Aphanizomenon flos-aquae (dietary supplement)

 Aphanizomenon flos-aquae (is a species of cyanobacteria (blue-green algae) which is commercially processed into a dietary supplement. Aphanizomenon flos-aquae (AFA) is known to contain nutrients including essential fatty acids, active enzymes, vitamins, amino acids, minerals, proteins, complex carbohydrates, and phytochemicals and is marketed as a nutritional supplement.

Biology
Like other cyanobacteria and plants, AFA uses photosynthesis to produce the food material (glycogen) that is stored and utilized by the cell. While plants' cell walls are mainly cellulose, AFA's cell walls are composed of peptidoglycan (carbohydrates and peptides), the typical cell wall material of bacteria. Therefore, the designation "cyanobacteria" (Latin, cyano = blue-green) refers to the blue-green coloration of this bacterial subdivision, including AFA.

The cellular structure of AFA is that of a simple prokaryote. Most cyanobacteria are highly efficient photosynthesizers, even more so than plants. Algae utilize light energy from the sun, carbon dioxide from the air, and water to synthesize proteins, carbohydrates, and lipids. AFA is also able to directly use molecular nitrogen from the air to produce proteins and other nitrogen-containing biomolecules. This ability is widespread in prokaryotes, but unknown in eukaryotes.

Potential toxicity
Aphanizomenon flos-aquae as a species has both toxic and non-toxic forms. While benefits have been indicated, toxicity has been shown in some strains of the species Aphanizomenon flos-aquae, with cylindrospermopsin and saxitoxins present, and microcystins found contaminating AFA dietary supplements. The World Health Organization's Guidelines For Drinking Water Quality note Anatoxin-a, saxitoxins, and cylindrospermopsins are present in the Aphanizomenon genus. At least one strain of AFA labeled as toxic has been show to have been misclassified. Colony-forming morphology is one of the characteristics of the non-toxic species Aphanizomenon flos-aquae; conversely, toxin-producing species of Aphanizomenon are not known to form colonies. Algologists Li and Carmichael noted colony formation, or lack thereof, and other morphologic distinctions when comparing Aphanizomenon flos-aquae with toxin-producing species of Aphanizomenon. Their genetic comparison of Aphanizomenon flos-aquae to other species in the genus Aphanizomenon indicates dissimilarity between Aphanizomenon flos-aquae and toxin-producing Aphanizomenon species.

History
Cyanobacteria have been a staple in the diets of many cultures and have been used for both food and commerce by indigenous peoples all over the globe, from Africa and Asia to the Americas, from the Chinese to the Aztecs and Mayans.

Aphanizomenon flos-aquae began to be harvested as a human dietary supplement in the early 1980s. In 1998 a dry weight of approximately 1 million lbs (2.2 million kg) of AFA was harvested for the subsequent production of supplements by a number of commercial harvesters. Commercial standards vary greatly in terms of documenting product composition to the consumer.

Today, AFA is marketed as a nutrient-dense food, harvested primarily from Upper Klamath Lake in North America.

Harvesting and processing
Cyanobacteria as a crop are sensitive to heat, light, and rapid spoilage. Some native cultures in Africa and the Americas used simple sun-drying methods for preservation, but it is likely that a significant amount of the nutritional value was lost in the process because of exposure to extreme heat during harvesting and processing. The methods for harvesting and processing used to make cyanobacteria available for consumption today are critical factors in the quality and safety of the finished product.

AFA is processed by screening to remove debris, testing for contaminating species, storing at the optimum temperature, and drying by a method that preserves nutrients. As with any crop, differences exist with regard to harvesting procedures, quality control against contaminating species, adherence to proper processing to protect nutrients from degradation, and attention to adequate storage conditions of the processed algae.

Nutritional value
Cyanobacteria are often marketed as a source of nutrients such as vitamins, minerals, essential fatty acids (including omega 3 fatty acids), beta-carotene, chlorophyll, phycocyanin, active enzymes, amino acids, proteins, complex sugars, phytonutrients, and other bioactive components.

The nutrient content of Aphanizomenon flos-aquae is subject to much variation due to diverse habitats, environmental factors, and harvesting procedures, all of which influence the nutritional value; for example, altitude, temperature, and sun exposure can greatly affect lipid and pigment composition. As more is learned about the components of different cyanobacterial species, growers and harvesters are better able to determine the optimal growth conditions for obtaining optimal yields.

Vitamins
 Aphanizomenon flos-aquae has been shown to contain varying amounts at least 13 vitamins: vitamin A (beta-carotene), vitamin C (ascorbic acid), vitamin E, vitamin K, and many of the B-complex vitamins including B1 (thiamin), B2 (riboflavin), B6 (pyridoxine), choline, biotin, niacin, folic acid, pantothenic acid, and B12 (cobalamin).

Minerals
Aphanizomenon flos-aquae contains minerals and trace minerals (including calcium, chloride, chromium, copper, iron, magnesium, manganese, phosphorus, potassium, sodium, and zinc). Whether or not AFA microalgae contain a balance of bioavailable minerals and trace minerals depends on the mineral content of their growth environment.

Protein
AFA is approximately 60% protein by dry weight.

Essential fatty acids
Approximately 45% of the lipids (fats) of AFA are essential fatty acids. Aphanizomenon flos-aquae contains a balance of both linoleic acid (LA, an omega-6 fatty acid) and alpha-linolenic acid (ALA, an omega-3 fatty acid). Researchers at Massachusetts General Hospital who studied AFA's fat content concluded that AFA "should be a valuable nutritional resource." AFA raises the blood levels of the good fatty acids more than would be expected based on its ALA content alone. They speculated that some micronutrients may enhance fatty acid utilization. The levels of "good" fatty acids (ALA, EPA, DHA) went up while the levels of arachidonic acid went down.

Photosynthetic pigments
Chlorophyll is the green pigment found in plants that is responsible for the production of oxygen through the process of photosynthesis. Chlorophyll is a significant phytonutrient as well as a powerful antioxidant. AFA contains 1 to 2% chlorophyll (dry weight). AFA is also a source of phycocyanin (PC), a photosynthetic pigment with antioxidant and anti-inflammatory properties that contributes the 'blue' to blue-green algae.

Phenylethylamine
AFA contains phenylethylamine (PEA), a compound that helps alleviate depression, increase concentration, and elevate mood. PEA contributes to the health of all bodily functions.

Evidence of health effects
Many claims are based on research done on individual nutrients that Aphanizomenon flos-aquae contains, such as vitamins, minerals, chlorophyll, various antioxidants, and others. For example, polyunsaturated fatty acids (PUFAs), which are very important in maintaining membrane fluidity, comprise up to 10% of AFA's dry weight. Animal research at Massachusetts General Hospital and Harvard Medical School found that AFA microalgae raised blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA are known to contribute to optimal functioning of numerous organ systems, including the nervous system. The researchers found that AFA was more effective than soybean oil, a good source of PUFAs, at raising blood levels of these omega-3 fatty acids.

A team at the Royal Victoria Hospital, Montreal, Canada, demonstrated that consumption of AFA results in an immediate change in the trafficking of immune cells. The effect is transient and cell-type specific. An extensive body of data documents that long-term consumption does not lead to hyper-stimulation of the immune system. According to researchers, AFA blue-green algae make natural killer cells "patrol" better throughout the body. These effects were seen when using a low oral dose of algae (1.5 gram), corresponding to a low amount of food supplementation.

The special molecule that provides the blue color in blue-green algae is called phycocyanin. Depending on the algae source, the amount of phycocyanin can amount to up to 15% of the dry weight of the algae. Phycocyanin has antioxidant and anti-inflammatory effects. One study evaluated the ability of a novel natural extract of AFA enriched with phycocyanin to protect normal human erythrocytes and blood 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 (CuCl2); a concomitant increase of plasma resistance to oxidation was observed as evaluated by conjugated diene formation.

In recent years, there has been an increase of interest in microalgal metabolites. 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. Blue-green algae in general contain a significant amount of carotenoids, namely beta-carotene, lycopene, and lutein, providing microalgae with antioxidant properties. By their quenching action on reactive oxygen species, antioxidants carry intrinsic anti-inflammatory properties.

Other research describes the identification of three new high molecular weight polysaccharide preparations isolated from food-grade microalgae that are effective activators of human monocytes/macrophages, including "Immunon" from Aphanizomenon flos-aquae. Immunostimulatory activity was measured using transcription factor-based bioassay. Each polysaccharide studied in this research, including AFA, substantially increased mRNA levels of interleukin and tumor necrosis factor-a (TNF-a). These polysaccharides are between one hundred and one thousand times more active for in vitro monocyte activation than polysaccharide preparations that are currently used clinically for cancer immunotherapy.

Research also characterizes the effect of a water-soluble preparation from known agents that modulate the immune system. One such study suggests that the macrophage-activating properties of an AFA water-soluble preparation are mediated through pathways that are similar to LPS-dependent activation.

The antimutagenic properties of whole, fresh-water AFA 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. Addition of freeze-dried AFA to the test medium 2–24 hours before the application of the mutagen reduced mutagenic activity.

An ethanol extract of AFA-cellular concentrate has been shown to increase stem cell proliferative action when incubated with human adult bone marrow cells or human CD34+ hematopoietic progenitors in culture. The preliminary study suggests that the ethanol extract of AFA cellular concentrate may act to promote proliferation of human stem cell populations.

Organic certification
Organic certification can be a lengthy and complicated process, and it is achieved only through strict compliance with established official regulations. Requirements vary from country to country, and generally involve a stringent set of production standards for growing, storage, processing, packaging, and shipping. It is up to individual algae producers to apply for and secure organic certification by adherence to the certifying agency's standards.