of toxicity were reduced with spirulina administration following 4-nitroquinoline 1-oxide insult to rats.Viswanadha 2011 Spirulina decreased cisplatin-induced nephrotoxicity in rats, an effect attributed to its antioxidant action.Mohan 2006 Gentamicin-induced kidney damage in rats was reversed by intraperitoneal administration of spirulina 1 g/kg daily.Karadeniz 2008 In a study of pregnant mice, intragastric administration of spirulina 125 to 500 mg/kg for 17 days of gestation reduced teratogenicity due to cadmium.Paniagua-Castro 2011 In mice injected with cyclophosphamide, pretreatment with spirulina reduced mutagenicity of cyclophosphamide.Chamorro-Cevallos 2008 A systematic review of preclinical in vivo and in vitro studies of the antitoxic properties of Spirulina spp. to environmental pollutants supports the strong antioxidant effects of spirulina and notes very few reports of adverse events.Martinez-Galero 2016

Clinical data

In a small, randomized, placebo-controlled trial, spirulina plus zinc increased urinary excretion of arsenic and decreased arsenic hair content in individuals with long-term exposure to arsenic.Misbahuddin 2006

Diabetes/Metabolic syndrome

Animal data

In a study of rats with alloxan-induced diabetes, spirulina 10 mg/kg orally for 30 days lowered glucose levels while slightly elevating insulin.Muthuraman 2009

Clinical data

Two small clinical studies (N=15 and N=25) investigated the effects of spirulina supplementation in type 2 diabetes; improvement was 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.Mani 2000, Parikh 2001 More recent systematic reviews of interventional trials exploring the effects of spirulina on metabolic syndrome have been conducted. In a randomized, controlled, double-blind trial (N=50), insulin sensitivity and low-density lipoprotein (LDL) cholesterol were reported to be significantly improved with administration of spirulina supplementation compared with placebo in obese patients with stable, treated hypertension (P<0.001).Szulinska 2017 Based on limited and/or equivocal data, spirulina is likely to improve glucose metabolism, lipid parameters, and possibly blood pressure for some patient populations with metabolic syndrome.van den Driessche 2018, Yousefi 2019

Dietary supplement

Spirulina, historically considered a food item in many countries, is now popularly thought of as a dietary supplement.Robb-Nicholson 2006 Spirulina has been purported to aid in weight loss because of its high phenylalanine content, but an FDA review found no evidence to support this claim.Saper 2004 Suggestions that spirulina is a valuable source of vitamin B12 have been similarly disputed.Robb-Nicholson 2006

Animal data

Skeletal muscle protein (myosin) was increased in young rats fed spirulina as the sole dietary protein source compared with those fed casein.Voltarelli 2008

Clinical data

In a study of malnourished children in the West African nation of Burkina Faso, spirulina supplementation for 8 weeks demonstrated clinical improvement in weight gain and increased hemoglobin levels.Simpore 2006 Similar nutritional rehabilitation results have been demonstrated among HIV-positive children receiving spirulina.Simpore 2005 Both motor and mental development scores were significantly improved in preschool children aged 6 to 18 months in Zambia 1.5 years after the completion of 16 months of spirulina supplementation compared to no supplementation. Data collected from 370 of the original 540 children enrolled in the initial open-label trial revealed significantly higher gross and fine motor skills (P<0.001) as well as language and personal-social skills (P<0.05). Greater improvements were observed in children with baseline values that were moderately to severely stunted and/or whose dietary diversity was below median.Masuda 2019 In a randomized, double-blind, placebo-controlled study of elderly Koreans, a variety of positive effects (cholesterol, antioxidant status, interleukin 2 [IL-2] and IL-6 levels) were observed with administration of spirulina 8 g/day for 16 weeks.Park 2008 In another double-blind, randomized, controlled trial involving 50 obese adults with medication-controlled hypertension and no concomitant conditions, supplementation with 2 g/day of S. maxima for 3 months did not result in beneficial changes in plasma mineral levels (ie, calcium, magnesium, zinc) but did lead to significantly lower iron levels compared with placebo (P=0.008).Suliburska 2016

Fatigue

Clinical data

Although spirulina supplementation (3 g/day) was ineffective against idiopathic chronic fatigue in one small study, it showed improvements in some physical and mental fatigue parameters in healthy, active men in another small study.Baicus 2007, Johnson 2016 In a small study of moderately trained males, spirulina increased time to fatigue, decreased carbohydrate oxidation rate, and increased fat oxidation rate, leading to an increase in exercise performance.Kalafati 2010

Hepatoprotective effects

Clinical data

In a case series of 3 patients with nonalcoholic fatty liver disease, spirulina 4.5 g/day for 3 months improved ALT values and lipid profiles.Ferreira-Hermosillo 2010

Hypertension

Clinical data

In a small pilot study of patients with systemic arterial hypertension (N=16; 3 men, 13 women) treated with angiotensin-converting enzyme (ACE) inhibitors, adjunctive oral supplementation with S. maxima 4.5 g/day for 12 weeks significantly improved mean systolic blood pressure compared with placebo (126 vs 140 mm Hg; P<0.05), as well as some but not all markers of endothelial damage and antioxidant status. Reported adverse events were similar between groups.Martínez-Sámano 2018 However, in a small, double-blind, randomized, placebo-controlled trial in 24 adults with chronic pain, no difference in systolic or diastolic blood pressure was observed between placebo patients and those receiving aqueous cyanophyta extract (2.3 g/day, equivalent to approximately 1 g/day of phycocyanin).Jensen 2016

Immune system effects

Animal and experimental data

Most in vitro and animal experiments have suggested immunostimulatory effects; however, one in vitro study found a spirulina extract to be immunosuppressive.Rasool 2009 Activation of monocytes and macrophages,Balachandran 2006, Pugh 2001 as well as augmentation of interleukin and interferon production, have been demonstrated.Mao 2000 In a study of aged mice, treatment with spirulina increased intestinal epithelial lymphocytes compared with the control aged group.Hayashi 2009 An ex vivo study of NK cells from spirulina-treated healthy patients showed increased NK activity, an effect confirmed by a second study in which NK cell and T-cell markers were increased with spirulina.Nielsen 2010

Clinical data

In a study in healthy men, oral administration of spirulina for 3 months resulted in enhanced interferon production and NK cell capacity.Teas 2004 A trial in elderly patients showed positive effects on anemia and immunosenescence after 6 and 12 weeks of spirulina supplementation.Selmi 2011 Immunostimulatory effects appear to be largely mediated by spirulina polysaccharides.Balachandran 2006, Pugh 2001 In a small, double-blind, randomized, placebo-controlled study of 19 trained male athletes, supplementation with spirulina 1,500 mg/day for 6 weeks appeared to mitigate exercise-induced reductions in some immune parameters, suggesting a potential preventative effect against strenuous exercise–induced immune deficits.Juszkiewicz 2018

Lipid effects

Animal data

Experiments in rats suggest that C-phycocyanin exhibits hypocholesterolemic action.Nagaoka 2005 In rabbits fed a high-cholesterol diet, the addition of spirulina (1% or 5%) lowered serum triglycerides, total cholesterol, and LDL at 8 weeks. High-density lipoprotein (HDL) was markedly increased.Cheong 2010

Clinical data

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 one experiment also showed improvement. The gamma linolenic acid content of spirulina may have played a role in the mechanism of action.Khanam 2001, Samuels 2002 A study in type 2 diabetes patients reported a reduction in triglycerides with use of spirulina 8 g/day for 12 weeks.Lee 2008 In studies of healthy volunteers, spirulina 4.5 g/day for 6 weeks lowered blood pressure, total cholesterol, and LDL, and increased HDL.Juárez-Oropeza 2009, Torres-Duran 2007 In a 15-day study of healthy runners, spirulina 5 g/day produced a significant reduction (−20%) in postprandial triglyceride levels compared with baseline (P=0.04). Subgroup analysis found that triglyceride reduction was greatest in 10- to 12-year-old study participants.Torres-Durán 2012 In a case series of 3 patients with nonalcoholic fatty liver disease, spirulina 4.5 g/day for 3 months improved ALT values and lipid profiles.Ferreira-Hermosillo 2010 A systematic review and meta-analysis identified 7 randomized controlled trials (N=522) evaluating spirulina's effects on lipid parameters. Diagnoses of participants included type 2 diabetes, ischemic heart disease, overweight, nephrotic syndrome, and HIV, with one trial enrolling volunteers. Pooled results supported efficacy of spirulina in improving total cholesterol (weighed mean difference [WMD], −46.76 mg/dL; P<0.001), LDL (WMD, −41.32 mg/dL; P<0.001), triglycerides (WMD, −44.23 mg/dL; P<0.001), and HDL (WMD, +6.06 mg/dL; P=0.001); effects were independent of dose. No adverse events were reported for any dosages used (1 to 10 g/day for durations of 2 to 12 months).Serban 2016 Recent systematic reviews of interventional trials exploring the effects of spirulina on metabolic syndrome suggest spirulina is likely to improve glucose metabolism and lipid parameters in some patient populations with metabolic syndrome, based on limited and/or equivocal data.van den Driessche 2018, Yousefi 2019

Neuroinflammation

Animal data

A rat study showed that spirulina potentially protects neural stem cells and promotes their growth.Bachstetter 2010

Clinical data

An amyotrophic lateral sclerosis (ALS) support network did not find evidence sufficiently compelling to support use of spirulina in ALS and states that better efficacy and safety studies are needed.ALSUntangled 2011

Obesity

Clinical data

Recent systematic reviews of interventional trials exploring the effects of spirulina on metabolic syndrome report a potential beneficial effect on weight reduction in populations with metabolic syndrome based on limited and/or equivocal data.van den Driessche 2018, Yousefi 2019 In a double-blind, randomized, placebo-controlled crossover trial in 52 obese or overweight sedentary Mexican men, spirulina alone and in combination with a physical exercise program reduced body weight compared with the placebo phase. Obese men experienced more benefit than their overweight counterparts. Cardiorespiratory fitness was similarly improved with spirulina with and without exercise, with more benefit evident in the obese group.Hernández-Lepe 2018

Osteoporosis

Animal data

In a study of rosiglitazone-treated rats, oral treatment with spirulina 500 mg/kg/day reduced the risk of osteoporosis.Gupta 2010

Radioprotective effects

In vitro data

Spirulina has been reported to protect mouse and human bone marrow cells against gamma radiation.Klingler 2002, Lu 2006, Mao 2005, Mohan 2006, Qishen 1989, Wu 2005

Spirulina side effects

Few reports of adverse reactions are available. Case reports of immunoblisteringKraigher 2008 and rhabdomyolysisMazokopakis 2008 linked to spirulina have been published. Cyanobacteria (blue-green algae) may contain the amino acid phenylalanine; therefore, individuals with phenylketonuria should avoid spirulina.Robb-Nicholson 2006 A case of spirulina-associated hepatotoxicity has been reported.Iwasa 2002 Hepatotoxic microcystins and neurotoxic anatoxin-a are produced by a number of cyanobacteria and have been reported as spirulina contaminants.Jiang 2008, Rawn 2007 Other contaminants include the heavy metals mercury, cadmium, arsenic, and lead, as well as microbes cultivated on fermented animal waste.Johnson 1986, Wu 1981 There may be a potential for adverse reactions in individuals with autoimmune disorders who consume immunostimulatory herbal preparations.Lee 2004 Two cases of anaphylaxis in young, atopic teenage boys have been reported, each occurring within 10 minutes to 6 hours of consuming spirulina tablets. In both cases, the reaction was confirmed as a positive allergic reaction to S. platensis via skin prick tests. In one case, the offending allergen was positively identified as C-phycocyanin protein.Le 2014, Petrus 2010 A case of Stevens-Johnson syndrome in a patient with Cushing disease was suspected to have developed 1 week after taking a spirulina product.Mustafa 2009

Before taking Spirulina

Information regarding safety and efficacy in pregnancy and lactation is lacking. Spirulina may contain more than 180 mcg of mercury per 20 gJohnson 1986 and should be avoided during pregnancy. A case of neonatal hypercalcemia, considered a likely result of maternal exposure to excessive S. platensis, was reported in a 1-day-old newborn. Subsequent to 5 months of daily maternal spirulina consumption, spirulina-related toxicity was suspected to have caused hydroxylation of 25-hydroxycholeCalciferol to Calcitriol, resulting in fetal hypercalcemia.Moulis 2012

How to use Spirulina

Clinical data are insufficient to guide therapeutic dosing of spirulina. Spirulina has typically been studied in daily dosages of 1 to 10 g, usually in divided doses, for durations of 15 days to 12 months.Grobler 2013, Labhe 2001, Serban 2016, Simpore 2006, Torres-Durán 2012, Yousefi 2019

Warnings

Information is limited. Spirulina is considered nontoxic to humans at usual levels of consumption and has GRAS status according to the FDA. Excessive spirulina consumption (daily for 5 months) during the last 2 trimesters of pregnancy was considered the likely cause of fetal hypercalcemia in a newborn.Moulis 2012

What other drugs will affect Spirulina

None well documented. An antiplatelet effect has been demonstrated in vitro but was not clinically evaluated.Hsiao 2005 A likely lab specimen interference was suspected in an otherwise healthy, asymptomatic 55-year-old female who presented for her annual physical with very high carbohydrate antigen levels; the patient had been taking spirulina health products for approximately 6 months. Interference was noted in 2 different assay methods (ARCHITEXT i2000 and cobas E601).Li 2015

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