Quick Navigation

Spirulina

Spirulina is a non-toxic blue-green algae. It is a source of phycocyanobilin. Preliminary evidence suggests spirulina is remarkably potent at protecting the brain and reducing liver fat.

Our evidence-based analysis on spirulina features 205 unique references to scientific papers.

Research analysis led by Kamal Patel .
Reviewed by
Examine.com Team
Last Updated:

Summary of Spirulina

Primary Information, Benefits, Effects, and Important Facts

Spirulina is a blue-green algae. It is an easily produced, non-toxic species of Arthrospira bacteria.

Spirulina is often used as a vegan source of protein and vitamin B12. It is between 55-70% protein, but studies suggest it is a subpar source of B12, as the vitamin is not absorbed well after ingestion.

Human evidence suggests that spirulina can improve lipid and glucose metabolism, while also reducing liver fat and protecting the heart. Animal studies are very promising as well, as spirulina has been shown to be of similar potency as commonly used reference drugs, when it comes to neurological disorders. These effects also extend to arthritis and immunology.

Spirulina has a few active components. The main ingredient is called phycocyanobilin, which makes up about 1% of spirulina. This compound mimics the body’s bilirubin compound, in order to inhibit an enzyme complex called Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase. By inhibiting NADPH oxidase, spirulina provides potent anti-oxidative and anti-inflammatory effects.

The neurological effects of spirulina need more human evidence. Based on animal evidence, spirulina appears to be a promising anti-oxidant and supplement for metabolic issues.

Evidence-based information on what works

No fake reviews. No selling you supplements. Just the science.

Our free supplement mini-course teaches you what works, what's a waste, and how to achieve your health goals.

Join the over 200,000 people who have gone through this course (saving themselves time, money, and stress).

  • An allergic reaction to spirulina has been reported, although overall frequency of allergic responses or cross-sensitivities are not yet known

  • Preliminary evidence has suggested a reduction in the activities of the enzymes CYP2C6, CYP1A2, and CYP2E1

  • The same evidence has noted an upregulation (increase in activity) for both CYP2B1 and CYP3A1

How to Take Spirulina

Recommended dosage, active amounts, other details

The dose of spirulina used in studies examining its effects vary greatly. In general, 1-8 g per day of spirulina has been shown to have some effect. The specific doses depend on the condition its being used for:

  • For cholesterol, doses in the range of 1-8 g per day may be impactful

  • For muscle performance, doses of 2-7.5 g per day have been used

  • For blood glucose control, very mild effects have been seen with 2 g per day

  • Blood pressure may be affected at doses of 3.5-4.5 g per day

  • Effects for fatty liver have been seen at doses of 4.5 g per day

Spirulina is about 20% C-phycocyanin by weight, and about 1% phycocyanobilin by weight. The dosage range of 200mg/kg C-phycocyanin (1g/kg spirulina) in rats is approximately:

  • 10.9g for a 150lb person

  • 14.5g for a 200lb person

  • 18.2g for a 250lb person

Further research is needed to determine whether spirulina should be taken once a day, or in smaller doses, multiple times per day.

It is not recommended to exceed the highest dose mentioned above, as no clear benefits have been noted beyond that level.

Stop wasting time: achieve your health goals with our science-based recommendations

At Examine.com, we pride ourselves on basing all our recommendations on the evidence. It’s why we don’t sell any advertising or supplements — so that you know that our analysis is unbiased.

If you’re tired of wasting time and money on supplements that don’t work, our 17 Supplement Guides will help you figure out precisely what to take — and what to skip — based on your health goals and the latest scientific evidence.


I want science-based recommendations »

Frequently Asked Questions about Spirulina

4 science-based “superfoods” you should consider eating
"Superfood" is a pretty overrated phrase, but here are four foods that have evidence-backed benefits.

Get access to the latest nutrition research

By becoming an Examine.com Member, you'll have access to all of the latest nutrition research on over 300 supplements across over 500 different health goals, outcomes, conditions, and more.

Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects spirulina has on your body, and how strong these effects are.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-b Notable Very High See all 3 studies
Although there is no reference drug to compare the effects of Spirulina against, the decrease in lipid peroxidation as assessed by serum MDA is quite notable and is likely stronger than other supplements. A comparative study would be needed
grade-b Notable Moderate See all 8 studies
In populations with metabolic syndrome or related morbidities (diabetes, hyperlipidemia, hypertension, etc.) spirulina in a variety of doses between 1-8g daily is able to reduce triglycerides up to 10-15%.
grade-b Minor Very High See all 7 studies
A positive influence of spirulina on HDL-C appears to be present, but the magnitude of benefit is not overly remarkable and varies depending on the disease state (with states associated with fatty liver having a much greater increase in HDL-C seen with spirulina)
grade-b Minor Very High See all 6 studies
Degree of efficacy seems variable and correlated with disease state (more drastic improvements when LDL-C is much higher) but currently does not appear to be overly remarkable unless fatty liver exists.
grade-b Minor High See all 3 studies
Studies currently assessing the effects of spirulina on muscular endurance are too hetereogeneous to properly assess potency thereof. However, a positive effect does appear to exist
grade-b Minor Very High See all 6 studies
Reductions in cholesterol seen are positive, but not overly remarkable
grade-c Strong - See study
The lone study suggests that spirulina is strongly effective in controlling allergies, with the symptoms of nasal discharge, sneezing, nasal congestion and itching being time-dependently reduced. According to self-reports, more than twice as many subjects in the spirulina group reported more than a 2-fold increase in satisfaction with treatment.
grade-c Strong - See study
The decrease in nasal congestion seen in the one study was remarkably strong relative to placebo in a model of allergic rhinitus; it is not sure if this applies to other causes of nasal congestion.
grade-c Notable Moderate See all 3 studies
Insufficient evidence to fully evaluate the effects on blood pressure, but given how 6 weeks supplementation reduced both systolic and diastolic in nonhypertensive persons by about 11/6 points it is notable
grade-c Notable - See study
Notable due to mechanisms, but requires studies with reference drugs and more biomarkers measured.
grade-c Notable Moderate See 2 studies
Lone study noted a decrease from 9% to 8% with 2g spirulina, which is somewhat notable but requires more evidence to establish this.
grade-c Notable - See study
Notable as acute power output (leg extension measurement) increased by 20-30% (more efficacy in untrained persons, some efficacy in trained persons) after 8 weeks whereas placebo failed to have an increase. Needs more research to fine-tune the efficacy.
grade-c Notable - See study
The lesions were fully healed in 44% of the 1g spirulina group relative to 7% of the placebo; although no reference drug was used.
grade-c Minor Very High See 2 studies
Although increases have been noted in glutathione peroxidase and superoxide dismutase, it is difficult to assess potency thereof as there are no active controls and the two studies heterogenous.
grade-c Minor - See study
Somewhat effective, but requires more evidence; no reference drug was used to compare
grade-c Minor Moderate See all 3 studies
Reductions in blood glucose seen are not overly remarkable or noteworthy
grade-c Minor - See study
Nothing remarkable in the one study on fat oxidation rates during exercise.
grade-c Minor Moderate See 2 studies
Some various and uncertain changes in cytokines that are seen as indicators of inflammation; not enough human interventions to draw conclusions.
grade-c Minor - See study
Requires more evidence to establish its potency
grade-c Minor - See study
Although there was some promising evidence, it did not appear overly remarkable and requires further evidence.
grade-c Minor - See study
Minor increase, needs more evidence in a non-aged cohort to assess potency
grade-c - - See study
Currently insufficient evidence to support a change in RBC count.
grade-c - Very High See 2 studies
Currently not enough evidence to support any significant interaction with weight
grade-d Strong - See study
Although only based on a series of case studies at this moment in time, the reduction of liver fat seen after 3 months was remarkably effective
grade-d Notable Moderate See 2 studies
Preliminary evidence suggests the reduction of liver enzymes correlates with the degree of liver damage somewhat, and this is notable since the reduction of liver fat seen is strongly effective at this moment in time.
grade-d Notable - See study
NK cell activity against a tumor cell line (K562) increased 40% following a week ingestion of fairly reasonable oral dosing, suggesting that this is a notable increase of possible interest.
grade-d Notable - See study
The increases in mRNA content of natural killer cell content increased 37-55% (NKG2D) and 75% (perforin) which appeared to be dose-dependent, a possibly potent immunostimulatory effect.
grade-d Notable - See study
Notably effective as it trended to outperform Milk Thistle, which is a good reference supplement in regards to a sustained virologic response (not the best comparison, however)
grade-d - - See study
Currently no evidence to support an improvement in fatigue symptoms

Get access to the latest research

By becoming an Examine.com Member, you'll have access to all of the latest nutrition research on over 300 supplements across over 500 different health goals, outcomes, conditions, and more.

Research Breakdown on Spirulina

Click on any below to expand the corresponding section. Click on to collapse it.

Click here to fully expand all sections or here to fully collapse them.

Spirulina is a colloquial term for a large number of Cyanobacteria in the Spirulinaceae family.[1] The most commonly used spirulina species in dietary supplements are S. maxima and S. platensis.[1] Cyanobacteria, including spirulina, are often referred to as blue-green algae despite being prokaryotic (algae are eukaryotic).

Spirulina has been part of the human diet since at least the 16th century, when French researchers documented the consumption of sun-dried spirulina (called “Dihe”) by the native African population in modern-day Republic of Chad.[2] There is also evidence of Spirulina being harvested and traded by the Aztecs in Central America during this time.[2]

Spirulina refers to a group of cyanobacteria, the two most common being S. maxima and S. Platensis. It has been part of the human diet since at least the 16th century.

Spirulina can grow anywhere conditions allow, but is most concentrated in Lake Texcoco of Mexico, Lakes Chad and Niger of Central Africa, and along the Great Rift Valley of East Africa.[3] It thrives in high-salt (>30 g/L), alkaline (pH 9–11) waters where survival of other microorganisms is difficult or impossible.[4] Spirulina relies exclusively on photosynthesis to survive.

Most commercial production systems are based on shallow raceways in which spirulina cultures are mixed by a paddle wheel.[3] The United States of America has several of the largest intensive farms in the world, based in Hawaii and California. Other countries of major production are China, India, Thailand, Vietnam, and Taiwan.

Spirulina production has eight main stages: filtration and cleaning, preconcentration, concentration, neutralization, disintegration, dehydration, packing, and storage. These processes act to concentrate spirulina, remove its salt and water content, and prepare it for distribution.[3]

Quality control for food-standard spirulina includes microbiological standard tests, chemical composition tests, and tests for contaminants like heavy metals, pesticides, and extraneous materials (insect fragments, rodent hair, etc.).[3]

Spirulina thrives is high-salt, alkaline waters where growth for many other microorganisms is difficult. Although spirulina can be found growing in the wild, it is most commonly farmed to ensure better quality control.

On a dry-weight basis, spirulina is 60–77% protein, 9–15% lipids, and 10–19% carbohydrates, with variation depending on spirulina species and growing conditions (e.g., pond versus lab-grown).[2] The protein content is of relatively high quality for a plant-based protein, having a biological value of 75% and a digestibility of 83%.[2]

A portion of spirulina’s protein content comprises a protein-bound photosynthetic pigment called C-Phycocyanin, which has demonstrated anti-inflammatory, antioxidant, antitumor, and immunostimulating properties.[5] These effects are owed, in part, to the phycocyanobilin constituent of C-Phycocyanin, which is a close analogue of human bilirubin that functions to inhibit NADPH oxidase activity.[6] 

C-Phycocyanin comprises about 20% of spirulina’s dry weight when spirulina is freeze-dried or sun-dried, but only about 4% of dry weight when oven-dried.[7] Phycocyanobilin makes up about 5% of C-Phycocyanin, or up to 1% the dry weight of spirulina.[8] 

Spirulina also contains immunostimulatory bioactive carbohydrates, called Immulina, at 0.5–2.0% dry weight,[9] and γ-Linolenic acid (C18:3, ω6, GLA) at about 20% of the total fatty acid content (18–30 mg/g dry weight).[10] 

Spirulina is a source of several minerals, including iron (0.38–0.54 mg/g), calcium (1.48–1.8 mg/g), magnesium (2.7–3.98 mg/g), zinc (0.056–0.058 mg/g), manganese (0.024–0.033 mg/g), and copper (5–10 µg/g).[11] Spirulina also contains vitamin B12 (0.56 µg/g) and pseudovitamin B12 (7-adenyl cyanocobamide; 2.74 µg/g),[12] the latter of which is not readily usable by humans and has a binding affinity to intrinsic factor that is about one-third that of true vitamin B12.[13]

Finally, spirulina is a source of various carotenoids, including zeaxanthin (0.12–1.27 mg/g), β-carotene (0.02–2.3 mg/g), and chlorophyll a (2.6–10.8 mg/g).[14] The consumption of spirulina is positively correlated with vitamin A status in native African women,[15] and its β-carotene appears to be twice as bioavailable as that found in spinach (4.5:1 versus 9:1 ratio of β-carotene to retinol conversion).[16] Similarly, consuming 4–5 grams of spirulina is capable of increasing zeaxanthin status.[17] 

Spirulina is a high-protein food product rich in several bioactive compounds and micronutrients. It’s most well-known bioactive compound is C-Phycocyanin, which comprises about 20% of spirulina’s dry weight.

Spirulina’s spotlight role in clinical medicine is believed to be owed to its phycocyanobilin content, a compound structurally similar to unconjugated (free) bilirubin.[6] Free bilirubin is a known inhibitor of NADPH oxidase in the low nanomolar concentrations of normal physiology.[18] Phycocyanobilin also inhibits NADPH oxidase.[6]

NADPH oxidase is a free radical-generating enzyme complex activated by inflammatory cytokines and infections.[19] NADPH oxidase activation is vital for innate immunity, but excess signalling can contribute to the oxidative stress load underlying many disease states,[20] such as type-2 diabetes.[21] 

People who have genetically elevated free bilirubin levels, a clinically benign autosomal recessive disorder called Gilbert’s syndrome,[22][23] display lower rates of death from any cause (-50%) compared to the general population,[24] as well as lower levels of oxidative stress[25] and cardiovascular morbidity and mortality.[26][27] 

In animals, using drugs to increase production of free bilirubin, termed “Iatrogenic Gilbert syndrome'',[28] and administering free bilirubin directly have demonstrated benefits towards obesity, metabolic syndrome, and type-2 diabetes.[29] Several drugs have also been explored for health benefits through directly inhibiting NADPH oxidase.[30] 

Spirulina’s health effects are believed to be owed primarily to its phycocyanobilin content, which is structurally similar to bilirubin and, like bilirubin, acts to inhibit NADPH oxidase. The inhibition of NADPH oxidase reduces oxidative stress and may be an underlying factor in the health benefits associated with Gilbert’s syndrome, a condition characterized by high levels of free bilirubin.

The Dietary Supplements Information Expert Committee of the United States Pharmacopeia reviewed the safety of spirulina in 2011.[1] The committee unanimously voted for a Class A safety assignment for spirulina, meaning that available evidence did not indicate it to pose a serious health risk when properly formulated and used.

Rather, the committee noted that the primary concern with spirulina was the potential for contamination with other cyanobacteria that produce hepatotoxic and carcinogenic microcystins, as well as potential contamination with heavy metals such as mercury, cadmium, lead, and arsenic.[1] Microcystins are not produced by spirulina.

Studies in mice with unadulterated spirulina reported no adverse effects of consuming 30% of the diet from spirulina for 13 weeks,[31] or from consuming 5% of the diet as spirulina for six months.[32] 

Evidence suggests that spirulina does not pose a health risk, although it may be contaminated with things that do.

A double-blind, randomized placebo-controlled trial in adults with chronic pain reported no adverse events associated with supplementing with 2.5 grams per day of a C-phycocyanin-rich spirulina extract (40% C-phycocyanin by weight; 1 g/d) over two weeks.[33] Tests included those of blood chemistry, heart function, blood pressure, and platelet function.

One case study has documented an allergic reaction to spirulina believed to be owed to its C-Phycocyanin component.[34] The allergic reaction began within six hours of consuming 2.5 grams of spirulina, in a 14-year-old adolescent.

A case study has documented an allergic reaction to spirulina, but there appear to be no known other adverse events

Spirulina may be contaminated with toxic microcystins produced by other bacteria (not spirulina) growing in spirulina’s vicinity.[1] The safe consumption level for microcystins is set at 0.04 µg/kg/d.[35]

An early analysis of 15 commercial spirulina supplements reported that average microcystin concentrations were 0.15 µg/g (range: 0.06–0.32 µg/g) in 1998 and 0.52 µg/g (range: 0.0–2.12 µg/g) in 1999.[36] Accordingly, an 80 kg (176 lb) adult could safely consume up to 6–21 grams of spirulina (3.2 µg of microcystins) based on the two reported average contamination levels.

Quality control standards appear to have improved more recently, however, as a 2017 analysis of 14 commercial spirulina supplements reported that only 3 had detectable levels of microcystins (0.21, 0.24, and 0.84 µg/g).[37] Other recent analyses also reported that spirulina supplements from U.S.,[38] German,[39] and Italian[40] markets were free of detectable levels of microcystins.

Another contamination issue with spirulina is the accumulation of heavy metals, because spirulina has a unique ability to to chelate and neutralize toxic heavy metals, such as removing arsenic from food, water, and the environment.[1]

An analysis of 25 spirulina supplements manufactured in seven different countries (U.S., Canada, U.K., New Zealand, Japan, India, and Australia) reported that mercury and platinum concentrations were below detectable limits in most every sample.[41] Another analysis of 11 spirulina supplements from around the world found that mercury (0.02–0.11 µg/g) and cadmium (0.01–0.17 µg/g) were well below safety limits and that no lead or arsenic could be detected.[42]

This latter study also reported that pesticide contamination of spirulina was low in 3 of the 11 samples and not detected in the others, and that mycotoxins or acrylamide were undetected.[42]

Spirulina may be contaminated with hepatotoxic and carcinogenic microcystins, as well as potential with heavy metals such as mercury, cadmium, lead, and arsenic. Recent testing of commercial supplements suggests that microcystins, mycotoxins, heavy metals, and pesticides are largely a non issue.

Cyanobacteria tends to be an accumulator (biosorbent) of heavy minerals ex vivo[43][44][45] due to ion-exchange binding[46] and when applied directly to tissues with heavy metal accumulation can significantly reduce heavy metal toxicity (100mcg of spirulina hexane extract removing 89.7% of arsenic[47] which has been noted elsewhere[48]); bioactives in the hexane extract appear more potent than the alcoholic extract.[47][48]

Spirulina (250-500mg/kg) has shown efficacy in preventing mineral toxicity form occurring in pregnant rats' offsprings when the mothers were given fluoride[49] and has been noted to reduce lead accumulation in the neural tissue of rat pups from 753-828% of baseline (lead group) to 379-421% with 2% Spirulina in the diet (relative to no lead group).[50] Protective effects in pregnant rats on their pups have been noted with cadmium as well.[51]

In male rats, 300mg/kg can attenuate mercury accumulation in the testes (which is thought to partially contribute to antioxidative effects)[52] and protection against mercury has been noted elsewhere in kidneys (800mg/kg spirulina in mice).[53] The other species of cyanobacteria known as spirulina fusiformis (also a source of C-Phycocyanin[54]) appears to also possess testicular protective effects against mercury[55] and to reduce serum biomarkers of mercury toxicity[56] (similar to spirulina itself[57])

Spirulina is one of the few molecules in existence that has a body of evidence to support 'detoxifying' actions as it pertains to heavy metals, and has demonstrated this efficacy in animal models against a wide variety of minerals, including cadmium and mercury, and has been shown to be safe for pregnant rats in order to reduce the effects of mineral toxicity on rat pups

Relative to other agents, spirulina (2% of the diet) is approximately twice as effective as 5% dandelion extract in reducing lead accumulation in rat pups[50] and when 300mg/kg spirulina is compared against 400mg/kg Panax ginseng in cadmium induced testicular toxicity the effects are comparable on all accounts except spirulina increasing superoxide dismutase to a greater level[58] and seems somewhat comparable to an equal dose of Liv-52 (Ayurveda combination formula) at reducing both cadmium[59] and lead[60] toxic effects, although they were not additive.[59][60]

Relative to other agents that may reduce the biochemical harms of excess heavy metals, spirulina appears to be either greater or comparable to the other drugs

One blinded intervention has been conducted where Spirulina (250mg) paired with Zinc at 2mg was able to reduce arsenic levels in the body after persons were exposed to arsenic via drinking water.[61] Persons living in India and who were consuming arsenic via drinking water installed a filter and then were divided into placebo or Spirulina after two weeks for 14 weeks, urinary arsenic levels at baseline were 72.1+/-14.5, and 78.4+/-19.1μg/L for placebo and Spirulina respectively, decreased 72.4-74.5% after the filters in both groups, and increased to 138+/-43.6 μg/L in the Spirulina group after 4 weeks. Hair arsenic levels were 3.08+/-1.29 and 3.27+/-1.16 μg/g at baseline, and decreased 3% in placebo and 47.1% in Spirulina.[61] 

These mineral detoxifying effects have been confirmed in humans once, as pertaining to arsenic

Oral administration of spirulina to rats over the course of five weeks appears to be able to suppress CYP2C6 enzymatic activity in a manner that is not associated with a reduction in mRNA nor protein levels.[62] CYP1A2 and CYP2E1 are also downregulated, but this is associated with reductions in mRNA and protein levels.[62]

Spirulina over five weeks to rats also appears to upregulate the mRNA expression and protein content of the CYP2B1 and CYP3A1 enzymes but it was unclear if this translated to a reliable effect on overall enzymatic activity.[62]

Spirulina appears to be capable of modifying a few proteins in phase I metabolism

The proteinaceous C-Phycocyanin appears to be able to inhibit the MultiDrug Resistance Receptor 1 (MDR1) in human hepatocellular carcinoma cells. Although this one study noted an IC50 of 50uM for C-Phycocyanin and 5uM for Doxorubicin, while in the presence of 25uM C-Phycocyanin the IC50 of Doxorubicin was improved five-fold to 1uM and overall proliferation reduced further.[63] C-Phycocyanin appeared to enter the cell (seen via fluorescence) and inhibit MDR1 at the transcriptional and translational level, which increased cellular accumulation of Doxorubicin and reduced both mRNA and protein content of MDR1.[63] The mechanisms appears to be mixed via COX-2 inhibition, as it reduced PGE2 levels (which increase MDR1) which may be secondary to reducing NF-kB and AP-1 activity via NAPDH oxidase inhibition (anti-oxidant effects)[63] and has been reported elsewhere in non-carcinogenic tissue[64] and regular macrophages treated with the pro-oxidant 2-acetylaminofluorene.[65]

Other studies looking at the combination of Doxorubicin and C-phycocyanin note that the latter can prevent cardiotoxicity from the former without inhibiting its apoptotic effects on ovarian cancer cells.[66]

Spirulina may aid the kinetics of some anti-cancer drugs by mixed anti-oxidant and anti-inflammatory mechanisms, as oxidation tends to increase the amount of the MDR1 receptor, which 'boots' drugs from the cell and phycocyanin prevents this ejection

A double-blind, randomized placebo-controlled trial in adults with chronic joint pain reported significant reductions in pain at rest and when active when supplementing with 2.5 grams per day of a C-phycocyanin-rich spirulina extract (40% C-phycocyanin by weight; 1 g/d) over two weeks.[33]

One small study suggests that spirulina reduces joint pain in people with chronic joint pain.

Spirulina appears to be an NADPH complex inhibitor similar to bilirubin (the catabolite of heme which is an endogenous NADPH inhibitor; Phycocyanobilin from Spirulina has a similar structure[6] and is reduced to phycocyanorubin via the same enzyme (biliverdin reductase[67]). Beyond inhibition, spirulina has been implicated in reducing the expression of the NADPH complex (22-34% reduction in the expression of the p22phox subunit of NADPH oxidase[68]).

Spirulina's main mechanisms of action as an NADPH oxidase inhibitor and suppressor appears to have roles in neurology

A doubling of the CX3C chemokine receptor 1 (several names including fractalkine, CX3CR1, and GPR13) has been noted to be doubled in the microglia of rats relative to placebo.[69] It is thought this may play a role as, when the receptor is activated, less synthesis of proinflammatory cytokines (IL-1β and TNF-α) occurs[70] and this has also been shown to reduce microglia activation and reduce pathology of Parkinson's disease.[71]

Spirulina may increase the activity of the CX3CR1 receptor, and this appears to occur as a per se mechanism and may be independent of NADPH oxidase inhibition

Oral doses of 100mg/kg C-Phycocyanin to rats has been associated with acute protection against kainate-induced neurotoxicity in the rat hippocampus, significantly reducing microglia and astrocyte activation when measured a week after kainate injections.[72] These observed results may be secondary to kainate-induced toxicity being mediated through the pro-oxidative NADPH oxidase activation and membrane translocation[73] and the C-Phycocyanin component Phycocyanobilin inhibiting activation of this complex.[74]

Spirulina appears to be neuroprotective against excitotoxicity, possibly secondary to NADPH oxidase inhibition

Neuroprotection has also been observed in response to MPTP injections (a toxin mimicking Parkinson's Disease), where 150-200mg/kg oral Spirulina significantly attenuated dopaminergic losses in response to the toxin[75] and a similar dopaminergic toxin (6-ODHA or 6-hydroxydopamine) also appears to have its neurotoxicity reduced following 28 days of 0.1% spirulina in the diet, which outperformed 2% blueberries (anthocyanin source) for protecting from neurodegeneration in the injection site when measured at 1 week post injection (opposite trend at 4 weeks).[76]

Toxic responses to MPTP also appear to be mediated via NADPH complex activation[77][78][79] as does the toxic response to 6-hydroxydopamine,[80] although induction of fractalkine does also confer protective effects against 6-hydroxydopamine.[71]

In regards to dopaminergic (dopamine related) toxins, spirulina appears to be highly protective following oral ingestion of reasonable dosages by dual mechanisms (fractalkine induction and NADPH oxidase inhibition). Spirulina appears to be very promising for reducing the risk of developing Parkinson's Disease due to these effects

Haloperidol-induced symptoms of tardive dyskinesia in rats are also reduced with 180mg/kg spirulina daily alongside continued haloperidol injections, and doses as low as 45mg/kg when injections were ceased prior to spirulina ingestion.[81] Haloperidol has also been noted to work via excessive oxidation[82] that is produced from NADPH oxidase activation[83] and thus is tied into the main mechanism of spirulina.

Haloperidol toxicity is also protected against from spirulina due to NADPH oxidase inhibition

Spirulina at 45-180mg/kg oral intake for one week prior to ischemia/reperfusion (experimental stroke) is able to exert dose-dependent protective effects with the higher dose halving infarct size and fully normalizing parameters of lipid peroxidation and antioxidant enzymes. [84] These protective effects have been noted elsewhere with spirulina at 0.33% of the diet where it was more protective than the reference drug (2% blueberries as source of anthocyanins)[85] and 200mg/kg of isolated C-Phycocyanin for one week in gerbils prior to ischemia/reperfusion has also confirmed absolute reduction of lipid peroxidation and reduced infarct size to 4.3% of ischemic control (50mg/kg was able to reduce infarct size to 17.2% of control, also being highly effective) and normalized the neurological score after surgery when measured 24 hours later.[86]

Spirulina is able to exert protection against strokes, with 200mg/kg of isolated C-phycocyanin conferring almost absolute protection from stroke. These remarkable protective effects need to be replicated in higher mammals to draw conclusions but are incredibly promising

Iron neurotoxicity (via pro-oxidation) has also been demonstrated to be attenuated with Spirulina's C-Phycocyanin component in a SH-SY5Y neuroblastoma cell line, and using LDH leakage as indicator of cellular death Phycocyanin was able to reduce cell death from 69.10+/-2.14% in Iron-control to 28.70+/-2.56% at 500ug/mL.[87] 1000mcg/mL Spirulina (very high concentration) was demonstrated to per se induce cytotoxicity in this study.[87] This mechanism may not be related to NADPH oxidase inhibition, as spirulina is known to be a mineral chelator.

Spirulina appears to have neuroprotective effects against mineral toxicity, which may not be related to NADPH oxidase inhibition as spirulina is an effective mineral chelator (see the Pharmacology section and Mineral Detoxification)

Due to the above neuroprotective properties tied into NADPH, it is hypothesized that this enzyme plays a central role in inflammatory and oxidative neurodegenerative diseases.[8]

Spirulina has been found to nonsignificantly increase neuronal density (indicative of neurogenesis) at 0.1% of the diet despite being infected with α-synuclein,[69] a component of the protein aggregates seen in Alzheimer's and Parkinson's disease and sometimes used as a research toxin when injected.[88] The protection (assessed by TH and NeuN immunostaining) appeared to be significant in the substantia nigra,[69] an area of the brain where neurodegeneration is thought to be causative of Parkinson's.[89][90] Spirulina has also been investigated ex vivo for blocking the synthesis of beta-amyloid protein aggregates, and spirulina (EC50 of 3.76mcg/mL) outperformed all other tested food extracts including ginger (36.8mcg/mL), cinnamon (47.9mcg/mL), blueberries (160.6mcg/mL) and turmeric (168mcg/mL, diluted source of curcumin)[91] but underperformed relative to some isolated molecules such as 1,2,3,4,6-penta-O-galloyl-b-D-glucopyranose(PGG) from Paeonia suffruticosa (2.7nM), EGCG (green tea catechins) at 10.9nM, resveratrol at 40.6nM, and S-diclofenac at 10nM as comparator.[91]

One study has noted that β-amyloid pigmentation (in aged but not diseased rats of the SAMP8 line) was restored to levels similar to the non-aged mouse with 50-200mg/kg, with 200mg/kg being more effective at reducing lipid peroxidation and improving catalase activity.[92]

It is thought that microglia activation is the mechanism, as via OX-6 staining there is a reduction in microglia activation with spirulina[69] which is known to be a mechanism of α-synuclein induced neurotoxicity[93] and is dependent on NADPH oxidase activation.[94] This prevention of microglia activation has been traced back to the phycocyanobilin components in vitro[95] and reaches near absolute levels at 400mg/kg in rats (estimated human dose of 64mg/kg).[96]

Spirulina appears to have mechanisms to prevent accumulation of beta-amyloid pigmentation and alpha-synuclein (noted ex vivo) and is able to prevent these proteins from inducing inflammatory and neurotoxic effects (confirmed in rats following oral ingestion). Due to this, spirulina may have use as both therapy and prevention for Alzheimer's and Parkinson's, which requires further human evidence, but is very promising based on the animal evidence

Spirulina at low intake (5mg in rats) has been noted to attenuate the age-related increase of TNF-α[97] and in normalizing the age-related decline in memory function as assessed by the accelerated aging mouse line of SAMP8, where activity and body weight following 50-200mg/kg was normalized with the regular mouse control.[92]

The reduced rate of neurodegeneration may also apply to healthy cognitive aging, and due to less neurodegeneration, continual usage of spirulina may improve cognition in older people

Spirulina, in the diet at 0.1% in rats, appears to protect stem cells in the brain from having their proliferation reduced by inflammation (as assessed by LPS injections, likely related to Fractalkine induction or NADPH oxidase inhibition) and was shown in vitro to enhance stem cell proliferation at 0.62ng/mL and 125ng/mL.[98] The promotion of stem cell neurogenesis appears to be secondary to reducing the suppressive effects of TNF-α on proliferation, possible via Fractalkine induction.[98]

Other studies noting neuronal density over time may note some increases, including a non-significant trend to increase with 0.1% Spirulina in the diet for 4 months (rats) despite neurotoxic α-synuclein infection (in NeuN stained cells, loss was seen with TH staining).[69]

Limited evidence suggests that spirulina can promote regeneration of neurons via stem cells, which is secondary to reducing inflammation in the brain (which preserves normal regeneration rates) and has been demonstrated to occur in vivo at 0.1% of the rat diet (a very feasible human dose)

The reduced rate of neurodegeneration seen from spirulina (secondary to suppressing glial cell activation in response to toxic stressors) has been noted to improve motor function as assessed by sciatic function index (400mg/kg outperforming 800mg/kg in rats)[96] and another study using the mouse model of Amyotrophic lateral sclerosis (ALS; the mouse model is the SOD1 mouse line) noted that 10 weeks of 0.1% spirulina was able to greatly attenuate the rate of motor neuron decay when compared to control.[99] These results have been stated to be preliminary and requiring replication.[100] 

The reduced rate of neurodegeneration may apply to motor neurons as well, which would promote function and muscular control during aging and disease processes (and may also underlie the effects on power output that have been noted with spirulina). This claim requires more evidence, however

At least one study has been conducted with spirulina in a Forced Swim Test in rats, although this study used spirulina hydrolyzed by malted barley in one group.[101] Spirulina and Hydrolyzed spirulina were both significantly more effective than control at the anti-depressive model of the Forced Swim Test, but the control drug of 10mg/kg fluoxetine grealty outperformed Spirulina.[101]

Preliminary evidence suggests that spirulina could have anti-depressant actions, but they appear to be quite weak

A double-blind, randomized placebo-controlled trial in adults with chronic pain reported no significant effect on heart function (EKG) of supplementing with 2.5 grams per day of a C-phycocyanin-rich spirulina extract (40% C-phycocyanin by weight; 1 g/d) over two weeks.[33]

Spirulina doesn’t appear to affect heart function.

A meta-analysis of 4 studies reported that spirulina supplementation significantly reduced diastolic blood pressure (-7 mmHg) and tended to reduce systolic blood pressure (-3.5 mmHg) compared to control.[102] 

Rodent studies suggest that spirulina’s hypotensive effects may be owed to direct endothelium-dependent vasodilation from nitric oxide production,[103] as well as altering the balance of cyclooxygenase products such that the arachidonic acid metabolite prostacyclin is favored over thromboxane.[104] Also in rodents, combining spirulina with strength training may potentiate the hypotensive effects of spirulina.[105] 

A double-blind, randomized placebo-controlled trial in adults with chronic pain, using 2.5 grams per day of a C-phycocyanin-rich spirulina extract (40% C-phycocyanin by weight; 1 g/d) over two weeks, reported no significant difference from placebo for changes in platelet aggregation, platelet P-selectin expression, or blood clotting factors (activated partial thromboplastin time, thrombin time, and fibrinogen activity).[33] 

Mechanistically, however, C-phycocyanin appears to have a concentration-dependent effect on platelets, reducing their aggregation and clotting ability by inhibiting intracellular Ca2+ mobilization and thromboxane A2 formation.[106] 

Spirulina significantly reduces blood pressure in a meta-analysis of mostly unhealthy populations due to promoting vasodilation and nitric oxide production. Despite having the biological ability to interfere with platelet function, a controlled trial in adults suggest it doesn’t.

A study in young runners found that taking 5 grams of spirulina per day for two weeks significantly lowered post-meal triglyceride levels compared to baseline (-20%).[107] Reductions in post-meal serum triglycerides were seen at 1.5, 3, and 4.5 hours following the meal, occured in 62% of participants, and were most pronounced in participants aged 10–12 years (-30%).

A study in rats has reported that spirulina and its C-phycocyanin content inhibit both jejunal cholesterol absorption and ileal bile acid reabsorption.[108] 

Spirulina appears to inhibit the absorption of lipids.

A meta-analysis of 12 studies with 807 participants reported that spirulina supplementation significantly affected LDL-C (-33 mg/dL), triglycerides (-39 mg/dL), vLDL-C (-8 mg/dL), and HDL-C (+6 mg/dL) compared to placebo (n=7) or no intervention (n=5).[102]

Studies lasted an average of 2–12 weeks (average: 12 weeks), administered 1–19 grams of spirulina per day (average: 2 grams), and involved mostly unhealthy populations (e.g., type 2 diabetes, hypertension, and heart disease patients). Subgroup analyses suggested that blood lipid benefits were statistically significant only in trials lasted 12 weeks or longer and using 2 grams or more of spirulina.

An earlier meta-analysis of 7 studies with 522 participants found similar significant effects on LDL-C (-41 mg/dL), triglycerides (-44 mg/dL), and HDL-C (+6 mg/dL) compared to control.[109] 

Spirulina significantly lowers LDL-C, vLDL-C, and triglycerides, while raising HDL-C, in meta-analyses of mostly unhealthy populations.

In obese adults with treated hypertension, 2 g/d of spirulina for three months significantly increases insulin sensitivity (via the euglycemic-hyperinsulinemic clamp) compared to placebo.[110] Insulin sensitivity increased by 34% in the spirulina group and declined by 12% in the placebo group.

Spirulina has also shown promise as adjunct therapy to highly active antiretroviral therapy (HAART) in patients with HIV,[111] since HAART is associated with insulin resistance.[112] In HIV patients, supplementing with 19 g/d of spirulina increased glucose disposal (+56%) and insulin sensitivity (+165%) compared to control.[111]

Spirulina may increase insulin sensitivity in obese adults and patients with HIV undergoing standard care.

A meta-analysis of eight studies reported that spirulina supplementation significantly lowered fasting blood glucose by an average of 5 mg/dL.[102] No subgroup analysis was performed. Studies involved adults with type 2 diabetes (n=3), HIV (n=2), hypertension (n=1), and obesity alone (n=2); used 1–19 grams per day (median: 2 grams); and lasted 2–24 weeks (median: 12 weeks).

Spirulina may reduce fasting glucose by a clinically insignificant amount.

A meta-analysis of three studies reported that spirulina supplementation did not significantly lower HbA1c.[102] 

Spirulina may not affect HbA1c.

A study involving 25 elderly adults with type 2 diabetes reported that supplementation with 2 grams of spirulina per day for two months significantly reduced fasting blood glucose (-19 mg/dL or -12%), 2-hour postprandial glucose (-16 mg/dL or -6%), and HbA1c (-1.0%; from 9% down to 8%) compared to baseline, whereas these glycemic parameters remained unchanged in the control group.[113] No statistical analysis was performed between groups.

Another study of people with type 2 diabetes reported significant reductions in fasting and postprandial glucose levels with the use of either 1 g/d or 2 g/d of spirulina, whereas no improvements were seen in the control group.[114] However, statistical differences between groups were not performed.

However, a third study using 8 g/d of spirulina over 12 weeks reported no benefits for fasting glucose or HbA1c compared to control.[115] 

Spirulina may also benefit people with type 2 diabetes through inhibiting NADPH oxidase, which mediates the lipotoxicity of pancreatic beta-cells (that secrete insulin).[21] 

Spirulina may help people with type 2 diabetes improve their glycemic control, but research is lacking.

In a mouse model of metabolic syndrome, spirulina has been noted to reduce adipose tissue macrophage infiltration[116] (macrophages in visceral fat tend to deposit themselves and secrete inflammatory cytokines[117] which may exacerbate symptoms of metabolic syndrome[118]) which appears to be a consequence of NADPH oxidase inhibition.[118]

Secondary to NADPH oxidase inhibition and suppressing macrophage accumulation in body fat, spirulina may play a role in augmenting fat loss in people with metabolic syndrome. This mechanism is rehabilitative, and would serve no purpose in an otherwise healthy individual

100mg/kg Phycocyanin has been noted to reduce body weight in KKAy mice (genetically obese, hyperglycemic, and insulin resistant[119]) associated with a reduction in food consumption over 21 days.[120] This has been noted elsewhere where the weight reducing effects of spirulina (in mice with metabolic syndrome) was reduced 7.1% relative to metabolic syndrome control (but still 41% heavier than healthy control).[116]

In genetically obese rodents, spirulina does appear to be able to exert anti-obese effects to a small degree. It does not appear to be overly potent on this parameter

Braun lipoproteins, lipoproteins found in bacterial cell walls, may mediate aspects of the immunological aspects of Spirulina. One study found the modified amino acid 2,3-dihydroxypropylcysteine via HPLC indicative of the presence of Braun proteins,[121] while the mechanisms of Spirulina-mediated immune potentiation appear to be mediated through TLR2 receptors, of which lipoproteins are agonists of;[122] giving biological plausibility. TLR2 was found to mediate the effects of Spirulina as cells expressed TLR2 showed NF-kB activation in response to Spirulina and those expressing MD-2 and TLR4 failed to do so, although this study attributed the observed effects to polysaccharides.[123]

Inhibition of NF-kB has been noted elsewhere in both macrophages and splenocytes at 100μg/mL of the lipid extract.[124]

The polysaccharide components are also known to activate the immune system (similar to polysaccharides from Panax Ginseng and Ganoderma Lucidum), this polysaccharide has been named Immulina or Immolina,[9] which may draw confusion as this is also a patented name for a Spirulina product.[121][125] This polysaccharide, at concentrations between 1ng/mL to 100ug/mL, increased the mRNA levels of various tested chemokines (IL-8, MCP-1, MIP-1a, IP-10), and doses as low as 1ng/mL induced mRNA of TNF-α and 100ng/mL to induce IL-1β; the induction of these mRNAs was lesser than LPS, and Immolina did not influence cell viability or differentiation.[126]

Some mechanisms related to the immune system are due to compounds acting as ligands to immune cell receptors and activating these cells. The low concentrations needed suggest that these mechanisms are active in vivo

Conversely to the pro-inflammatory aspects above, the biliprotein C-Phycocyanin acts as a selective COX-2 inhibitor (which is associated to some of its benefits against colon cancer[127][128]) and incubation with activated macrophages (via LPS) with C-phycocyanin can result in macrophage apoptosis via COX-2 inhibition (which is induced by LPS).[129] The inhibitory potential of C-phycocyanin is potent with an IC50 value of 180nM,[130] and it can technically inhibit COX-1 as well but the IC50 value is higher at 4.47uM, and has the ratio of COX1/COX2 inhibition is 0.04 and thus selective.[130] On a molar basis, C-phycocyanin was more inhibitory of COX2 than celecoxib (IC50 260nM) and Refecoxib (IC50 400nM) although the latter two drugs were more selective (0.015 and lesser than 0.0013).[130] The inhibitory potential of Phycocyanin is reduced to 9.7uM when the molecule itself is reduced (after accepting electrons, its anti-oxidant mechanism).[130]

Secondary to COX-2 inhibition and possibly other anti-inflammatory actions (iNOS inhibition), 20-50mg/kg injections of Phycocyanin appears to significantly and acutely (one injection) reduce circulating chemokines such as PGE2 and TNF-α that are stimulated in response to pro-inflammatory stimuli, and pain-relieving effects are also observed (but 50mg/kg Phycocyanin is outperformed slightly by Ibuprofen at the same dose).[131]

Despite these predominately anti-inflammatory (and possibly immunosuppressant) activites noted above, isolated Phycocyanin has been noted to enhance adaptive immunity in mice. This study noted that oral ingestion of Spirulina for 6 weeks was able to, after mice were primed with the antigen (molecule that adaptive immunity 'locks on' to) that an increased amount of total and antigen-specific Immunoglobulin A (IgA) while suppressing allergenic IgE secretion.[132]

The anti-oxidant effects of NADPH oxidase inhibition (seen mostly in the neurology section and liver section) also appear to influence anti-inflammatory effects because of the selective COX-2 inhibitor compound

Two pilot studies (unblinded) using Spirulina at 400mg daily (but with a higher concentration of Braun lipoproteins, those found in gram-negative bacteria cell walls) noted that Natural Killer (NK) cell activity increased by 40% as assessed by tumor killing ability (one study) and mRNA production of NK cells increased by 37-55% (200mg and 400mg, respectively) after a week of supplementation; this study did recieve a grant from the company supplying the Spirulina, however.[121] Enhanced NK cell cytotoxicity (function) has been noted elsewhere with a Spirulina hot water extract.[133]

A handful of studies on the subject do suggest that spirulina can increase natural killer (NK) cell activity in the body after a relatively low-dose ingestion

In animals, the increase in NK cell activity appears to be mediated via Myeloid differentiation primary response gene (MyD88) which is in the TLR4 activation pathway, as abolishing this protein abolishes the NK activation seen with Spirulina.[134] Spirulina was also synergistic with a MyD88 inducer in this study, despite the inducer not having any ability to boost NK activity per se, and this study noted that with 0.1% Spirulina hot water extract added to food that NK activity increased in 2 weeks.[134]

The induction of NK cell activity may be non-selective mediated via toll-like receptors, as abolishment of either TLR2 or TLR4 does not diminish the NK enhancing activity of Spirulina but double-abolishment does.[134] Although TLR3-TICAM-1 can induce natural killer cell activation,[135] TICAM-1-/- mice do not appear to reduce the efficacy of Spirulina.[134]

Spirulina appears to work via a TLR2/4 pathway that is dependent on MyD88

Some studies measure serum Myeloperoxidase (MPO) as a biomarker of Neutrophil activation, and find dose-dependent reductions in serum MPO with near abolishment of oxidative stress-induced MPO increases at 6g/kg Spirulina in rats.[136]

Lower doses (25-100mg/kg) are associated with significantly attenuated MPO induction (by alloxan), but not abolishment.[137]

200mg/kg and 400mg/kg Spirulina daily to rats injected with collagen (to induce arthritis) and then fed Spirulina over the course of 45 days showed normalized joint histopathology (visual inspection under microscope) and normalized biochemical markers such as lipid peroxidation.[138] The rats fed 400mg/kg, after visual inspection, appeared to be not significantly different than control rats while 200mg/kg still possessed some visual arthritic symptoms.[138] This higher dose has also been associated with normalizing motor function in response to collagen injections, although this mechanism was thought to be secondary to suppressing glial cell activation (an anti-inflammatory effect).[96]

This anti-arthritic effect has been noted elsewhere with 800mg/kg oral intake Spirulina (chosen as preliminary testing suggested it was more potent than 200, 400, and 600mg/kg) noted that Spirulina was able to reverse the pro-arthritic trend of a test drug in as little was a week[139] and acted to almost completely normalize β-Glucuronidase and β-galactosidase in the liver, spleen, and plasma to control levels which not changing these parameters in a Spirulina fed control.[139] Another study using a zymosin-induced arthritic model using 100 and 400mg/kg Spirulina orally noted that the expected increase in β-Glucuronidase was inhibited 78.7% and 89.2%, respectively. When using 10mg/kg Triamcinolone as a reference drug, it inhibited 94.1% and was seen as nonsignificantly more potent than 400mg/kg Spirulina.[140] Protective effects were seen via histology, with 400mg/kg outperforming 100mg/kg and the reference drug being most effective.[140]

Preliminary evidence in animals suggests that spirulina is a potent anti-arthritic agent, and at least two studies suggest that toxin-induced arthritis is almost normalized in lab rats. It appears to be of similar or slightly lesser potency than Triamcinolone (pharmaceutical corticosteroid)

2g of Spirulina for half a year (6 months) in adults (30.1+/-6.69) with allergic rhinitus (nasal allergies) was associated with a highly significant improvement in subjective symptoms such as reduced frequency of nasal discharge, nasal congestion, and nasal itching and sneezing.[141] On a rating scale of 1-10 with how satisfied participants were with the treatment, spirulina rated on average 7.21+/-1.01 (how satisfied) and 7.44+/-0.89 (how effective) while placebo rated 3.40+/-1.71 and 3.54+/-1.37, respectively.[141] Similar beneficial results have been reported elsewhere, where 1-2g of Spirulina over 12 weeks noted that immune cells isolated from the persons ingesting 2g daily had suppressed secretion of the pro-inflammatory cytokine IL-4 in response to an antigen.[142]

One study on elderly (60-87yrs; n=78) noted that 8g of Spirulina daily for 16 weeks (4 months) was associated with an increase in IL-2 (144% in men, 146% in females) and alterations in IL-6 (down to 73.4% of control in men, up to 176% in females), the altered ratio being seen as anti-inflammatory.[143] TNF-α also trended to decline in both groups, and MCP-1 in females.[143] This currently is the only study to measure baseline cytokines (biomarkers of inflammation), with other human interventions of moderate quality all suggesting an improvement of natural killer cell activity.[121][133]

There is currently limited evidence in humans when examining all parameters, but spirulina shows some early trends of increasing natural killer cell activity while concurrently lowering systemic inflammation

In rats, reductions of TNF-α have been noted at doses as low as 25mg/kg bodyweight basic Spirulina extract.[137]

Spirulina, in general, can protect cells from death via its anti-oxidative properties if the death to the cell was caused by oxidative means; general anti-oxidant properties.[144] In a comparative study against Vitamin C, it was noted that Spirulina was able to reduce free-radical induced death by 2-5 fold, but was less effective than vitamin C at the same concentrations tested (125, 250mcg/mL).[144]

A comparative study between Spirulina and Wheat Grass (Triticum aestivum) at 500mg twice daily for 30 days demonstrated that both compounds had anti-oxidative capacities, but the changes were greater with Wheat Grass and failed to reach significance with Spirulina.[145] MDA, plasma Vitamin C, and intrinsic anti-oxidant enzymes were assessed.[145]

In a rat model of testicular toxicity, Spirulina is able to preserve testosterone levels despite oxidative toxins while the group given Spirulina without the toxin (mercury) did not experience an increase in testosterone.[52]

A study in obese mice (secondary to fatty liver) noted that Spirulina was able to decrease circulating leptin levels closer to lean control levels when compared to obese control and obese rats given 0.02% pioglitazone.[116]

In a rat model of cyclophosphamide-induced mutagenicity Spirulina at 200, 400, and 800mg/kg for 2 weeks prior to 5 consecutive days of cyclophosphamide was tested and the anti-mutagenic/anti-genotoxic effects investigated.[146] The increase in implantation losses in pregnant mice was significantly reduced at all doses and normalized the sperm abnormalities seen with the toxin (sperm count, motility, shape).[146]

In studies that measure DNA fragmentation in healthy cells in response to toxins (a process seen as carcinogenic), Spirulina at 50mg/kg is able to reduce a 31.2% increase in DNA fragmentation by aflatoxin to 8.8% in the liver and reduced a 10.2% increase to 0.9% in the testes; this study noted that Spirulina reduced DNA fragmentation by 1.3% in the liver when no toxin was ingested, and the protective effects were nonsignificantly additive with whey protein.[147]

Spirulina appears to have the capacity to reduce tumor size or otherwise retard tumor growth rates secondary to increasing Natural Killer cell activity,[134] although other studies note reduction in tumor size and do not draw a link between said observation and NK cells.[148]

One intervention in Kerala India measuring oral leukoplakia in tobacco users noted that 1g Spirulina daily for a year was associated with complete regression of lesions in the oral cavity in 45% of persons in this group, relative to 7% in placebo; upon cessation of supplementing Spirulina, 9 of the 20 responders developed the lesions the following year without Spirulina.[149]

Low dose spirulina (1g) has been noted to decrease the rate of oral lesions in tobacco users, although it did not confer complete protection to all participants

One in vitro study investigating the polysaccharide of Spirulina known as Calcium Spirulin noted that B16-BL6 Melanoma cells had 50% reduced invasion (Matrigel/fibronectin-coated filters) at 10mcg/mL concentration, and reduced migration to laminin (but not fibronectin) filters in a dose-dependent manner; similar effects were noted with colonic M3.1 and fibrosarcoma HT-1080 cells.[150]

C-phycocyanin (from the protein fragment of Spirulina) is associated with protecting from colon cancer in part due to its ability to inhibit excessive production of COX-2 in colon cells,[151] which tends to be increased in colon cancer cells.[127] Many studies pair C-Phycocyanin with Piroxicam, which is a nonselective COX1/2 inhibitor, and the benefits appear additive.[128][152][153]

Daily injections of 200mg/kg C-Phycocyanin can normalize Akt/PI3k activation and concurrently raise PTEN and GSK-3β activation,[128] which is additive with the NSAID inhibitor Piroxicam, where 4mg/kg Piroxicam and 200mg/kg C-Pycocyanin inhibited 92.33% of colonic inflammation in response to the toxin dimethylhyadrazine (DMH), with C-Phycocyanin itself inhibiting 72.33% of inflammation (more effective than 4mg/kg Piroxicam at 62.33% and 5mg/kg Indomethacin at 67%)[153] and reduced the amount of abberant crypt foci (indicative of polyp formation) by 65% in isolation, and 75% with Piroxicam.[153] This same dose of C-Phycocyanin (200mg/kg) also reduced DMH lesion incidence from 100% to 66% over 6 weeks of treatment, acted to normalize histological changes, and was found to increase the amount of apoptotic cells from approximately 7% to 30% (data derived from graph, similar potency to 4mg/kg Piroxicam and combination is additive).[152]

In studies measuring cell colonies, less aggregation is noted following both C-Phycocyanin and Piroxicam (Spirulina nonsignificantly more effecitive, reducing the DMH control of 57.49% to 16.53%) and both antiinflammatories increase cell count in early (from 3.34% in DMH control to 20.43% with C-Phycocyanin) or late (2.45% to 33.66%) stage apoptosis.[128]

C-Phycocyanin is able to exert a large protective degree against 1,2-dimethylhyadrazine induced carcinogenesis, which is slightly (sometimes nonsignificantly) more effective than 4mg/kg Piroxicam when 200mg/kg C-Phycocyanin is used, additive with Piroxicam

A study conducted in young rats (30 day old pups) comparing a diet with 17% Spirulina (64% protein by weight) against 17% casein protein (84% protein by weight) as the sole protein source over the course of 60 days noted that although total muscle weight, size, and DNA content were similar in both groups that Spirulina had 44% higher levels of the contractile protein Myosin, suggestive of increased protein synthesis rates relative to casein.[154] No significant differences were observed in the Actin protein component.[154]

Though too preliminary to guess how it would work in humans, there appears to be a more hypertrophic effects from the spirulina protein source in young rat pups when compared to casein protein

One study on untrained university students as well as trained (3 years of activity or greater) noted that Spirulina, taken at 2g daily for 8 weeks, found increased peak force output in both the trained and untrained subjects that used Spirulina alongside training (relative to placebo combined with training) but no significant influence was seen on muscular endurance as assessed by 60 second isometric.[155] Dietary analysis' were not conducted in this study.

Only one human study was conducted in power output, which showed improvement, but a lack of dietary analysis precludes any conclusions that could be drawn from this

A study conducted in healthy youth (20-21yrs) noted that 3 weeks of supplementation with Spirulina at 7.5g daily (2.5g taken with a meal thrice a day; 53.3% protein and 33.3% carbohydrate) was associated with an increased time to exhaustion as assessed by treadmill running.[156] While placebo improved their times by 23 seconds at follow-up (3.2% improvement) Spirulina was associated with an increase of 52 seconds (7.3%).[156] This study also noted significantly less lactate dehydrogenase (79.3% of control) and more lactate (138% of control) when blood was taken 30 minutes after exercise, although a high interindividual range existed.[156] The only other study to measure lactate was at complete rest, and noted a non-significant trend to increase in runners.[107]

These results have been replicated, as 6g of Spirulina for 4 weeks was associated with an improved time to exhaustion (131% of control) after subjects were pre-exhausted with a 2 hour run; this study was conducted in moderately trained athletic men, and this was thought to be secondary to the increase in fat oxidation (+10.9%) preserving carbohydrate storages (glucose oxidation decreased by 10.3%).[157]

Spirulina has repeatedly shown to improve endurance exercise performance at practical doses in human subjects that are otherwise healthy

In a series of case studies with Spirulina (4) where each patient was their own cross-over ontrol, it was suggested that Spirulina at 3g daily for 4 weeks did not possess the ability to aid in idiopathic (without disease state) chronic fatigue.[158]

A study in rats in which said ovariectomized rats (a model to mimic menopause) fed Spirulina at 80mg/kg, 800mg/kg or 4g/kg bodyweight with 0.2% calcium (by weight in diet) and compared to a Spirulina free diet noted that no differences in body weight existed (despite increases in food intake with Spirulina) and Spirulina was associated with a decrease in bone mineral density under estrogen deficient conditions.[159]

The anti-oxidative effects of Spirulina at 1g/kg oral ingestion for 5 days prior to a cisplatin injection was able to attenuate damage to the liver (histological examination) and combining Spirulina with 500mg/kg Vitamin C appeared to abolish cisplatin-induced liver damage.[160] Protective effects on the liver from toxins have also been established against D-galactosamine and Acetominophen with 3-9% dietary Spirulina in rats.[161]

One rodent study on fructose-induced insulin resistance noted that Spirulina at low doses (0.33g/kg in rats) was associated with decreased SGOT (-33.42%) and SGPT (-24.78%) levels in serum, their increase of which indicates hepatocellular necrosis and membrane damage and their reduction indicative of less liver cell damage.[162] Reductions in SGOT and SGPT have been noted in humans, but after 2 or 4g Spirulina for 3 months they were from 21.1 to 16.7 (-20.9%) with 2g and 19.4 to 15.5 (-20.1%) with 4g and both were not statistically significant in these otherwise healthy persons with elevated cholesterol, as placebo also saw a decrease of 18.8%.[163]

Spirulina attenuated the increase in liver enzymes (ALP, AST, ALT) in response to Cisplatin injections while the combination of Spirulina (1g/kg) and Vitamin C (500mg/kg) effectively normalized levels of liver enzymes.[160] These particular enzymes have also been noted to be reduced following oxidative damage paired with a high fat diet, where 2-6g Spirulina dose-dependently reduced both ALT and AST.[136]

It has been hypothesized that Spirulina, via NADPH oxidase inhibition, could inhibit proliferation of stellate cells and serve as a therapeutic alternative in instances of liver fibrosis.[164] This hypothesis is based on suppression of stellate cell proliferation by activation of the ERb receptor (via one of the soy isoflavones Genistein[165] and in part estrogen itself[166]) working vicariously through suppressing NADPH oxidase activity, as well as DPI (a research chemical that inhibits NADPH activity) has also been shown to reduce stellate cell proliferation.[167][168]

Spirulina has the ability to reduce fatty liver (steatohepatitis) in various animal models, including fructose-induced obese rats,[162], MSG-induced obese rats (where cerebral injections of MSG into newborn rats induces fatty liver via overeating[169]),[116] choline-deficient high fat diet injected with a pro-oxidant (2-6g/kg Spirulina).[136]

Studies that compare Spirulina to reference drugs or practises note that Spirulina (5% of feed intake) being more effective than 0.02% pioglitazone at reducing hepatic triglyceride content and cholesterol,[116] 17% Spirulina (very high dose) being more effective than minor cardiovascular exercise at improving lipid profiles with additive benefits to lowering cholesterol (similar reductions in liver fat between groups at 43-46% of control),[170]

Spirulina may also act in a preventative manner, where the increase in liver fat in response to a high fat, cholesterol, and alcohol diet with additional statin drugs was halved with Spirulina supplementation.[171]

In rats, spirulina shows rehabilitative and preventative mechanisms to reduce liver fat buildup. The effect seems potent

These mechanisms have been tested in humans, and in a series of case studies where three persons were treated with 4.5g Spirulina for 3 months each and later assessed by ultrasound found an average decrease in ALT by 41%, including the third case where the pathological level of ALT was reduced 34%.[172] Triglycerides, total cholesterol, LDL-C, and the cholesterol:HDL-C ratio all decreased on average by 19%, 16%, 22% and 18%; respectively. This was thought to be secondary to universal improvements in the levels of fatty liver seen via ultrasound (biopsies not taken).[172]

Spirulina may be able to reduce fatty liver build-up as induced by the diet and appears to be quite potent at doing so independent of lifestyle changes (and even with combined statin and alcohol usage in rats), with limited human evidence showing just as promising results. It appears to be quite moderately potent, but quite reliable

Components of Spirulina appear to hold relatively general anti-viral effects in vitro, with relative affinity for the herpes simplex virus with an EC50 of 0.069mg/mL.[173]

In a trial of persons with chronic hepatitis C infection, Spirulina was compared against Silymarin (isolated from Milk Thistle) and both treatments had a degree of efficacy at inducing a sustained virological response (suppression of the virus to undetectable levels); Spirulina trended to be better than Silymarin but was not statistically significant.[174] In this 6 month trial, 4 persons (13.3%) achieved a sustained virological response while 2 others (6.7%) had partial benefits and the other 80% not responding; Silymarin only had one sustained virological response (3.4%) and the rest did not response.[174] Responders had low baseline viremia. Another study on HIV failed to notice any benefit to abnormal liver enzymes associated with Spirulina[175] and a third pilot study combining Spirulina with Undaria Pinnatifida (common source of fucoxanthin) noted that with the HIV/AIDS virus that quality of life improved after 3 weeks of either supplement of combination therapy (of 2.5g Undaria and 3g Spirulina), and a sole subject (case study) used treatment for a year and reduced his virologic load while increasing CD4+ immune cell count from 474 to 714 CD4/uL (+50%).[176] 

The anti-viral effects of spirulina appear to be active after human consumption despite spirulina's non-toxicity at tested doses of up to 5g, and may confer some symptom relief associated with viral disorders over the short term or act in opposition of the virus over the longer period. There is not enough evidence to suggest reliability of treatment
Although spirulina appears to be one of the more potent supplements for improving virological status (based on preliminary evidence at least), this does not appear to be a topic where nutritional supplementation holds much potency

One study has been conducted in older persons with a history of anemia taking 3g of Spirulina daily for 12 weeks failed to note an increase in red blood cell count yet increased mean corpuscular hemoglobin (MCH), MCV, and MCHC in men and increased in MCH in women.[177] Platelets were unchanged over 12 weeks, and white blood cells increased significantly at 6 weeks in time; high variability noted in this study.[177]

Spirulina may aid anemic symptoms, but evidence is preliminary

Thymus atrophy can be induced by Tributyltin via pro-oxidative means, which can be almost abolished when the C-phycocyanin from Spirulina is pre-loaded (this study, however, used injections) of 70mg/kg bodyweight.[178] Although control had reduced size to 30% of untreated control, coingestion of the toxin and C-phycocyanin had 90% control size, and the protection was hypothesized to be secondary to the antioxidative abilities of C-phycocyanin.[178]

C-Phycocyanin and/or Spirulina are able to protect the kidneys from from various toxic insults including mercury chloride (reducing grade 4 histology damage to 'minor' damage at 100mg/kg C-Phycocyanin[179]), cisplatin (50mg/kg C-Phycocyanin),[180][181] cyclophosphamide (1,000mg/kg of spirulina),[182] 4-nitroquinoline-1-oxide (500mg/kg Spirulina),[183] and Gentamycin.[184] These renal toxins exert their damage via oxidative stress.

C-Phycocyanin appears to be highly protective of the kidneys via various toxin-induced stressors, with combined anti-inflammatory and anti-oxidative mechanisms

Heptadecane (volatile) has also been implicated in preserving renal function in isolation at 2-4mg/kg in rats, where the increase in reactive oxygen species (ROS; inherent in vivo and induced by t-BHP in vitro) and NF-kB activity seen with aging were normalized in a dose-dependent manner, and in vitro the oxidation-induced NF-kB activity was slightly attenuated at 1-20µM.[185]

Heptadecane may also be a bioactive of interest, but appears to be less potent than C-Phycocyanin

The fibrotic effects of paraquat toxicity can be alleviated with 50mg/kg C-Phycocyanin in rats.[186]

The oxidative damage to the testes induced by mercury has been noted to reduce serum and testicular lipid peroxidation at 300mg/kg spirulina intake, which was associated with less (35%) mercury accumulation in the testes.[52] This study also noted that, relative to untreated control, the group given Spirulina in isolation experienced increases in oxidative enzymes (6.3% SOD and 9.2% GSH) with reductions in blood lipid peroxidation (14.8%).[52]

The combination of Spirulina and Whey Protein concentrate was because due to both being complete protein sources, Spirulina is relatively low in the amino acid Cysteine whereas many of Whey Protein's benefits are secondary to being a high source of Cysteine. In a study where 2.5mg/kg Spirulina and 300mg/kg Whey Protein were consumed either in isolation or combined for 30 days, it was found that Whey Protein was nonsignificantly better at reducing lipid peroxidation in the liver and testes and the combination conferred no additional benefits while the combination conferred non-significant benefits to improving glutathione status in these organs.[147] Both were effective in reducing pathology associated with aflatoxin infection as well, with minor differences and little additive effects.[147]

A whey-spirulina mix may be a good combination to round out dietary amino acids, but it is less than additive in regards to anti-oxidation in the liver

NT-020 is a combination of polyphenols from blueberry, green tea catechins, carnosine (from beta-alanine) and Vitamin D[187][188] and this combination supplement appears to be synergistic with spirulina in enhancing stem cell proliferation (CD34+ derived bone marrow cells). Although the exact molecule(s) mediating the synergism are not known, it was calculated at being 50% greater than the additive benefits.[98] The mechanism of synergism appeared to be via spirulina suppressing TNF-α induced suppression of stem cell proliferation, while some other agent was able to induce stem cell proliferation (and worked better when TNF-α could not act).[98] NT-020 overall is known to do this[189][190] in a synergistic manner itself[187] with all bioactives being somewhat active (hypothesized to be secondary to reducing oxidative stress[187]).

Spirulina is able to suppress the actions of a negative regulator of stem cell proliferation, which allows the nutraceutical combination of NT-020 to induce stem cell proliferation. Due to this and all bioactives of NT-020 being active, spirulina is likely synergistic with all individuals components (blueberries, carnosine, green tea, and vitamin D)

References

  1. ^ a b c d e f Marles RJ, et al. United States pharmacopeia safety evaluation of spirulina. Crit Rev Food Sci Nutr. (2011)
  2. ^ a b c d Ciferri O. Spirulina, the edible microorganism. Microbiol Rev. (1983)
  3. ^ a b c d Habib MA, et al. A review on culture, production and use of spirulina as food for humans and feeds for domestic animals and fish. FAO Fisheries and Aquaculture Circular. (2008)
  4. ^ Kebede E, Ahlgren G. Optimum growth conditions and light utilization efficiency of Spirulina platensis (= Arthrospira fusiformis) (Cyanophyta) from Lake Chitu, Ethiopia. Hydrobiologia. (1996)
  5. ^ Liu Q, et al. Medical Application of Spirulina platensis Derived C-Phycocyanin. Evid Based Complement Alternat Med. (2016)
  6. ^ a b c d McCarty MF. Clinical potential of Spirulina as a source of phycocyanobilin. J Med Food. (2007)
  7. ^ Chaiklahan R, et al. Separation and purification of phycocyanin from Spirulina sp. using a membrane process. Bioresour Technol. (2011)
  8. ^ a b McCarty MF, Barroso-Aranda J, Contreras F. Oral phycocyanobilin may diminish the pathogenicity of activated brain microglia in neurodegenerative disorders. Med Hypotheses. (2010)
  9. ^ a b Pugh N, et al. Isolation of three high molecular weight polysaccharide preparations with potent immunostimulatory activity from Spirulina platensis, aphanizomenon flos-aquae and Chlorella pyrenoidosa. Planta Med. (2001)
  10. ^ Colla LM, Bertolin TE, Costa JA. Fatty acids profile of Spirulina platensis grown under different temperatures and nitrogen concentrations. Z Naturforsch C. (2004)
  11. ^ Li ZY, et al. Effects of electromagnetic field on the batch cultivation and nutritional composition of Spirulina platensis in an air-lift photobioreactor. Bioresour Technol. (2007)
  12. ^ Watanabe F, et al. Characterization and bioavailability of vitamin B12-compounds from edible algae. J Nutr Sci Vitaminol (Tokyo). (2002)
  13. ^ Watanabe F, et al. Pseudovitamin B(12) is the predominant cobamide of an algal health food, spirulina tablets. J Agric Food Chem. (1999)
  14. ^ Park WS, et al. Two Classes of Pigments, Carotenoids and C-Phycocyanin, in Spirulina Powder and Their Antioxidant Activities. Molecules. (2018)
  15. ^ Soudy ID, et al. Vitamin A status in healthy women eating traditionally prepared spirulina (Dihé) in the Chad Lake area. PLoS One. (2018)
  16. ^ Wang J, et al. Vitamin A equivalence of spinach beta-carotene in human body. Wei Sheng Yan Jiu. (2007)
  17. ^ Yu B, et al. Spirulina is an effective dietary source of zeaxanthin to humans. Br J Nutr. (2012)
  18. ^ Hinds TD Jr, Stec DE. Bilirubin, a Cardiometabolic Signaling Molecule. Hypertension. (2018)
  19. ^ Panday A, et al. NADPH oxidases: an overview from structure to innate immunity-associated pathologies. Cell Mol Immunol. (2015)
  20. ^ Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. (2007)
  21. ^ a b McCarty MF, Barroso-Aranda J, Contreras F. NADPH oxidase mediates glucolipotoxicity-induced beta cell dysfunction--clinical implications. Med Hypotheses. (2010)
  22. ^ Olsson R, Stigendal L. Clinical experience with isolated hyperbilirubinemia. Scand J Gastroenterol. (1989)
  23. ^ Kulkarni RG, et al. Gilbert's syndrome in healthy blood donors what next??. Asian J Transfus Sci. (2016)
  24. ^ Horsfall LJ, et al. Gilbert's syndrome and the risk of death: a population-based cohort study. J Gastroenterol Hepatol. (2013)
  25. ^ Maruhashi T, et al. Hyperbilirubinemia, augmentation of endothelial function, and decrease in oxidative stress in Gilbert syndrome. Circulation. (2012)
  26. ^ Kundur AR, Singh I, Bulmer AC. Bilirubin, platelet activation and heart disease: a missing link to cardiovascular protection in Gilbert's syndrome?. Atherosclerosis. (2015)
  27. ^ Goel A, Aggarwal R. Unconjugated hyperbilirubinemia: a blessing in disguise?. J Gastroenterol Hepatol. (2013)
  28. ^ McCarty MF. ''Iatrogenic Gilbert syndrome''--a strategy for reducing vascular and cancer risk by increasing plasma unconjugated bilirubin. Med Hypotheses. (2007)
  29. ^ DiNicolantonio JJ, McCarty MF, O'Keefe JH. Antioxidant bilirubin works in multiple ways to reduce risk for obesity and its health complications. Open Heart. (2018)
  30. ^ Altenhöfer S, et al. Evolution of NADPH Oxidase Inhibitors: Selectivity and Mechanisms for Target Engagement. Antioxid Redox Signal. (2015)
  31. ^ Salazar M, et al. Subchronic toxicity study in mice fed Spirulina maxima. J Ethnopharmacol. (1998)
  32. ^ Yang Y, et al. In vitro and in vivo safety assessment of edible blue-green algae, Nostoc commune var. sphaeroides Kützing and Spirulina plantensis. Food Chem Toxicol. (2011)
  33. ^ a b c d Jensen GS, et al. Clinical Safety of a High Dose of Phycocyanin-Enriched Aqueous Extract from Arthrospira (Spirulina) platensis: Results from a Randomized, Double-Blind, Placebo-Controlled Study with a Focus on Anticoagulant Activity and Platelet Activation. J Med Food. (2016)
  34. ^ Petrus M, et al. First case report of anaphylaxis to spirulin: identification of phycocyanin as responsible allergen. Allergy. (2010)
  35. ^ Dietrich D, Hoeger S. Guidance values for microcystins in water and cyanobacterial supplement products (blue-green algal supplements): a reasonable or misguided approach?. Toxicol Appl Pharmacol. (2005)
  36. ^ Gilroy DJ, et al. Assessing potential health risks from microcystin toxins in blue-green algae dietary supplements. Environ Health Perspect. (2000)
  37. ^ Roy-Lachapelle A, et al. Detection of Cyanotoxins in Algae Dietary Supplements. Toxins (Basel). (2017)
  38. ^ Marsan DW, et al. Evaluation of microcystin contamination in blue-green algal dietary supplements using a protein phosphatase inhibition-based test kit. Heliyon. (2018)
  39. ^ Heussner AH, et al. Toxin content and cytotoxicity of algal dietary supplements. Toxicol Appl Pharmacol. (2012)
  40. ^ Vichi S, et al. Contamination by Microcystis and microcystins of blue-green algae food supplements (BGAS) on the Italian market and possible risk for the exposed population. Food Chem Toxicol. (2012)
  41. ^ Al-Dhabi NA. Heavy metal analysis in commercial Spirulina products for human consumption. Saudi J Biol Sci. (2013)
  42. ^ a b Muys M, et al. High variability in nutritional value and safety of commercially available Chlorella and Spirulina biomass indicates the need for smart production strategies. Bioresour Technol. (2018)
  43. ^ Doshi H, Ray A, Kothari IL. Biosorption of cadmium by live and dead Spirulina: IR spectroscopic, kinetics, and SEM studies. Curr Microbiol. (2007)
  44. ^ Solisio C, et al. Cadmium biosorption on Spirulina platensis biomass. Bioresour Technol. (2008)
  45. ^ Cain A, Vannela R, Woo LK. Cyanobacteria as a biosorbent for mercuric ion. Bioresour Technol. (2008)
  46. ^ Fang L, et al. Binding characteristics of copper and cadmium by cyanobacterium Spirulina platensis. J Hazard Mater. (2011)
  47. ^ a b Saha SK, Misbahuddin M, Ahmed AU. Comparison between the effects of alcohol and hexane extract of spirulina in arsenic removal from isolated tissues. Mymensingh Med J. (2010)
  48. ^ a b Saha SK, et al. Effect of hexane extract of spirulina in the removal of arsenic from isolated liver tissues of rat. Mymensingh Med J. (2005)
  49. ^ Banji D, et al. Investigation on the role of Spirulina platensis in ameliorating behavioural changes, thyroid dysfunction and oxidative stress in offspring of pregnant rats exposed to fluoride. Food Chem. (2013)
  50. ^ a b Gargouri M, et al. Spirulina or dandelion-enriched diet of mothers alleviates lead-induced damages in brain and cerebellum of newborn rats. Food Chem Toxicol. (2012)
  51. ^ Paniagua-Castro N, et al. Spirulina (Arthrospira) protects against cadmium-induced teratogenic damage in mice. J Med Food. (2011)
  52. ^ a b c d El-Desoky GE, et al. Improvement of Mercuric Chloride-Induced Testis Injuries and Sperm Quality Deteriorations by Spirulina platensis in Rats. PLoS One. (2013)
  53. ^ Sharma MK, et al. Evaluation of protective efficacy of Spirulina fusiformis against mercury induced nephrotoxicity in Swiss albino mice. Food Chem Toxicol. (2007)
  54. ^ Madhyastha HK, et al. Purification of c-phycocyanin from Spirulina fusiformis and its effect on the induction of urokinase-type plasminogen activator from calf pulmonary endothelial cells. Phytomedicine. (2006)
  55. ^ Saxena PS, Kumar M. Modulatory potential of Spirulina fusiformis on testicular phosphatases in Swiss albino mice against mercury intoxication. Indian J Exp Biol. (2004)
  56. ^ Sharma MK, et al. Modification of mercury-induced biochemical alterations in blood of Swiss albino mice by Spirulina fusiformis. Environ Toxicol Pharmacol. (2005)
  57. ^ Simsek N, et al. Spirulina platensis feeding inhibited the anemia- and leucopenia-induced lead and cadmium in rats. J Hazard Mater. (2009)
  58. ^ Karadeniz A, Cemek M, Simsek N. The effects of Panax ginseng and Spirulina platensis on hepatotoxicity induced by cadmium in rats. Ecotoxicol Environ Saf. (2009)
  59. ^ a b Jeyaprakash K, Chinnaswamy P. Effect of spirulina and Liv-52 on cadmium induced toxicity in albino rats. Indian J Exp Biol. (2005)
  60. ^ a b Jeyaprakash K, Chinnaswamy P. Hypocholesterolaemic effect of spirulina and liv-52 in lead induced toxicity in albino rats. Anc Sci Life. (2004)
  61. ^ a b Misbahuddin M, et al. Efficacy of spirulina extract plus zinc in patients of chronic arsenic poisoning: a randomized placebo-controlled study. Clin Toxicol (Phila). (2006)
  62. ^ a b c Savranoglub S, Tumer TB. Inhibitory Effects of Spirulina platensis on Carcinogen-Activating Cytochrome P450 Isozymes and Potential for Drug Interactions. Int J Toxicol. (2013)
  63. ^ a b c Nishanth RP, et al. C-Phycocyanin inhibits MDR1 through reactive oxygen species and cyclooxygenase-2 mediated pathways in human hepatocellular carcinoma cell line. Eur J Pharmacol. (2010)
  64. ^ Roy KR, et al. C-Phycocyanin ameliorates 2-acetylaminofluorene induced oxidative stress and MDR1 expression in the liver of albino mice. Hepatol Res. (2008)
  65. ^ Roy KR, et al. C-Phycocyanin inhibits 2-acetylaminofluorene-induced expression of MDR1 in mouse macrophage cells: ROS mediated pathway determined via combination of experimental and In silico analysis. Arch Biochem Biophys. (2007)
  66. ^ Khan M, et al. C-phycocyanin ameliorates doxorubicin-induced oxidative stress and apoptosis in adult rat cardiomyocytes. J Cardiovasc Pharmacol. (2006)
  67. ^ Terry MJ, Maines MD, Lagarias JC. Inactivation of phytochrome- and phycobiliprotein-chromophore precursors by rat liver biliverdin reductase. J Biol Chem. (1993)
  68. ^ Riss J, et al. Phycobiliprotein C-phycocyanin from Spirulina platensis is powerfully responsible for reducing oxidative stress and NADPH oxidase expression induced by an atherogenic diet in hamsters. J Agric Food Chem. (2007)
  69. ^ a b c d e Pabon MM, et al. A Spirulina-Enhanced Diet Provides Neuroprotection in an α-Synuclein Model of Parkinson's Disease. PLoS One. (2012)
  70. ^ Cardona AE, et al. Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci. (2006)
  71. ^ a b CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson's disease.
  72. ^ Rimbau V, et al. Protective effects of C-phycocyanin against kainic acid-induced neuronal damage in rat hippocampus. Neurosci Lett. (1999)
  73. ^ Patel M, et al. Activation of NADPH oxidase and extracellular superoxide production in seizure-induced hippocampal damage. J Neurochem. (2005)
  74. ^ Lanone S, et al. Bilirubin decreases nos2 expression via inhibition of NAD(P)H oxidase: implications for protection against endotoxic shock in rats. FASEB J. (2005)
  75. ^ Chamorro G, et al. Spirulina maxima pretreatment partially protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. Nutr Neurosci. (2006)
  76. ^ Strömberg I, et al. Blueberry- and spirulina-enriched diets enhance striatal dopamine recovery and induce a rapid, transient microglia activation after injury of the rat nigrostriatal dopamine system. Exp Neurol. (2005)
  77. ^ Wu DC, et al. NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. Proc Natl Acad Sci U S A. (2003)
  78. ^ Tieu K, Ischiropoulos H, Przedborski S. Nitric oxide and reactive oxygen species in Parkinson's disease. IUBMB Life. (2003)
  79. ^ Zhang W, et al. Neuroprotective effect of dextromethorphan in the MPTP Parkinson's disease model: role of NADPH oxidase. FASEB J. (2004)
  80. ^ Choi DH, et al. NADPH oxidase 1-mediated oxidative stress leads to dopamine neuron death in Parkinson's disease. Antioxid Redox Signal. (2012)
  81. ^ Thaakur SR, Jyothi B. Effect of spirulina maxima on the haloperidol induced tardive dyskinesia and oxidative stress in rats. J Neural Transm. (2007)
  82. ^ Subramanyam B, et al. Identification of a potentially neurotoxic pyridinium metabolite of haloperidol in rats. Biochem Biophys Res Commun. (1990)
  83. ^ Eyles DW, McGrath JJ, Pond SM. Formation of pyridinium species of haloperidol in human liver and brain. Psychopharmacology (Berl). (1996)
  84. ^ Thaakur S, Sravanthi R. Neuroprotective effect of Spirulina in cerebral ischemia-reperfusion injury in rats. J Neural Transm. (2010)
  85. ^ Wang Y, et al. Dietary supplementation with blueberries, spinach, or spirulina reduces ischemic brain damage. Exp Neurol. (2005)
  86. ^ Pentón-Rol G, et al. C-Phycocyanin is neuroprotective against global cerebral ischemia/reperfusion injury in gerbils. Brain Res Bull. (2011)
  87. ^ a b Bermejo-Bescós P, Piñero-Estrada E, Villar del Fresno AM. Neuroprotection by Spirulina platensis protean extract and phycocyanin against iron-induced toxicity in SH-SY5Y neuroblastoma cells. Toxicol In Vitro. (2008)
  88. ^ George S, et al. α-Synuclein: The Long Distance Runner. Brain Pathol. (2013)
  89. ^ Lehéricy S, et al. Magnetic resonance imaging of the substantia nigra in Parkinson's disease. Mov Disord. (2012)
  90. ^ Surmeier DJ, et al. The role of calcium and mitochondrial oxidant stress in the loss of substantia nigra pars compacta dopaminergic neurons in Parkinson's disease. Neuroscience. (2011)
  91. ^ a b Guo JP, Yu S, McGeer PL. Simple in vitro assays to identify amyloid-beta aggregation blockers for Alzheimer's disease therapy. J Alzheimers Dis. (2010)
  92. ^ a b Hwang JH, et al. Spirulina prevents memory dysfunction, reduces oxidative stress damage and augments antioxidant activity in senescence-accelerated mice. J Nutr Sci Vitaminol (Tokyo). (2011)
  93. ^ Alpha-synuclein release by neurons activates the inflammatory response in a microglial cell line.
  94. ^ Zhang QG, et al. Critical role of NADPH oxidase in neuronal oxidative damage and microglia activation following traumatic brain injury. PLoS One. (2012)
  95. ^ Chen JC, et al. Spirulina and C-phycocyanin reduce cytotoxicity and inflammation-related genes expression of microglial cells. Nutr Neurosci. (2012)
  96. ^ a b c Patro N, et al. Spirulina platensis protects neurons via suppression of glial activation and peripheral sensitization leading to restoration of motor function in collagen-induced arthritic rats. Indian J Exp Biol. (2011)
  97. ^ Gemma C, et al. Diets enriched in foods with high antioxidant activity reverse age-induced decreases in cerebellar beta-adrenergic function and increases in proinflammatory cytokines. J Neurosci. (2002)
  98. ^ a b c d Spirulina Promotes Stem Cell Genesis and Protects against LPS Induced Declines in Neural Stem Cell Proliferation.
  99. ^ Short Communication: Neuroprotective Effect of Spirulina in a Mouse Model of ALS.
  100. ^ ALSUntangled Group. ALSUntangled No. 9: Blue-green algae (Spirulina) as a treatment for ALS. Amyotroph Lateral Scler. (2011)
  101. ^ a b Kim NH, et al. The effect of hydrolyzed Spirulina by malted barley on forced swimming test in ICR mice. Int J Neurosci. (2008)
  102. ^ a b c d Huang H, et al. Quantifying the effects of spirulina supplementation on plasma lipid and glucose concentrations, body weight, and blood pressure. Diabetes Metab Syndr Obes. (2018)
  103. ^ Carrizzo A, et al. Novel Potent Decameric Peptide of Spirulina platensis Reduces Blood Pressure Levels Through a PI3K/AKT/eNOS-Dependent Mechanism. Hypertension. (2019)
  104. ^ Juárez-Oropeza MA, et al. Effects of dietary Spirulina on vascular reactivity. J Med Food. (2009)
  105. ^ Brito AF, et al. Aortic Response to Strength Training and Spirulina platensis Dependent on Nitric Oxide and Antioxidants. Front Physiol. (2018)
  106. ^ Hsiao G, et al. C-phycocyanin, a very potent and novel platelet aggregation inhibitor from Spirulina platensis. J Agric Food Chem. (2005)
  107. ^ a b Torres-Durán PV, et al. Effect of Spirulina maxima on postprandial lipemia in young runners: a preliminary report. J Med Food. (2012)
  108. ^ Nagaoka S, et al. A novel protein C-phycocyanin plays a crucial role in the hypocholesterolemic action of Spirulina platensis concentrate in rats. J Nutr. (2005)
  109. ^ Serban MC, et al. A systematic review and meta-analysis of the impact of Spirulina supplementation on plasma lipid concentrations. Clin Nutr. (2016)
  110. ^ Szulinska M, et al. Spirulina maxima improves insulin sensitivity, lipid profile, and total antioxidant status in obese patients with well-treated hypertension: a randomized double-blind placebo-controlled study. Eur Rev Med Pharmacol Sci. (2017)
  111. ^ a b Marcel AK, et al. The effect of Spirulina platensis versus soybean on insulin resistance in HIV-infected patients: a randomized pilot study. Nutrients. (2011)
  112. ^ Vigouroux C, et al. Adverse metabolic disorders during highly active antiretroviral treatments (HAART) of HIV disease. Diabetes Metab. (1999)
  113. ^ 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)
  114. ^ Kaur K, Sachdeva R, Grover K. Effect of supplementation of spirulina on blood glucose and lipid profile of the non-insulin dependent diabetic male subjects. Asian Journal of Dairy and Food Research. (2008)
  115. ^ Lee EH, et al. A randomized study to establish the effects of spirulina in type 2 diabetes mellitus patients. Nutr Res Pract. (2008)
  116. ^ a b c d e Fujimoto M, et al. Spirulina improves non-alcoholic steatohepatitis, visceral fat macrophage aggregation, and serum leptin in a mouse model of metabolic syndrome. Dig Liver Dis. (2012)
  117. ^ Obesity is associated with macrophage accumulation in adipose tissue.
  118. ^ a b Furukawa S, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. (2004)
  119. ^ Iwatsuka H, Shino A, Suzuoki Z. General survey of diabetic features of yellow KK mice. Endocrinol Jpn. (1970)
  120. ^ Ou Y, et al. Antidiabetic potential of phycocyanin: Effects on KKAy mice. Pharm Biol. (2013)
  121. ^ a b c d Nielsen CH, et al. Enhancement of natural killer cell activity in healthy subjects by Immulina®, a Spirulina extract enriched for Braun-type lipoproteins. Planta Med. (2010)
  122. ^ Lipoprotein is a predominant Toll-like receptor 2 ligand in Staphylococcus aureus cell wall components.
  123. ^ Balachandran P, et al. Toll-like receptor 2-dependent activation of monocytes by Spirulina polysaccharide and its immune enhancing action in mice. Int Immunopharmacol. (2006)
  124. ^ Ku CS, et al. Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes. Biochim Biophys Acta. (2013)
  125. ^ SCN Signs Major World-Wide Distribution Agreement for Patented Immune Product.
  126. ^ Grzanna R, et al. Immolina, a high-molecular-weight polysaccharide fraction of Spirulina, enhances chemokine expression in human monocytic THP-1 cells. J Altern Complement Med. (2006)
  127. ^ a b DuBois RN, et al. Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors. Gastroenterology. (1996)
  128. ^ a b c d Saini MK, Sanyal SN. PTEN regulates apoptotic cell death through PI3-K/Akt/GSK3β signaling pathway in DMH induced early colon carcinogenesis in rat. Exp Mol Pathol. (2012)
  129. ^ Reddy MC, et al. C-Phycocyanin, a selective cyclooxygenase-2 inhibitor, induces apoptosis in lipopolysaccharide-stimulated RAW 264.7 macrophages. Biochem Biophys Res Commun. (2003)
  130. ^ a b c d Reddy CM, et al. Selective inhibition of cyclooxygenase-2 by C-phycocyanin, a biliprotein from Spirulina platensis. Biochem Biophys Res Commun. (2000)
  131. ^ Shih CM, et al. Antiinflammatory and antihyperalgesic activity of C-phycocyanin. Anesth Analg. (2009)
  132. ^ Nemoto-Kawamura C, et al. Phycocyanin enhances secretary IgA antibody response and suppresses allergic IgE antibody response in mice immunized with antigen-entrapped biodegradable microparticles. J Nutr Sci Vitaminol (Tokyo). (2004)
  133. ^ a b Hirahashi T, et al. Activation of the human innate immune system by Spirulina: augmentation of interferon production and NK cytotoxicity by oral administration of hot water extract of Spirulina platensis. Int Immunopharmacol. (2002)
  134. ^ a b c d e Akao Y, et al. Enhancement of antitumor natural killer cell activation by orally administered Spirulina extract in mice. Cancer Sci. (2009)
  135. ^ Akazawa T, et al. Antitumor NK activation induced by the Toll-like receptor 3-TICAM-1 (TRIF) pathway in myeloid dendritic cells. Proc Natl Acad Sci U S A. (2007)
  136. ^ a b c Pak W, et al. Anti-oxidative and anti-inflammatory effects of spirulina on rat model of non-alcoholic steatohepatitis. J Clin Biochem Nutr. (2012)
  137. ^ a b Joventino IP, et al. The microalga Spirulina platensis presents anti-inflammatory action as well as hypoglycemic and hypolipidemic properties in diabetic rats. J Complement Integr Med. (2012)
  138. ^ a b Kumar N, et al. Evaluation of protective efficacy of Spirulina platensis against collagen-induced arthritis in rats. Inflammopharmacology. (2009)
  139. ^ a b Rasool M, Sabina EP, Lavanya B. Anti-inflammatory effect of Spirulina fusiformis on adjuvant-induced arthritis in mice. Biol Pharm Bull. (2006)
  140. ^ a b Remirez D, et al. Inhibitory effects of Spirulina in zymosan-induced arthritis in mice. Mediators Inflamm. (2002)
  141. ^ a b Cingi C, et al. The effects of spirulina on allergic rhinitis. Eur Arch Otorhinolaryngol. (2008)
  142. ^ Mao TK, Van de Water J, Gershwin ME. Effects of a Spirulina-based dietary supplement on cytokine production from allergic rhinitis patients. J Med Food. (2005)
  143. ^ a b Park HJ, et al. A randomized double-blind, placebo-controlled study to establish the effects of spirulina in elderly Koreans. Ann Nutr Metab. (2008)
  144. ^ a b Chu WL, et al. Protective effect of aqueous extract from Spirulina platensis against cell death induced by free radicals. BMC Complement Altern Med. (2010)
  145. ^ a b Shyam R, et al. Wheat grass supplementation decreases oxidative stress in healthy subjects: a comparative study with spirulina. J Altern Complement Med. (2007)
  146. ^ a b Chamorro-Cevallos G, et al. Chemoprotective effect of Spirulina (Arthrospira) against cyclophosphamide-induced mutagenicity in mice. Food Chem Toxicol. (2008)
  147. ^ a b c Hassan AM, Abdel-Aziem SH, Abdel-Wahhab MA. Modulation of DNA damage and alteration of gene expression during aflatoxicosis via dietary supplementation of Spirulina (Arthrospira) and Whey protein concentrate. Ecotoxicol Environ Saf. (2012)
  148. ^ Deryagina VP, Ryzhova NI, Golubkina NA. Production of nitrogen oxide derivatives under the influence of NO-synthase inhibitors and natural compounds in mice with transplanted tumors. Exp Oncol. (2012)
  149. ^ Mathew B, et al. Evaluation of chemoprevention of oral cancer with Spirulina fusiformis. Nutr Cancer. (1995)
  150. ^ Mishima T, et al. Inhibition of tumor invasion and metastasis by calcium spirulan (Ca-SP), a novel sulfated polysaccharide derived from a blue-green alga, Spirulina platensis. Clin Exp Metastasis. (1998)
  151. ^ McCarty MF. Minimizing the cancer-promotional activity of cox-2 as a central strategy in cancer prevention. Med Hypotheses. (2012)
  152. ^ a b Saini MK, Sanyal SN, Vaiphei K. Piroxicam and C-phycocyanin mediated apoptosis in 1,2-dimethylhydrazine dihydrochloride induced colon carcinogenesis: exploring the mitochondrial pathway. Nutr Cancer. (2012)
  153. ^ a b c Saini MK, Vaiphei K, Sanyal SN. Chemoprevention of DMH-induced rat colon carcinoma initiation by combination administration of piroxicam and C-phycocyanin. Mol Cell Biochem. (2012)
  154. ^ a b Voltarelli FA, de Mello MA. Spirulina enhanced the skeletal muscle protein in growing rats. Eur J Nutr. (2008)
  155. ^ Efficacy of Spirulina Supplementation on Isometric Strength and Isometric Endurance of Quadriceps in Trained and Untrained Individuals – a comparative study.
  156. ^ a b c Lu HK, et al. Preventive effects of Spirulina platensis on skeletal muscle damage under exercise-induced oxidative stress. Eur J Appl Physiol. (2006)
  157. ^ Kalafati M, et al. Ergogenic and antioxidant effects of spirulina supplementation in humans. Med Sci Sports Exerc. (2010)
  158. ^ Baicus C, Baicus A. Spirulina did not ameliorate idiopathic chronic fatigue in four N-of-1 randomized controlled trials. Phytother Res. (2007)
  159. ^ Ishimi Y, et al. Effects of spirulina, a blue-green alga, on bone metabolism in ovariectomized rats and hindlimb-unloaded mice. Biosci Biotechnol Biochem. (2006)
  160. ^ a b Bhattacharyya S, Mehta P. The hepatoprotective potential of Spirulina and vitamin C supplemention in cisplatin toxicity. Food Funct. (2012)
  161. ^ Lu J, et al. Protection by dietary Spirulina platensis against D-galactosamine--and acetaminophen-induced liver injuries. Br J Nutr. (2010)
  162. ^ a b Jarouliya U, et al. Alleviation of metabolic abnormalities induced by excessive fructose administration in Wistar rats by Spirulina maxima. Indian J Med Res. (2012)
  163. ^ Effect of Supplementation of Spirulina on Hypercholesterolemic Patients.
  164. ^ McCarty MF, Barroso-Aranda J, Contreras F. Genistein and phycocyanobilin may prevent hepatic fibrosis by suppressing proliferation and activation of hepatic stellate cells. Med Hypotheses. (2009)
  165. ^ Liu XJ, et al. Effects of the tyrosine protein kinase inhibitor genistein on the proliferation, activation of cultured rat hepatic stellate cells. World J Gastroenterol. (2002)
  166. ^ Itagaki T, et al. Opposing effects of oestradiol and progesterone on intracellular pathways and activation processes in the oxidative stress induced activation of cultured rat hepatic stellate cells. Gut. (2005)
  167. ^ Bataller R, et al. NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. J Clin Invest. (2003)
  168. ^ Adachi T, et al. NAD(P)H oxidase plays a crucial role in PDGF-induced proliferation of hepatic stellate cells. Hepatology. (2005)
  169. ^ Nakanishi Y, et al. Monosodium glutamate (MSG): a villain and promoter of liver inflammation and dysplasia. J Autoimmun. (2008)
  170. ^ Moura LP, et al. Exercise and spirulina control non-alcoholic hepatic steatosis and lipid profile in diabetic Wistar rats. Lipids Health Dis. (2011)
  171. ^ Blé-Castillo JL, et al. Arthrospira maxima prevents the acute fatty liver induced by the administration of simvastatin, ethanol and a hypercholesterolemic diet to mice. Life Sci. (2002)
  172. ^ a b Ferreira-Hermosillo A, Torres-Duran PV, Juarez-Oropeza MA. Hepatoprotective effects of Spirulina maxima in patients with non-alcoholic fatty liver disease: a case series. J Med Case Rep. (2010)
  173. ^ Hernández-Corona A, et al. Antiviral activity of Spirulina maxima against herpes simplex virus type 2. Antiviral Res. (2002)
  174. ^ a b Yakoot M, Salem A. Spirulina platensis versus silymarin in the treatment of chronic hepatitis C virus infection. A pilot randomized, comparative clinical trial. BMC Gastroenterol. (2012)
  175. ^ Băicuş C, Tănăsescu C. Chronic viral hepatitis, the treatment with spiruline for one month has no effect on the aminotransferases. Rom J Intern Med. (2002)
  176. ^ Teas J, Irhimeh MR. Dietary algae and HIV/AIDS: proof of concept clinical data. J Appl Phycol. (2012)
  177. ^ a b Selmi C, et al. The effects of Spirulina on anemia and immune function in senior citizens. Cell Mol Immunol. (2011)
  178. ^ a b Gupta M, Dwivedi UN, Khandelwal S. C-Phycocyanin: an effective protective agent against thymic atrophy by tributyltin. Toxicol Lett. (2011)
  179. ^ Rodríguez-Sánchez R, et al. Phycobiliproteins or C-phycocyanin of Arthrospira (Spirulina) maxima protect against HgCl(2)-caused oxidative stress and renal damage. Food Chem. (2012)
  180. ^ Mohan IK, et al. Protection against cisplatin-induced nephrotoxicity by Spirulina in rats. Cancer Chemother Pharmacol. (2006)
  181. ^ Lim BJ, et al. C-phycocyanin attenuates cisplatin-induced nephrotoxicity in mice. Ren Fail. (2012)
  182. ^ Sinanoglu O, et al. The Protective Effects of Spirulina in Cyclophosphamide Induced Nephrotoxicity and Urotoxicity in Rats. Urology. (2012)
  183. ^ Viswanadha VP, Sivan S, Rajendra Shenoi R. Protective effect of Spirulina against 4-nitroquinoline-1-oxide induced toxicity. Mol Biol Rep. (2011)
  184. ^ Avdagić N, et al. Spirulina platensis protects against renal injury in rats with gentamicin-induced acute tubular necrosis. Bosn J Basic Med Sci. (2008)
  185. ^ Kim DH, et al. Molecular Study of Dietary Heptadecane for the Anti-Inflammatory Modulation of NF-kB in the Aged Kidney. PLoS One. (2013)
  186. ^ Sun YX, et al. Experimental study on the therapeutic effect of C-phycocyanin against pulmonary fibrosis induced by paraquat in rats. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. (2012)
  187. ^ a b c Bickford PC, et al. Nutraceuticals synergistically promote proliferation of human stem cells. Stem Cells Dev. (2006)
  188. ^ Acosta S, et al. NT-020, a natural therapeutic approach to optimize spatial memory performance and increase neural progenitor cell proliferation and decrease inflammation in the aged rat. Rejuvenation Res. (2010)
  189. ^ Yasuhara T, et al. Dietary supplementation exerts neuroprotective effects in ischemic stroke model. Rejuvenation Res. (2008)
  190. ^ Shytle RD, et al. Oxidative stress of neural, hematopoietic, and stem cells: protection by natural compounds. Rejuvenation Res. (2007)
  191. Torres-Duran PV, Ferreira-Hermosillo A, Juarez-Oropeza MA. Antihyperlipemic and antihypertensive effects of Spirulina maxima in an open sample of Mexican population: a preliminary report. Lipids Health Dis. (2007)
  192. Mazokopakis EE, et al. The hypolipidemic effects of Spirulina (Arthrospira platensis) supplementation in a Cretan population: a prospective study. J Sci Food Agric. (2013)
  193. Ashraf R, et al. Effects of Allium sativum (Garlic) on systolic and diastolic blood pressure in patients with essential hypertension. Pak J Pharm Sci. (2013)
  194. Ried K, Toben C, Fakler P. Effect of garlic on serum lipids: an updated meta-analysis. Nutr Rev. (2013)
  195. Hou LQ, Liu YH, Zhang YY. Garlic intake lowers fasting blood glucose: meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr. (2015)
  196. Bowtell JL, et al. Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation. Appl Physiol Nutr Metab. (2017)
  197. Krikorian R, et al. Blueberry supplementation improves memory in older adults. J Agric Food Chem. (2010)
  198. Rendeiro C, et al. Blueberry supplementation induces spatial memory improvements and region-specific regulation of hippocampal BDNF mRNA expression in young rats. Psychopharmacology (Berl). (2012)
  199. Whyte AR, Schafer G, Williams CM. Cognitive effects following acute wild blueberry supplementation in 7- to 10-year-old children. Eur J Nutr. (2016)
  200. Potential health benefits of spirulina microalgae.
  201. Characterization of Spirulina Biomass for CELSS Diet Potential.
  202. Vitamin A.
  203. Wu Q, et al. The antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina: an overview. Arch Toxicol. (2016)
  204. Kerley CP. Dietary nitrate as modulator of physical performance and cardiovascular health. Curr Opin Clin Nutr Metab Care. (2017)
  205. Siervo M, et al. Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis. J Nutr. (2013)