Thus, multiple studies on whole blue-green-algae in humans, mice, rats, cats, and chickens have demonstrated an effect on phagocytosis, NK cell function, and inflamma­tion. Some differences exist in the data, including the mild reduction of phagocytic activity in humans after algae con­sumption, in contrast to the increase of phagocytosis among bronchoalveolar macrophages. The cell types and experimental set-ups vary, and further studies are needed to estab­lish the exact biochemical mechanisms involved.

Hayashi et al7 examined the effect of an algae-supple-mented diet on the ability to build a specific immune response

Table 2. Immuno-Modulatory and Anti-Inflammatory Effects of Whole Blue-Green Algae

Algae Species

Introduced as:

Test Species

Effects Reference
Spirulina sp. Food Human Reversal of tobacco-induced oral cancer Mathew et al, 1995
Food Mouse Proportional reduction of IgE, increase of IgA Hayashi et al, 1998
Food Mouse Increased phagocytic activity Increased spleen cell proliferation Increased antibody production Hayashi et al, 1994
Food Chicken Increased phagocytic activity Increased NK cell-mediated anti-tumor activity Increased antibody production Qureshi et al, 1996

In vitro, cat

Increased phagocytic activity

Qureshi & Ali, 1996

IP injection Rat Inhibition of mast cells Decrease in local allergic reaction Decrease in serum histamine levels Reduced allergy-induced mortality Kim et al, 1998 Yang et al, 1997
Aphanizomenon flos-aquae Food Human Increased transient recruitment of NK cells into tissue Increased mobilization of T and B cells into blood Mild modulation of PMN-mediated phagocytic response Jensen et al, 2000
Food Rat Decreased serum levels of arachidonic acid Kushak et al, 2000
Food Rat Source of linolenic acid (omega-3) Increased serum levels of EPA and DHA Kushak et al, 2000

In vitro, rat

Activation of macrophages (NF-kappaB, cytokines) Pasco, in press

to sheep red blood cells. After immunizing mice (either once to measure the primary response or twice for the secondary response), they found that mice fed with the algae-supple-mented diet showed increased numbers of splenic IgM anti-body-producing cells when compared to control animals. Interestingly, this finding only held true for the primary immune response, as the IgG antibody production in the sec­ondary immune response was hardly affected. In experiments involving chickens, there were no differences observed in anti-sheep red blood cell antibodies during primary responses, while antibody titers for the secondary response in algae-fed chickens were augmented compared to control animals.8 The differences may reflect the anatomical differences between the rodent and chicken immune systems.

Hayashi et al10 examined other antibody classes such as IgA and IgE in the context of mice orally immunized with a crude shrimp extract. They found that whereby both IgA (intestinal) and IgE (in serum) levels increased with antigen challenge, only IgA levels showed a greater enhancement in secretion with concurrent treatment with Spirulina extract (five-week feeding regimen).10 From this study they con­cluded that bluegreen algae does not seem to induce or enhance food allergic IgE-dependent reactions.  Furthermore, they suggest that when ingested along with or before a poten­tial antigenic threat, bluegreen algae may enhance IgA anti- body levels to protect against food allergies.

Along the same lines, further studies have suggested that blue-green algae may inhibit mast cell-mediated type I aller­gic reactions and even the anaphylactic reaction in rats.11,12 By injecting a blue-green algae extract intraperitoneally (100-1000mg/g body weight) one hour prior to an allergic challenge, mortality induced by the anaphylactic compound 48/80 was decreased, local allergic reaction activated by anti­dinitrophenyl (anti-DNP) IgE was inhibited, and serum hist­amine levels were decreased. In vitro experiments from this group provided similar results.

The effects of blue-green-algae on IgE-production and allergic reactions are encouraging, and warrant further studies in humans.

Much attention with regards to dietary modulation of the immune system has been given to stimulating activity of various immune cell types such as the phagocytic activity of macrophages, or the tumoricidal activity of natural killer cells. However, immune cell trafficking and the recruitment of immune cells from the systemic circulation are of equal importance. A recent study by Jensen et al5 involving

Table 3. Bio-modulatory Effects of Purified Compounds from Blue-Green Algae

Species Compound Effects References
All blue-green algae C-Phycocyanin Anti-inflammatory (reduces leukotriene B4) Free radical scavenger Selective inhibition of COX-2 Reduced tissue damage in acetic acid-induced colitis Hepatoprotective effect Romay 1999 Bhat & Madyastha 2000 Reddy et al, 2000 Gonzalez et al, 1999 Vadiraja et al, 1998
Spirulina Calcium Spirulan (Ca-Sp) Selectively inhibits penetration of virus into host cell (Herpex Simplex, human cytomegalovirus, measles, mumps, Influenza A, HIV-1) Hayashi et al, 1996
Reduces lung metastasis of melanoma cells by inhibition of tumor cell invasion of basal membrane Mishima et al, 1998
Cyanovirin-N Irreversible inactivation of several strains of HIV (inhibited cell-to-cell and virus-to-cell fusion) Boyd, 1997

Extracellular products

Promotion of lactic acid bacteria growth in vitro Parada et al, 1998
Aphanizomenon flos aquae Unknown Polysaccharide Induces apoptosis in some human tumor cell lines Stimulate the macrophage activity Jensen, msp in prep Pasco et al, in press.
Lyngbya lagerheimii Phormidium tenue Sulfolipid Inhibits syncytium formation upon HIV infection Gustafson et al, 1989
Phormidium tenue

Digalactosyl diacylglycerols

Inhibition of chemically induced skin tumors Tokuda et al, 1996

humans demonstrated that the blue-green alga Aphanizomenon flos-aquae was able to trigger within two hours the migra­tion of nearly 40% of the circulating natural killer cells. This effect was significantly more pronounced in long-term consumers than in naïve subjects. In the same study, Aphanizomenon flos-aquae was also shown to stimulate the mobilization of T and B lymphocytes. This effect appeared cell-type specific since no changes were observed on poly­morph nucleated cells.

Blue-green algae in general contain a significant amount of carotenoids, namely beta carotene, lycopene, and lutein, providing it with good antioxidant properties. By their quenching action on reactive oxygen species, antioxi­dants carry intrinsic anti-inflammatory properties. However, blue green algae also contains specific anti­inflammatory properties as a result of their high phyco­cyanin content. Phycocyanin is a photoharvesting pigment that provides the intense blue color in blue green algae. It can constitute up to 15% of the dry weight of a blue green algae harvest. C-phycocyanin is a free radical scavenger,26 and has significant hepatoprotective effects.27 Phycocyanin was shown to inhibit inflammation in mouse ears28 and pre-tory effect seemed to be a result of phycocyanin to inhibit the formation of leukotriene B4, an inflammatory metabo­lite of arachidonic acid.28

In a study performed in rats, the blue-green algae Aphanizomenon flos-aquae was also shown to decrease the plasma level of arachidonic acid.30 Aphanizomenon flos­aquae contains significant amounts of the omega-3 alpha-linolenic acid. Omega-3 fatty acids have been shown to inhibit the formation of inflammatory prostaglandins and arachidonate metabolites. Since Spirulina contains signifi­cant amounts of omega-6 gamma-linolenic acid, the anti­inflammatory properties of Spirulina must be due to differ­ent biochemical pathways.

As part of its program aimed at discovering new anti­tumor and anti-viral agents in natural sources, the National Cancer Institute isolated extracts of blue-green algae (Lyngbya lagerheimii and Phormidium tenue) that were found to protect human lymphoblastoid T cells from the cytopathic effect of HIV infection.  Upon further investigation, a new class of HIV inhibitory compounds called the sulfonic acid-containing glycolipids were isolated; the pure compounds were found to be strikingly active against the HIV virus in the p24 viral protein and syncytium formation assays.13 Since this discovery, there has been further investigation into other species of blue-green algae for compounds with anti-viral properties. Some compounds worthy of mention include a protein called cyanovirin-N which appears to irreversibly inactivate diverse strains of the HIV virus and to inhibit cell-to-cell and virus-to-cell fusion.14 Other studies using a water-soluble extract of blue-green algae have found a novel sulfat­ed polysaccharide, calcium spirulan (Ca-SP), to be an antivi­ral agent. This compound appears to selectively inhibit the penetration of enveloped viruses (Herpes simplex, human cytomegalovirus, measles virus, mumps virus, influenza A virus, and HIV-1) into host cells, thereby preventing replica-tion.15-17 A review of anti-HIV activity of extracts from blue-green algae has been recently published.18

An early study on bluegreen algae’s cancer-preventive properties in humans was performed on tobacco-induced oral leukoplakia.19 Mathew et al found that oral supplemen­tation with Spirulina fusiformis resulted in complete regres­sion of 57% of subjects with homogenous leukoplakia. After discontinuation of Spirulina supplementation, almost half of the complete responders developed recurrent lesions.

In other studies, extracts of bluegreen algae have been used to treat cancer in animal models. In one model, inges­tion of an extract of Spirulina and Dunaliella was shown to inhibit chemically-induced carcinogenesis in hamster buc­cal pouches.20,21 Earlier studies often attributed the anti­cancer effect of algae to its content in carotenoids since beta-carotene has been shown to have an effect similar to that of algae extract. A more recent study, however, showed that the sulfated polysaccharide mentioned above, Ca-SP, appears to inhibit tumor invasion and metastasis.22 Both the in vitro and in vivo effects of Ca-SP suggest that the intra­venous administration of Ca-SP reduces the lung metastasis of melanoma cells by inhibiting the tumor invasion of the basement membrane. A water-based extract of Aphanizomenon flos aquae containing high concentrations of phycocyanin inhibited the in vitro growth of one out of four tumor cell lines tested, indicating that at least some tumor cell types may be directly sensitive to killing by phycocyanin (Jensen et al, manuscript in preparation). Another fresh-water blue-green algae, Phormidium tenue, contains several diacyl­glycerol compounds which effectively inhibited chemical-ly-induced skin tumors in mice.23 In addition, Spirulina was shown to have a modulatory effect on hepatic carcinogen metabolizing enzymes.24

Of major interest to ongoing research in inflammation as well as breast cancer is the finding that C-phycocyanin selectively inhibits COX-2, but has no effect on COX-1.25 The COX enzymes are involved in prostaglandin synthesis. Since COX-2 is over-expressed in many breast cancer cells, and inhibition of COX-2 leads to a markedly reduced tumor growth and blocks angiogenesis, the finding that phyco­cyanin specifically interferes with this pathway holds promise.

Besides their effects on the immune system, blue-green algae have also been reported to modulate other systems and improve metabolism. In the past few years increasing attention has been given to the study of the therapeutic effects of blue-green algae. The anecdotal claims for such effects are numer­ous. Although there is limited data from controlled animal or clinical studies, such claims include improvement in condition of Alzheimer’s patients, overall enhancement of immune response, improvement in fibromyalgia, control of hyperten­sion, alleviation of depression and chronic fatigue, increased stamina, healing of internal and external lesions, increased mental acuity, and general improvement in overall well-being. This last section will review the scientific evidence supporting the therapeutic effects of blue-green algae.

Several reports from different labs have shown that cer­tain species of blue-green algae have cholesterol-lowering effects in animal and human models.  In feeding experiments in rats, two studies have reported that the elevation in total cholesterol, LDL, and VLDL cholesterol in serum caused by cholesterol feeding was reduced when the high cholesterol diet was supplemented with 16% and 5% blue-green algae, respectively.31,32 In addition, Kato found that adipohepatosis induced by a high fat and high cholesterol diet was cured rapidly when the diet was supplemented with algae.31 Investigations into the mechanism of this phenomenon led to the finding that the algae-fed group showed a statistically sig­nificant increase in the activity of lipoprotein lipase, a key enzyme in the metabolism of triglyceride-rich lipoproteins.33

The hypocholesterolemic effect of blue green algae was also observed in humans in a study conducted on 30 patients with mild hyperlipidemia and mild hypertension.34 Patients took 4.2 grams of algae or placebo per day, and were observed for two months. At the end of the study, patients taking the algae showed a significant reduction of LDL-cho-lesterol (p<0.05) compared to the control group. LDL cho­lesterol increased back to baseline levels after administration of the algae was discontinued. In addition to lowering LDL cholesterol levels, the atherogenic index (a measure of fat deposition in arteries) declined significantly after four weeks of algae consumption.

In a recent study by Kushak et al, rats were fed the blue-green alga Aphanizomenon flos-aquae and total cholesterol level was monitored. After 43 days, cholesterol levels were significantly decreased when compared to the control group.30 Although Aphanizomenon flos-aquae contains a significant amount of the omega-3 polyunsaturated linolenic

Table 4. Biomodulatory Effects of Whole Blue-Green Algae on Metabolism

Algae Species Introduced as

Test Species

Effects Reference Effects
Aphanizomenon Food Rat Reduction of cholesterol Kushak et al, 2000 Reduction of cholesterol
Food Rat Reduction of blood glucose levels Drapeau et al, 2001 Reduction of blood glucose levels
Food Human Modulation of brain activity (EEG) Walker & Valencia, 1999 Modulation of brain activity (EEG)
Spirulina Food Human Reduced body weight Becker et al, 1986 Reduced body weight
Food Rat Reduction of cholesterol Kato et al, 1984 Reduction of cholesterol
Food Rat Increased activity of lipase Iwata et al, 1990 Increased activity of lipase
Food Rat Reduced glucose levels Takai et al, 1991 Reduced glucose levels
Food Rat Inhibition of maltase and sucrase Kushak et al, 1999 Inhibition of maltase and sucrase
Food Mouse Modulation of carcinogen metabolic enzymes Mittal et al, 1999 Modulation of carcinogen metabolic enzymes
Food Mouse Modulation of lead toxicity Shastri et al, 1999 Modulation of lead toxicity
Food Rat

Increased iron status during pregnancy and lactation

Kapoor & Mehta, 1998

Increased iron status during pregnancy and lactation

Nostoc Food Rat Reduction of cholesterol Hori et al, 1994 Reduction of cholesterol

acid, the effect on cholesterol levels seemed unrelated to the lipid content of the diets. Kushak et al30 proposed that the hypocholesterolemic effect of Aphanizomenon flos-aquae may be due to its chlorophyll content which was shown to stimulate liver function and decrease blood cholesterol.35

In a double-blind crossover study involving human patients, supplementing the diets of obese outpatients with 2.8 grams of bluegreen algae three times daily over a four week period resulted in a statistically significant reduction of body weight.36 In a study measuring the effect of bluegreen algae on glucose levels in diabetic rats, the water-soluble fraction was found to be effective in lowering the serum glucose level at fasting, while the water insoluble fraction suppressed glu­cose levels at glucose loading.37 In another study investigating the effect of the blue-green alga Aphanizomenon flos-aquae on rat intestinal mucosal digestive enzymes, it was observed that this alga specifically inhibited the activity of maltase and sucrase in a dose-dependent manner.38 Furthermore, this decrease in enzymatic activity was accompanied by a dose-dependent decrease in blood glucose.

The overall conclusion is that blue-green algae may have benefits on lipid and sugar metabolism, as well as liver function. Further human studies are needed to address the feasibility of using blue-green algae in conjunction with cholesterol-lowering medication.

Other research studies on blue green algae consumption deserve mention. Many reports exist in the literature on its antimicrobial effects.  The secretion of anti-microbial sub­stances is an important part of the competition for ecological niches in the natural environment. However, an interesting caveat exists. In one study, Spirulina was cultured in vitro, and the extracellular medium was shown to stimulate the growth of lactic acid bacteria.39 If the growth-promoting sub-stance(s) exist in sufficient amounts intracellularly, blue green algae may play a role in vivo by supporting friendly gut bacteria. This leads to other facets of health including gut health and nutrient absorption. On that note, consumption of Spirulina was shown to support the iron status and hemoglo­bin of rats during pregnancy and lactation.40 Spirulina fusiformis had a significant protective effect against lead-induced toxicity in rats.41 Finally, a report by Valencia et al has presented evidence that Aphanizomenon flos-aquae accelerates recovery from mild traumatic brain injury.42

Research results based on the numerous isolated com­pounds from blue green algae warrant the exploration of using whole algae as conjunctive therapy due to the possible synergistic effects of many phytochemicals within the whole algae. The emergence of composite algae supple­ments in contrast to single algae supplements may also yield further anti-inflammatory, immune-boosting, and metabolic benefits. A significant body of data suggests that blue green algae immunoenhancing properties could be useful in the adjunct treatment of various diseases involving 1) sup­pressed or exhausted immune system, and 2) inappropriate immune response including allergies, autoimmune diseases, and chronic inflammatory conditions. The data presented also suggests that blue green algae could be useful as an adjunct in the treatment of cancer and AIDS, and calls for the design of controlled human clinical studies.


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Winter 2001 Vol. 3, No. 4  JANA  28

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