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(Reprinted with permission from the Journal of the American Nutraceutical Association) Consumption of AFA Has Rapid Effects on the Circulation of and Function of Immune Cells in Humans. Research by Gitte S. Jensen, PhD, et al. Favorable Effects of Blue Green Algae on Rat Plasma Lipids. Research by Rafail Kuskak, PhD, et al. (www.ana-jana.org)
WHY AFA? (Aphanizomenon flos-aquae) Consumption of Aphanizomenon flos-aquae has Rapid Effects on the Circulation and Function of Immune Cells in Humans
Gitte S. Jensen, PhD,*1 Donald I. Ginsberg, 1 Patricia Huerta, 1 Monica Citton, 1 Christian Drapeau, MS2 1Department of Surgery, McGill University, Montreal, Quebec 2Research and Development, Cell Tech, Klamath Falls, Oregon
JANA vol. 2 (3): 50-58
ABSTRACT
Objective: To examine the short-term effects of consumption of a moderate amount (1.5 grams) of the blue green algae Aphanizomenon flos-aquae (AFA), on the immune system.
Methods: Using a crossover, placebo-controlled, randomized, double-blind design, 21 volunteers were studied, including 5 long-term AFA consumers.
Results: Consumption of a moderate amount (1.5 grams) of the blue-green algae Aphanizomenon flos-aquae results in rapid changes in immune cell trafficking. Two hours after AFA consumption, a generalized mobilization of lymphocytes and monocytes, but not polymorph nucleated cells, was observed. This included increases in CD3+, CD4+, and CD8+ T cell subsets and CD19+ B cells. In addition, the relative proportions and absolute numbers of natural killer (NK) cells were reduced after AFA consumption. No changes were observed in the relative proportions of naïve versus memory T cells, neither in the CD4 nor the CD8 fractions. A mild but significant reduction in phagocytic activity was observed for polymorph nucleated cells. When freshly purified lymphocytes were exposed to AFA extract in vitro, direct activation was not induced, as evaluated by tyrosine phosphorylation and proliferative activity.
Discussion: The changes in immune cell trafficking displayed a high degree of cell specificity. Long-term consumers responded stronger with respect to altered immune cell trafficking. In vitro, AFA did not induce a direct activation of lymphocytes. These data support a signaling pathway from gut to CNS to lymphoid tissue. The signals from CNS may be crucial for the rapid changes in the general distribution and specific recruitment we observed. Moderate anti-inflammatory modulation may account for the modification of phagocytic activity.
Conclusion: Consumption of AFA leads to rapid changes in immune cell trafficking, but not direct activation of lymphocytes. Thus, AFA increases the immune surveillance without directly stimulating the immune system.
Antioxidant properties of novel phycocyanin extract from the blue-green alga Aphanizomenon flos-aquae Life Sciences 75 (2004) 2353-2362
Aphanizomenon flos-aquae (AFA) is a fresh water unicellular blue-green alga (cyanophyra) rich in phycocyanin (PC), a photosynthetic pigment with antioxidant and anti-inflammatory properties.
The purpose of this study was to evaluate the ability of a novel natural extract from AFA enriched with PC to project normal human erythrocytes and plasma samples against oxidative damage in vitro. In red blood cells, oxidative hemolysis and lipid peroxidation induced by the aqueous peroxyl radical generator [2, 2'-Azobis (2-amidinopropane) dihydrochloride, AAPH] were significantly lowered by the AFA extract in a time- and dose-dependent manner; at the same time, the depletion of cytosolic glutathione was delayed. In plasma samples, the natural extract inhibited the extent of lipid oxidation induced by the pro-oxidant agent cupric chloride (CuC12); a concomitant increase of plasma resistance to oxidation was observed as evaluated by conjugated diene formation.
The involvement of PC in the antioxidant protection of the APA extract against the oxidative damage was demonstrated by investigating the spectra changes of PC induced by AAPH or CuC12. The incubation of the extract with the oxidizing agents led to a significant decrease in the absorption of PC at 620 nm accompanied with disappearance of it blue color, thus indicating a rapid oxidation of the protein. In the light of these in vitro results, the potential clinical applications of this natural compound are under investigation.
Bioregulatory and Therapeutic Effects of Blue Green Algae Author(s): KUMAR K. ; LAKSHMANAN A. ; KANNAIYAN S. ; Indian Journal of Microbiology Indian J. Microbiol 2003, vol. 43, no1, pp. 9-16
Publisher: Association of Microbiologists of India, Hisar, INDE (1961) (Revue
Abstract In recent years, there has been a tremendous increase in the interest in micro algal metabolites. A novel 11-kDa virucidal protein, named cyanovirin- N (CV-N) has been isolated and sequenced from cultures of filamentous blue green alga, Nostoc ellipsosporum. This compound irreversibly inactivated diverse T-lymphocyte-tropic (T-tropic), laboratory adapted strains of HIV type 1, HIV type 2 and simian immunodeficiency virus (SIV). 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, indicating that at least some tumor cell types may be directly sensitive to killing by phycocyanin. Another fresh water blue-green alga, Phormidium tenue containing several diacyl-glycerol compounds effectively inhibited chemically induced skin tumors in mice. Studies on whole blue green algae in humans, mice, rats, cats and chickens have demonstrated their effect on phagocytosis, NK cell function and inflammation. Blue green algae in general contain a significant amount of carotenoids, namely beta carotene, lycopene and lutein, providing it good antioxidant properties. By their quenching action on reactive oxygen species, antioxidants carry intrinsic anti-inflammatory properties. Macrolides are one of the structural types often seen in Streptomyces-metabolites, and several major antibiotics belong to this class. Macrolides are also produced by blue green algae that include scytophycins from Scytonema sp. and tolytoxin from Tolypothrix conglutinata var. colorata. The coming years may witness some interesting developments in biotechnology of blue green algae which may give a new dimension to the therapeutic utilization of blue green algae.
Isolation of Three High Molecular Weight Polysaccharide Preparations with Potent Immunostimulatory Activity from Spirulina platensis, Aphanizomenon flos-aquae and Chlorella pyrenoidosa Planta Med 67 (2001) 737-742
Author(s): Nirmal Pugh, Samir A. Ross, Hala N. Elsohly, Mahmoun A. ElSohly, David S. Pasco
ABSTRACT This research describes the identification of three new high molecular weight polysaccharide preparations isolated from food-grade micro algae that are potent activators of human monocytes/macrophages: "immuline" from Spirulina platensis "Immunon" from Aphanizomenon flos-aquae; and "Immurella" from Chlorella pyrenoidosa. These polysaccharides are structurally complex and have estimated molecular weights above ten million Daltons. All three polysaccharides are highly water soluble and comprise between 0.5% and 2.0% of micro algal dry weight. Immunostimulatory activity was measured using transcription factor-based bioassay for nuclear factor kappa B (NF-kappa B) activation in THP-1 human monocytes/macrophages. Using this system the EC50 values for these micro algal polysaccharides are between 20 and 110 ng/ml (about 10pM). THP-1 activation was confirmed by measuring immune cytokine mRNA induction using reverse transcriptase-polymerase chain reaction (RT-PCR). Each polysaccharide substantially increased mRNA levels of interleukin and tumor necrosis factor-a (TNF-a). The polysaccharides are between one hundred and one thousand times more active for in vitro monocyte activation than polysaccharides preparation that are currently used clinically for cancer immunotherapy.
Favorable Effects of Blue-Green Algae Aphanizomenon flos-aquae on Rat Plasma Lipids Rafail I. Kushak, PhD, 1* Christian Drapeau, MS, 2 Elizabeth M. Van Cott, 1 Harland H. Winter1 1Combined Program in Pediatric Gastroenterology and Nutrition and Division of Laboratory Medicine Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 2Cell Tech, Klamath Falls, Oregon
JANA vol. 2 (3): 59-65
ABSTRACT Background: Polyunsaturated fatty acids (PUFAs) are essential for human health. There are indications that the lipid fraction of blue-green algae Aphanizomenon flos-aquae contains about 50% PUFA and may be a good dietary source of PUFA. The purpose of this study was to investigate the effect of diets supplemented with algae on blood plasma lipids. Methods: Rats were fed with four different semi synthetic diets: 1) standard, with 5% soybean oil; 2) PUFA-free with 5% coconut oil; 3) PUFA-free with 10% algae; 4) PUFA-free with 15% algae. After 32 days the levels of plasma fatty acids, triglycerides, and cholesterol were studied. Results: Rats fed the PUFA-free diet demonstrated an absence of linolenic acid (LNA) in plasma; however, supplementation with algae resulted in the same level of LNA as controls, increased levels of eicosapentaenoic acid and docosahexaenoic acid, and a decreased level of arachidonic acid. Dietary supplementation with 10% and 15% algae decreased the plasma cholesterol to 54% and 25% of the control level, respectively (p<0.0005). Plasma triglyceride levels decreased significantly (p<0.005) after diet supplementation with 15% algae. Conclusion:Algae Aphanizomenon flos-aquae is a good source of PUFA and because of potential hypocholesterolemic properties should be a valuable nutritional resource.
The Nicaragua Report Study on the Effects of Aphanizomenon flos-aquae on the Nutritional Status and School Performance of First, Second and Third Grade Children Attending the Mosenor Velez School in Nandaime, Nicaragua. July 1995 Author(s): Irma Sevilla, Nereyda Aguirre
ABSTRACT A study to determine the effects of Aphanizomenon flos-aquae on the nutritional status and school performance of first, second, and third grade children attending the Monsenor Velez School in Nandaime, Nicaragua, was conducted from June through December 1994 under the auspices of the Centro Comunitario in Nandaime and the Central American University in Nicaragua. A secondary objective of the study was to educate the population about the use of Aphanizomenon flos-aquae, basic nutrition, eating practices and about the value of the project. Conclusions: Although this research was conducted under sparse conditions with a minimum of resources, the researchers were able to achieve a thorough degree of control over the study conditions and accuracy of its conclusions. Based on the findings of this study, the researchers conclude that:
Eating Aphanizomenon flos-aquae improves the nutritional status of children considerably, reducing the prevalence of malnutrition.
School attendance, attitude and participation in class change positively due to the nutritional contribution of Aphanizomenon flos-aquae.
The clinical signs of malnutrition present in the children of the study group were reduced with the use of organic microalgae.
The children got ill less frequently, became more interested in academic activities, and their school attendance improved.
The study reflects the impact and health benefits of nutritional education, which led to the participant's acceptance of the algae.
Characterization of human monocytes activation by a water soluble preparation of Aphanizomenon flos-aquae JANA vol. 2 (3): 59-65 Phytomedicine vol. 8 (6): 445-453 Author(s): N. Pugh, D.S. Pasco
ABSTRACT Aphanizomenon flos-aquae (AFA) is fresh water microalgae that is consumed as a nutrient-dense food source and for its health enhancing properties. The current research characterizes the effect of a water soluble preparation from known agents that modulate the immune system. At 0.5 ng/ml the AFA extract robustly activated nuclear factor kappa B (NF-kappa B) directed luciferase expression in THP-1 human monocytic cells to levels at 50% of those achieved by maximal concentrations (10 ng/ml) of bacterial lipopoly saccharine (LPS). In addition, the AFA extract substantially increased mRNA levels of interleukin-1B (1L-1B) and tumor necrosis factor-(x (TNF-(x), and enhanced the DNA binding activity of NF-kappa B. The effects of AFA water soluble preparation were similar to the responses displayed by LPS, but clearly different from responses exhibited by tetradecanoyl phordol acetate (TPA) and interferon-gamma (INF-y). Pretreatment of THP-1 monocytes with factors known to induce hyproesponsiveness suppressed both AFA-dependent and LPS-dependent activation. These results suggest that the macrophage-activating properties of the AFA water soluble preparation are mediated through pathways that are similar to LPS-dependent activation.
Antimutagenic Properties of Fresh Water Blue-Green Algae Folia Microbiol (Praha), 39 (4), 1994, 301-303 Author(s): N. Lahitova, M. Doupovcova, J. Zvonar, J. Chandoga, G. Hocman
ABSTRACT The antimutagenic properties of whole fresh-water blue-green algae Aphanizomenon flos-aquae, marketed under the commercial "Alpha Sun" were tested using the Ames test. Simultaneous addition of both algae and Nitrovin (a mutagen) to the test medium did not reduce the mutagenic activity. On the other hand, addition of freeze-dried blue-green algae to the test medium 2-24 h before the application of mutagen reduced it mutagenic activity
Effects of the Blue-Green Algae Aphanizomenon flos-aquae (L.) Ralphs on Human Natural Killer Cells Author(s): Raffi Manoukin, Monica Citton, Patricia Huerta, Barbara Rhode, Christian Drapeau, Gitte S. Jensen
ABSTRACT In a double-blinded cross-over study, we evaluated the immediate (two hours) effect of Aphanizomenon flos-aqua (L.) Ralphs (AFA) on five normal healthy volunteers by comparing % NK cells in peripheral blood. The same volunteers consumed AFA and placebo on different days, and experiments were always done in the morning. The AFA dose was 1.5 g of freeze-dried algae. We found no differences in % NK cells after ingestion of placebo. In the same individuals, AFA ingestion resulted in a significant decrease if % NK cell in the circulation within two hours after AFA ingestion. The decreased level of NK cells was on average 63% of the starting percentage of circulating NK cells. In two donors, the expression of adhesion molecules of NK cells was tested after NK ingestion. The circulating NK cells showed increased expression of the adhesion receptor CD11b and the homing molecule L-selectin after AFA ingestion. We interpret this as a biological effect from yet uncharacterized molecular components within the AFA algae that regulates the recruitment of NK cells from blood into tissue. The observations may support previous speculations on the presence of neuropeptides or cytokine-like molecules within AFA. The rapid effect could indicate a direct action on NK cells, leading to increased ability to adhere to endothelium and migrate into lymphoid tissue. Absorbed components within ingested AFA could rapidly affect the endothelium in the gut mucosal-associated lymphoid tissue, leading to increased recruitment of specific cell subsets from blood. Alternatively, the action could occur via nerve stimulus to lymphoid tissue, thereby changing the tissue microenvironment, altering the endothelium or leading to secretion of chemokines. Both mechanisms would ultimately lead to an increased recruitment of NK cells from the blood, which after two hours leads to a measurable decrease of % NK cells in the circulation. Further studies are in progress to elucidate the short term and long term effects of AFA consumption on the human immune systems.
AFA Study in Ecylopedia of Dietary Supplements, August 2006
Blue-Green Algae (Cyanobacteria) Authors: Wayne W. Carmichael a; Mary Stukenberg a Affiliation: a Department of Biological Sciences, Wright State University, Dayton, Ohio, U.S.A. Published in: Encyclopedia of Dietary Supplements Published on: 15 August 2006 Subjects: Clinical Nutrition; Pharmacology; Abstract: In Asia, Africa, and parts of Central/South America, naturally occurring green and blue-green algae have been harvested and consumed for their nutritive properties for centuries. In western cultures, certain blue-green algae (cyanobacteria) have been an accepted source of food for about 30 yrs., in particular Spirulina (Arthrospira) platensis and Spirulina maxima. Beginning in the early 1980s, another blue-green species, Aphanizomenon flos-aquae (AFA), was adopted for similar uses. Both are rich in proteins, vitamins, essential amino acids, minerals, and essential fatty acids. Consumers of blue-green algae report a wide variety of putative effects such as mental clarity, increased energy, blood and colon cleansing, increased focus, particularly in children with attention deficit disorder, improved digestion, increased eye health, and healthier joints, and tissues. In the past ten years, owing largely to the strong anecdotal consumer testimony about them, studies have been conducted to verify not only their nutritional efficacy but also their potential pharmaceutical benefits as well.
Human studies have convincingly demonstrated pronounced photoprotective effects of 'natural' and synthetic antioxidants when applied topically before UVR exposure.
1: Curr Probl Dermatol. 2001;29:157-64. Protective effects of topical antioxidants in humans. Dreher F, Maibach H. Department of Dermatology, University of California, San Francisco, Calif., USA. Human studies have convincingly demonstrated pronounced photoprotective effects of 'natural' and synthetic antioxidants when applied topically before UVR exposure. Particularly with respect to UVB-induced skin damage such as erythema formation, the photoprotective effects of antioxidants are significant when applied in distinct mixtures in appropriate vehicles. Topical application of such combinations may result in a sustained antioxidant capacity of the skin, possibly due to antioxidant synergisms. And, since UVA-induced skin alterations are believed to be largely determined by oxidative processes [26], topical administration of antioxidants might be particularly promising [27, 28]. In fact, topical application of antioxidants or antioxidant mixtures resulted in a remarkable increase in the minimal dose to induce immediate pigment darkening after UVA exposure [18, 23] and diminished the severity of UVA-induced photodermatoses [22] in humans. In conclusion, regular application of skin care products containing antioxidants may be of the utmost benefit in efficiently preparing our skin against exogenous oxidative stressors occurring during daily life. Furthermore, sunscreening agents may also benefit from combination with antioxidants resulting in increased safety and efficacy of such photoprotective products [11, 29]. Publication Types: * Review * Review, Tutorial
The First Quantitative Evidence Proving the Efficacy of Supplemental Enzymes (PDF)
This research is the first comprehensive study thay shows that fungal digestive enzymes substantially increase the level of digestion in the lumen of the small intestine and bioaccessibility of proteins and carbohydrates. These results not only validate the use of digestive enzymes in cases of impaired digestion, but also show that most healthy adults can benefit by using a digestive enzyme supplement.
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EFFECT OF A KLAMATH ALGAE PRODUCT ("AFA-B12") ON BLOOD LEVELS OF VITAMIN B12 AND HOMOCYSTEINE IN VEGAN SUBJECTS: