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"Give with a free hand, but give only your own."
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- Aphanizomenon flos-aquae (AFA) -


General Information:

Names:
Wikipedia entry:
Dr. Ray Shahelien entry: 

********************************************************************************************
Observations:

Aphanizomenon flos-aquae (AFA)

See also
Inflammation

Most of the information you will find on the Internet about AFA is from sellers of AFA or AFA extracts.  Obviously, they have a pro-AFA bias, especially when it comes to their particular brand.  The next most common group are those trying to debunk the whole idea.  A rare few in the middle have made an almost unbiased, but totally subjective report.  What I am not finding are many posts from actual users on message boards telling of their experience with taking AFA for a neurodegenerative disease.  So, read carefully, and do your homework!

Blue Green Algae health benefit
Blue green algae are not really algae, but they actually are more closely related to bacteria. Because they are photosynthetic and aquatic, cyanobacteria are often called "blue-green algae". This name is convenient for talking about organisms in the water that make their own food, but does not reflect any relationship between the cyanobacteria and other organisms called algae. Cyanobacteria are relatives of the bacteria, not eukaryotes. Cyanobacteria are aquatic and photosynthetic, that is, they live in the water, and can manufacture their own food. Because they are bacteria, they are quite small and usually unicellular, though they often grow in colonies large enough to see. They have the distinction of being the oldest known fossils, more than 3.5 billion years old. Cyanobacteria are still around; they are one of the largest and most important groups of bacteria on earth.

The two types of Blue-Green Algae

Blue green algae are an important part of the food chain in lakes and ponds worldwide. The two main blue-green types are Spirulina and Aphanizomenon flos-aquae (AFA). AFA is harvested from Upper Klamath Lake in Oregon and then freeze-dried and sold in capsules and other forms...
http://www.raysahelian.com/bluegreenalgae.html

(WO/2008/000430) ALPHANIZOMENON [sic] FLOS AQUAE PREPARATION, EXTRACTS AND PURIFIED COMPONENTS THEREOF FOR THE TREATMENT OF NEUROLOGICAL, NEURODEGENERATIVE AND MOOD DISORDERS

Inventors:  SCOGLIO, Stefano; (IT).
            CANESTRARI, Franco; (IT).
            BENEDETTI, Serena; (IT).
            BENEDETTI, Yanina; (IT).
            DELGADO-ESTEBAN, Maria; (ES).

WO 2008000430 20080103


APHANIZOMENON FLOS AQUAE PREPARATION, EXTRACTS AND PURIFIED COMPONENTS THEREOF FOR THE TREATMENT OF NEUROLOGICAL, NEURODEGENERATIVE AND MOOD DISORDERS

The present invention relates to the microalga Aphanizomenon Flos Aquae Aquae Ralfs ex Born. & Flah. Var. flos aquae (AFA Klamath). More precisely, the invention provides extracts of AFA Klamath and purified components thereof useful for the prevention or treatment of neurological, neurodegenerative and mood conditions or diseases... Phenylethylamine (PEA) is an endogenous amine synthesized by decarboxylation of phenylalanine in dopaminergic neurons of the nigrostriatal system, and may act as a neuromodulator of catecholamine neurotransmission in the brain... Moreover, once ingested PEA can easily pass through the blood-brain barrier and stimulate the release of dopamine from the nigrostriatal tissue even at low dosages...

Description of the invention

The invention is based on the identification, in the microalga Aphanizomenon Flos Aquae Aquae Ralfs ex Born. & Flah. Var. flos aquae (AFA Klamath), of substances that, alone or in combination, exert beneficial effects on various neurological diseases, conditions, dysfunctions or disorders, including neurodegenerative diseases such as Alzheimer's and Parkinson's, multiple sclerosis, hyperactivity and attention deficit disorders (ADHD), autism, depression, memory deficit and mood disturbances. In particular, it has been found that AFA Klamath microalga contains, besides phenylethylamine, which is a neuromodulator characterized by dopaminergic and noradrenergic activity, specific molecules which quite surprisingly proved to be very effective inhibitors of the enzyme monoaminoxidase B (MAO-B), namely: a) the specific AFA-phytochrome; b) the AFA-phycobiliprotein complex containing a phycobilisome formed by C-phycocyanin (C-PC) and phycoerythrocyanin (PEC, including its chromophore phycoviolobilin or PVB) ("AFA-phycocyanins"); c) mycosporine-like amino acids or MAAs. This finding is very important since the PEA contained in the algae, unless protected by MAO-B inhibitors, would be rapidly destroyed upon ingestion by the MAO-B enzyme...

...the AFA Klamath extract... is prepared by [either]: a) freezing the freshly harvested AFA alga and thawing it, or, if... dried AFA powder, sonicating the water-diluted AFA powder to disrupt the cells; b) centrifuging the product of step a) to separate the supernatant... from the precipitate...; c) collecting the supernatant containing the water-soluble components.

The resulting product is an extract (indicated as "Basic Extract") which concentrates PEA as well as other synergic molecules such as the AFA phytochrome, the AFA-phycocyanins, and the MAAs. For example, whereas Klamath microalga has a natural content of PEA ranging from 2 to 4 mg/gr, the Basic Extract increases this concentration to a level ranging from 9 to 11 mg/gr (HPLC analysis).

It is possible to further purify the extract by passing it through an ultra- filtration system...

The Basic Extract obtained by steps a) to c), i.e. without ultra-filtration, is generally preferred as it contains the most appropriate amounts of PEA, AFA-phytochrome, AFA-PC and MAAs. Moreover, this Basic Extract also includes substances such as chlorophyll and carotenes, even though in a reduced proportion, contributing to its antioxidant and anti-inflammatory properties...
http://www.wipo.int/pctdb/en/wo.jsp?WO=2008000430&IA=EP2007005622&DISPLAY=DESC

(WO/2010/120992) METHOD OF SEPARATION OF ALGAL BIOMASS FROM AQUEOUS OR MARINE CULTURE

Marine Toxins :: analysis
http://lib.bioinfo.pl/meid:37072

Bioactive Compounds From Cyanobacteria and Microalgae: An Overview
Critical Reviews in Biotechnology
Posted on: Sunday, 23 October 2005, 03:01 CDT

By Singh, Sawraj; Kate, Bhushan N; Banerjee, U C

ABSTRACT Cyanobacteria (blue-green algae) are photosynthetic prokaryotes used as food by humans. They have also been recognized as an excellent source of vitamins and proteins and as such are found in health food stores throughout the world. They are also reported to be a source of fine chemicals, renewable fuel and bioactive compounds. This potential is being realized as data from research in the areas of the physiology and chemistry of these organisms are gathered and the knowledge of cyanobacterial genetics and genetic engineering increased. Their role as antiviral, anti- tumour, antibacterial, anti-HIV and a food additive have been well established. The production of cyanobacteria in artificial and natural environments has been fully exploited. In this review the use of cyanobacteria and microalgae, production processes and biosynthesis of pigments, colorants and certain bioactive compounds are discussed in detail. The genetic manipulation of cyanobacteria and microalgae to improve their quality are also described at length.
http://www.redorbit.com/news/science/281044/bioactive_compounds_from_cyanobacteria_and_microalgae_an_overview/


B12:

Effect of a Klamath algae product ("AFA-B12") on blood levels of vitamin B12 and homocysteine in vegan subjects: a pilot study.
Int J Vitam Nutr Res. 2009 Mar;79(2):117-23.
...Compared to the control period, in the intervention period participants improved their vitamin B12 status, significantly reducing Hcy blood concentration (p=0.003). In conclusion, the Klamath algae product AFA-B12 appears to be, in a preliminary study, an adequate and reliable source of vitamin B12 in humans.
PMID: 20108213 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/20108213

Low vitamin B12 levels may cause a whole host of problems, including neurological disorders that mimick other diseases.

¤ Adult Stem Cell Enhancement, StemEnhance,
NT-020, Stem Naturals:

Honestly, I don't know if StemEnhance, NT-20 or products like it actually "promotes proliferation of human hematopoietic stem cells" or would help repair the damage caused by neurodegenerative diseases or not.  I hope they do.  I hope we find something that helps.  But I don't know.  I am not implying that these products work or do not work.  I am not endorsing or denouncing these products. I just thought that you would like to know that these things exist so you can do your own research and make up your own mind.

Product information about StemEnhance from the company's web site:

When you take two capsules, the ingredients help to support the release of stem cells from the bone marrow into the bloodstream. Through a natural process, those stem cells then travel to areas of the body where they are most needed... Adult stem cells are most abundantly found in bone marrow. Stem cells circulate and function to replace dysfunctional cells, thus fulfilling the natural process of maintaining optimal health. StemEnhance supports the release of adult stem cells from bone marrow into circulation...
StemTech HealthSciences of Klamath Falls, Oregon
http://www.stemtechhealth.com/

More information is available from distributors:

Components in AFA responsible for its various health benefits include:
    * phenylethylamine (PEA), responsible for providing a feeling of mental energy,
    * phycocyanin, responsible for the antioxidant and anti-inflammatory properties,
    * a polysaccharide, responsible for supporting the immune system, and
    * an L-selectin ligand, responsible for supporting the release of stem cells from the bone marrow.

StemEnhance™ is a 5:1 concentrate, that blends two compounds extracted from of AFA.  One extract, containing an L-selectin ligand, supports the natural release of stem cells (CD34+ cells) from the bone marrow.  The other extract, a polysaccharide-rich fraction named Migratose™, may support the migration of stem cells out of the blood and into stressed tissues.

Formulated specifically to support stem cell physiology; StemEnhance™ also concentrates other compounds unique to AFA, bringing unique support for the whole body.
http://www.essential-vitamins.com/stemTech/details.html

I have no way of knowing at this time if it performs as advertised. I hope it helps because we're going to try it. [12/7/10] This decision was based not on the product advertising, but on other research articles, patents, and the report by Dr. Gabriel Cousens (later in this section).

But, not everyone is enthusiastic about the product:

PatientsLikeMe.com
StemEnhance (blue-green algae) Treatment Report
http://www.patientslikeme.com/all/treatments/show/1948-stem-enhance?brand=t


StemTech's Dubious Claims

StemTech HealthSciences
... would like you to believe that StemEnhance™ can help many health problems. The product's label describes it as an extract of Aphanizomenon flos aquae, a species of blue-green algae harvested from a lake in Klamath Lake in Oregon. The retail price for a bottle of 60 capsules is about $60. The recommended dosage is 2-4 capsules per day.
Before taking any product, it is advisable to know whether it has been proven safe and effective for its intended purpose(s). With respect to StemEnhance, the following questions would have to be answered:

    What evidence shows that taking StemEnhance will improve anyone's health?
    Has any study shown that people improved their health as a result of taking it?
    What evidence shows that StemEnhance is safe for long-term use?
    How can users be certain that long-term use will not cause abnormal tissue growth?
    For whom is the product advisable?
    Who should not take it?

Background History

StemEnhance appears to be the brainchild of Christian Drapeau and Gitte S. Jensen, Ph.D. Drapeau is director of Research and Development for Desert Lake Technologies, of Klamath Falls, Oregon. Desert Lake's Web site says that before that, he spend five years as director for research and development for Cell Tech International, a multilevel company whose primary products are derived from blue-green algae. The Web site also states that Drapeau holds a master of science degree in neurology and neurosurgery. Jensen is director of research for Holger NIS Inc., of Port Dover, Ontario, Canada. Holger's Web site states that her Ph.D. is in immunology and that she has done research projects on immunology, cancer biology and metastasis, and nutrition.
http://www.mlmwatch.org/04C/Stemtech/stemtech.html


The Trial of the Blue-Green Algae Eaters (1986)
Carol Ballantine
...The algae was harvested from the lake when the species Aphanizomenon flos-aquae was predominant. Aphanizomenon flos-aquae has been found to produce a toxin that is a powerful neuromuscular blocking agent. In laboratory studies it has caused animals to stop breathing. The algae produces the toxin during its most active growth state, which is also when it is most likely to be harvested...
Carol Ballentine is a member of FDA's public affairs staff. This article is reprinted from the July-August 1986 issue of FDA Consumer.
http://www.mlmwatch.org/05FDA/kclabs.html

The above article states that "Aphanizomenon flos-aquae has been found to produce a toxin".  I haven't been able to find anything that confirms this.  Quite the contrary, I've found articles that say that some strains of cyanobacteria that do produce toxins were mis-classified as AFA (See the paper Taxonomic re-evaluation of Aphanizomenon flos-aquae NH-5 below)Aphanizomenon ovalisporum is a toxic blue-green alga in the same family as A.flos-aque. Such a glaring, critical error makes me dubious of all the facts presented in the story.  I want the truth, not biased opinion either from the makers and distributors of AFA products, or from the FDA.  The FDA is hardly an unbiased third party.  It is a granter of monopoly, and a political animal, subject to the influence of politicians, the whims of bureaucrats, and purchased favors from those with fist-fulls of dollars.


Taxonomic re-evaluation of Aphanizomenon flos-aquae NH-5 based on morphology and 16S rRNA gene sequences
Renhui Li, Wayne W. Carmichael, Yongding Liu and Makoto M. Watanabe
Hydrobiologia
Volume 438, Numbers 1-3, 99-105, DOI: 10.1023/A:1004166029866

Abstract

The taxonomy of Aphanizomenon flos-aquae strain NH-5, a producer of cyanotoxins, was re-evaluated by comparison with six other Aphanizomenon strains using morphological characteristics and 16S rRNA gene sequences. Strain NH-5 was concluded to be improperly identified as Aph. flos-aquae based upon (1) lack of bundle formation in the trichomes, (2) location of akinetes next to heterocytes, (3) lower similarities (less than 97.5%) in the 16S rRNA gene sequences relative to Aph. flos-aquae strains, and (4) comparison within a phylogenetic tree constructed from 16S rRNA gene sequences. The Aphanizomenon strains investigated in this study are classified to four morphological groups as described by the classical taxonomy of Komárek & Kovácik (1989). This classification was supported from the phylogenetic results of 16S rRNA gene sequences. This study also discusses the generic boundaries between Aphanizomenon and Anabaena.
http://www.springerlink.com/content/p28521u04518l453/

While A.flos-aquae itself doesn't produce toxins, there is a possibility that it can be contaminated:

Risk Assessment of Microcystin in Dietary Aphanizomenon flos-aquae
David J. Schaeffera, 1, Phyllis B. Malpasa, 2 and Larry L. Bartonb
Available online 2 April 2002.

Abstract

Aphanizomenon flos-aquae, a cyanobacterium that is marketed as a health food supplement, is harvested from natural blooms in Klamath Lake (Oregon) that are occasionally contaminated by Microcystis spp. Regulatory agencies in several countries are developing regulations to control the amount of microcystin in drinking water and other products, including products produced from A. flos-aquae. Regulation of microcystin (MC), a toxin produced by Microcystis spp. that is potentially present in natural culture of A. flos-aquae, should be based on studies in which a test species is exposed to the natural mixture of these cyanobacteria. A 1984 feeding trial to determine the effects of high dietary levels of A. flos-aquae on reproduction and development of mice is reanalyzed in light of recent analyses for microcystin-LR (MCLR) in the diets of those mice. Young adult mice consuming up to 333 µg MCLR/kg body weight (bw)/day exhibited no adverse effects on growth and reproduction, fetal development, and survival and organ weights of neonates. Based on a NOAEL of 333 µg MCLR/kg bw/day, a safety factor of 1000, consumption of 2 g/day of A. flos-aquae by a 60-kg adult, the safe level of MCLR as a contaminant of A. flos-aquae products is calculated to be 10.0 µg MCLR/g.
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WDM-45GWF99-18&_user=10&_coverDate=09%2F30%2F1999&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=35e803c068e3d6b8704617e039ae6963&searchtype=a


An article in the August 1995 issue of Vegetarian Times Blue-Green Algae Blues (Pg. 18) quotes the FDA article The Trial of the Blue-Green Algae Eaters (1986) by Carol Ballantine. The article also states "Two studies published by biologists in 1960 and 1971, however, found samples of Klmath Lake algae to be elthal [lethal?] to fish and white mice."  But they didn't provide references.  How many people are actually going to check the cited articles?  These may be the ones.

11. Gentile JH. 1971. Blue green and green algal toxins, pp. 27-67 in vol. 7 of Microbial Toxins, Kadis S, Ciegler A, Ajl SJ, Eds., Academic Press, NY.

Phinney HK, Peek CA. 1961. Klamath Lake, an instance of natural enrichment. Trans. Sem. on Algae and Metropolitan Wastes. Robert A. Taft Sanitary Engineering Center, Cincinnati, OH.

I will have to obtain copies of the articles to find out the algae they discuss is A.flos-aquae, and decide for myself it they really apply.

Here is a rather interesting article, but again, it is all discussion of what might be and what could be.  No one is actually trying anyting... doing any experiments:

For sale: Stem cell enhancers
Dietary supplement claims to boost circulating stem cells, but is it safe?
By Kerry Grens
The Scientist on "StemEnhance"
[Published 15th May 2007 02:49 PM GMT]
...And if the product does what it says, [stimulate the release of adult stem cells] it may not be safe, according to Frishman. One of the risks of taking a stem cell enhancer is that it could activate dormant cancer cells, he told The Scientist. There are other stem cell enhancing drugs that target particular cell types, such as granulocyte colony-stimulating factor, which elevates white blood cells after chemotherapy. "Here [with StemEnhance] you're giving a general stem cell booster," Frishman said. "Some people might have occult malignancies and all of a sudden you're giving them a stem cell booster.
http://sci.rutgers.edu/forum/archive/index.php/t-82032.html
http://sci.rutgers.edu/forum/showthread.php?t=82032

You see, one theory is that metastatic cancer has "stem cells" too.  The idea is that not all cancer cells can prolifrate, but only the cancer stem cells.  These have a different life cycle than "ordinary" cancer cells, so chemotherapy to treat them must be taylored to it.  In general, they say chemotherapy should be given longer to catch the stem cells that are not destroyed with the "ordinary" cancer cells. [From an article on ScienceDaily.com???]

Mobilization of bone marrow stem cells with StemEnhance improves muscle regeneration in cardiotoxin-induced muscle injury.
Drapeau C, Antarr D, Ma H, Yang Z, Tang L, Hoffman RM, Schaeffer DJ.
Cell Cycle. 2010 May;9(9):1819-23. Epub 2010 May 17.

STEMTech HealthSciences, Inc., San Clemente, CA, USA. cdrapeau@stemtechmail.com
Abstract

Bone marrow-derived stem cells have the ability to migrate to sites of tissue damage and participate in tissue regeneration. The number of circulating stem cells has been shown to be a key parameter in this process. Therefore, stimulating the mobilization of bone marrow stem cells may accelerate tissue regeneration in various animal models of injury. In this study we investigated the effect of the bone marrow stem cells mobilizer StemEnhance (SE), a water-soluble extract of the cyanophyta Aphanizomenon flos-aquae (AFA), on hematopoietic recovery after myeloablation as well as recovery from cardiotoxin-induced injury of the anterior tibialis muscle in mice. Control and SE-treated female mice were irradiated, and then transplanted with GFP(+) bone marrow stem cells and allowed to recover. Immediately after transplant, animals were gavaged daily with 300 mg/kg of SE in PBS or a PBS control. After hematopoietic recovery (23 days), mice were injected with cardiotoxin in the anterior tibialis muscle. Five weeks later, the anterior tibialis muscles were analyzed for incorporation of GFP(+) bone marrow-derived cells using fluorescence imaging. SE significantly enhanced recovery from cardiotoxin-injury. However, StemEnhance did not affect the growth of the animal and did not affect hematopoietic recovery after myeloablation, when compared to control. This study suggests that inducing mobilization of stem cells from the bone marrow is a strategy for muscle regeneration.

PMID: 20404540 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/20404540

PDF of full article:
http://www.landesbioscience.com/journals/cc/article/DrapeauCC9-9.pdf

At least one of the authors of the above article,
Mobilization of bone marrow stem cells has significant financial interest in the company that produces StemEnhance.


Mobilization of human CD34+ CD133+ and CD34+ CD133(-) stem cells in vivo by consumption of an extract from Aphanizomenon flos-aquae--related to modulation of CXCR4 expression by an L-selectin ligand?

Jensen GS, Hart AN, Zaske LA, Drapeau C, Gupta N, Schaeffer DJ, Cruickshank JA.
Cardiovasc Revasc Med. 2007 Jul-Sep;8(3):189-202

Abstract

OBJECTIVE: The goal of this study was to evaluate effects on human stem cells in vitro and in vivo of an extract from the edible cyanobacterium Aphanizomenon flos-aquae (AFA) enriched for a novel ligand for human CD62L (L-selectin).

EXPERIMENTAL APPROACH: Ligands for CD62L provide a mechanism for stem cell mobilization in conjunction with down-regulation of the CXCR4 chemokine receptor for stromal derived factor 1. Affinity immunoprecipitation was used to identify a novel ligand for CD62L from a water extract from AFA. The effects of AFA water extract on CD62L binding and CXCR4 expression was tested in vitro using human bone marrow CD34+ cells and the two progenitor cell lines, KG1a and K562. A double-blind randomized crossover study involving 12 healthy subjects evaluated the effects of consumption on stem cell mobilization in vivo.

RESULTS: An AFA extract rich in the CD62L ligand reduced the fucoidan-mediated externalization of the CXCR4 chemokine receptor on bone marrow CD34+ cells by 30% and the CD62L+ CD34+ cell line KG1A by 50% but did not alter the CXCR4 expression levels on the CD34(-) cell line K562. A transient, 18% increase in numbers of circulating CD34+ stem cells maximized 1 hour after consumption (P<.0003). When 3 noncompliant volunteers were removed from analysis, the increase in CD34+ cells was 25% (P<.0001).

CONCLUSION: AFA water extract contains a novel ligand for CD62L. It modulates CXCR4 expression on CD34+ bone marrow cells in vitro and triggers the mobilization of CD34+ CD133+ and CD34+ CD133(-) cells in vivo.

PMID: 17765649 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/17765649

At least one of the authors of the above article, Mobilization of human CD34+ CD133+ and CD34+ CD133(-) stem cells has significant financial interest in the company that produces StemEnhance.

Consumption of Aphanizomenon flos-aquae has rapid effects on the circulation and function of immune cells in humans.
Drapeau, C. JANA 2000, 2, 50-58.
[NEED PUBMED CITATION]

The following papers are about AFA and a product called
"NT-020" that is purported to promote "proliferation of human hematopoietic stem cells".

Effects of blue-green algae extracts on the proliferation of human adult stem cells in vitro: a preliminary study.
Shytle DR, Tan J, Ehrhart J, Smith AJ, Sanberg CD, Sanberg PR, Anderson J, Bickford PC.
Department of Neurosurgery, USF, Tampa, FL, USA.
Med Sci Monit. 2010 Jan;16(1):BR1-5.

Abstract

BACKGROUND: Adult stem cells are known to have a reduced restorative capacity as we age and are more vulnerable to oxidative stress resulting in a reduced ability of the body to heal itself. We have previously reported that a proprietary nutraceutical formulation, NT-020, promotes proliferation of human hematopoietic stem cells in vitro and protects stem cells from oxidative stress when given chronically to mice in vivo. Because previous reports suggest that the blue green algae, Aphanizomenon flos-aquae (AFA) can modulate immune function in animals, we sought to investigate the effects of AFA on human stem cells in cultures.

MATERIAL/METHODS: Two AFA products were used for extraction: AFA whole (AFA-W) and AFA cellular concentrate (AFA-C). Water and ethanol extractions were performed to isolate active compounds for cell culture experiments. For cell proliferation analysis, human bone marrow cells or human CD34+ cells were cultured in 96 well plates and treated for 72 hours with various extracts. An MTT assay was used to estimate cell proliferation.

RESULTS: We report here that the addition of an ethanol extract of AFA-cellular concentrate further enhances the stem cell proliferative action of NT-020 when incubated with human adult bone marrow cells or human CD34+ hematopoietic progenitors in culture. Algae extracts alone had only moderate activity in these stem cell proliferation assays.

CONCLUSIONS: This preliminary study suggests that NT-020 plus the ethanol extract of AFA cellular concentrate may act to promote proliferation of human stem cell populations.

PMID: 20037479 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/20037479


Spirulina promotes stem cell genesis and protects against LPS induced declines in neural stem cell proliferation.
Bachstetter AD, Jernberg J, Schlunk A, Vila JL, Hudson C, Cole MJ, Shytle RD, Tan J, Sanberg PR, Sanberg CD, Borlongan C, Kaneko Y, Tajiri N, Gemma C, Bickford PC.
Department of Molecular Pharmacology and Physiology, College of Medicine, University of South Florida, Tampa, Florida, United States of America.
PLoS One. 2010 May 5;5(5):e10496.

Abstract

Adult stem cells are present in many tissues including, skin, muscle, adipose, bone marrow, and in the brain. Neuroinflammation has been shown to be a potent negative regulator of stem cell and progenitor cell proliferation in the neurogenic regions of the brain. Recently we demonstrated that decreasing a key neuroinflammatory cytokine IL-1beta in the hippocampus of aged rats reversed the age-related cognitive decline and increased neurogenesis in the age rats. We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress. The objectives of this study were to determine if spirulina could protect the proliferative potential of hippocampal neural progenitor cells from an acute systemic inflammatory insult of lipopolysaccharide (LPS). To this end, young rats were fed for 30 days a control diet or a diet supplemented with 0.1% spirulina. On day 28 the rats were given a single i.p. injection of LPS (1 mg/kg). The following day the rats were injected with BrdU (50 mg/kg b.i.d. i.p.) and were sacrificed 24 hours after the first injection of BrdU. Quantification of the BrdU positive cells in the subgranular zone of the dentate gyrus demonstrated a decrease in proliferation of the stem/progenitor cells in the hippocampus as a result of the LPS insult. Furthermore, the diet supplemented with spirulina was able to negate the LPS induced decrease in stem/progenitor cell proliferation. In a second set of studies we examined the effects of spirulina either alone or in combination with a proprietary formulation (NT-020) of blueberry, green tea, vitamin D3 and carnosine on the function of bone marrow and CD34+ cells in vitro. Spirulina had small effects on its own and more than additive effects in combination with NT-020 to promote mitochondrial respiration and/or proliferation of these cells in culture. When examined on neural stem cells in culture spirulina increased proliferation at baseline and protected against the negative influence of TNFalpha to reduce neural stem cell proliferation. These results support the hypothesis that a diet enriched with spirulina and other nutraceuticals may help protect the stem/progenitor cells from insults.
PMID: 20463965 [PubMed - indexed for MEDLINE]PMCID: PMC2864748
http://www.ncbi.nlm.nih.gov/pubmed/20463965
Full text at:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864748/?tool=pubmed

It appears that we have here yet another "cocktail" to play with:

Blueberry
Green Tea
Vitamin D3
Carnosine
Spirulina or AFA

These researchers claim that their "proprietary formulation" either with, or without spirulina, "increased proliferation at baseline and protected against the negative influence of TNFalpha to reduce neural stem cell proliferation".

NT-020, a Natural Therapeutic Approach to Optimize Spatial Memory Performance and Increase Neural Progenitor Cell Proliferation and Decrease Inflammation in the Aged Rat.
Acosta S, Jernberg J, Sanberg CD, Sanberg PR, Small BJ, Gemma C, Bickford PC.
1 Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair and Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine , USFHealth, Tampa, Florida.
Rejuvenation Res. 2010 Jun 29. [Epub ahead of print]

Abstract

Abstract The process of aging is linked to oxidative stress, microglial activation, and proinflammatory factors, which are known to decrease cell proliferation and limit neuroplasticity. These factors may lead the transition from normal aging to more severe cognitive dysfunction associated with neurodegenerative diseases. We have shown that natural compounds such as polyphenols from blueberry and green tea and amino acids like carnosine are high in antioxidant and antiinflammatory activity that decreases the damaging effects of reactive oxygen species (ROS), in the blood, brain, and other tissues of the body. Furthermore, we have shown that the combination of these nutrients (called NT-020) creates a synergistic effect that promotes the proliferation of stem cells in vitro and in vivo. In the current study, we examined the effects of NT-020 on neurogenesis and performance on a Morris water maze (MWM). Aged (20-month-old) male Fischer 344 rats were treated with 135.0 mg/kg per day (n = 13) of NT-020. Young (3-month-old) (n = 10) and aged (20-month-old) (n = 13) control male Fischer 344 rats were treated with water by oral gavage. All groups were treated for a period of 4 weeks. Although there was no difference in performance in the MWM when comparing all aged rats, when the data for aged impaired rats were compared, there was a significant difference between groups on the last day of training with the treatment group performing better than controls. Using the cell cycle-regulating protein (Ki67), doublecortin (DCX), and OX6 antibody markers, cell proliferation, neurogenesis, and microglial activation were estimated in the dentate gyrus (DG) of young and aged animals. Cell proliferation was also examined in the subventricular zone (SVZ). A decreased number of OX6 MHC II-positive cells, increased neurogenesis, and increased number of proliferating cells were found in rats treated with NT-020 in comparison with aged control rats. In sum, NT-020 may promote health, proliferation, and maintenance of neurons in the age animals and exert antiinflammatory actions that promote function in the aged stem cell niche.

PMID: 20586644 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20586644

This article explains what "NT-020" is: "NT-020, a proprietary formulation of blueberry, green tea, Vitamin D3, and carnosine"

Dietary supplementation exerts neuroprotective effects in ischemic stroke model.
Yasuhara T, Hara K, Maki M, Masuda T, Sanberg CD, Sanberg PR, Bickford PC, Borlongan CV.
Department of Neurology, Medical College of Georgia, Augusta, Georgia 30912, USA. cborlongan@mail.mcg.edu
Rejuvenation Res. 2008 Feb;11(1):201-14.

Abstract

This study examined whether dietary supplementation can be used to protect against ischemic stroke. Two groups of adult male Sprague-Dawley rats initially received NT-020, a proprietary formulation of blueberry, green tea, Vitamin D3, and carnosine (n = 8), or vehicle (n = 7). Dosing for NT-020 and vehicle consisted of daily oral administration (using a gavage) over a 2-week period. On day 14 following the last drug treatment, all animals underwent the stroke surgery using the transient 1-hour suture occlusion of middle cerebral artery (MCAo). To reveal the functional effects of NT-020, animals were subjected to established behavioral tests just prior to stroke surgery and again on day 14 post-stroke. ANOVA revealed significant treatment effects (p < 0.05), characterized by reductions of 11.8% and 24.4% in motor asymmetry and neurologic dysfunction, respectively, in NT-020-treated stroke animals compared to vehicle-treated stroke animals. Evaluation of cerebral infarction revealed a significant 75% decrement in mean glial scar area in the ischemic striatum of NT-020-treated stroke animals compared to that of vehicle-treated stroke animals (p < 0.0005). Quantitative analysis of subventricular zone's cell proliferative activity revealed at least a one-fold increment in the number of BrdU-positive cells in the NT-020-treated stroke brains compared to vehicle-treated stroke brains (p < 0.0005). Similarly, quantitative analysis of BrdU labeling in the ischemic striatal penumbra revealed at least a three-fold increase in the number of BrdU-positive cells in the NT-020-treated stroke brains compared to vehicle-treated stroke brains (p < 0.0001). In addition, widespread double labeling of cells with BrdU and doublecortin was detected in NT-020-treated stroke brains (intact side 17% and ischemic side 75%), which was significantly higher than those seen in vehicle-treated stroke brains (intact side 5% and ischemic side 13%) (p < 0.05). In contrast, only a small number of cells in NT-020-treated stroke brains double labeled with BrdU and GFAP (intact side 1% and ischemic side 2%), which was significantly lower than those vehicle-treated stroke brains (intact side 18% and ischemic side 35%) (p < 0.0001). Endogenous neurogenic factors were also significantly upregulated in the ischemic brains of NT-020-treated stroke animals. These data demonstrate the remarkable neuroprotective effects of NT-020 when given prior to stroke, possibly acting via its neurogenic potential.

PMID: 18260778 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/18260778

Here is one StemEnhance competitor called "
Stem Naturals" from BlueGreenFoods:

Stem Naturals increases adult stem cells and stem cell release for optimum health benefits. The Stem Naturals Stem cell Activator formula insures to create a better road to absorption by getting rid of toxins that block nutritional benefits in your body.  Stem Naturals Stem cell Activator formula will enable the effective use of nutrients in your body to the greatest degree possible.
http://www.bluegreenfoods.com/shop/proddetail.php?prod=Stem-Cell-Activator

Since these are supplements made from or extracted from AFA, I have to wonder, is there someone else selling it?  Is it available in an "unrefined" state.  For example, the supplement curcumin is the extract of the cury spice turmeric.  But, you would have to eat 18 times as much turmeric.  What I have been able to find about this product is that it is extracted from a blue-green algae called Aphanizomenon flos-aquae (AFA).  I checked some vitamin distributors and found that you can get AFA from several of them.  So instead of buying this product, I am going to look into trying whole AFA supplements.  I don't know how much or how often.

Apparently, Dr. Gabriel Cousens wrote a couple of articles about AFA back in the 80's and 90's:

http://www.shirleys-wellness-cafe.com/alzheimer.htm#cousens

Dr. Cousens is an interesting character. He's interested in exploring fringe ideas, to put it mildly. But, you never know where a good idea will come from. He seems like a classic California eccentric, although his Tree of Life Rejuvenation Center is in Patagonia, AZ.  But maybe despite all his... errr... unique studies, medically and scientifically, he might be OK.  I'll let you decide.
http://www.gabrielcousens.com/HOME/ABOUTUS/tabid/166/language/en-US/gabrielcousens.com/HOME/ABOUTUS/GABRIELCOUSENSMD/tabid/368/language/en-US/Default.aspx

The first scientific report published on AFA was by Gabriel Cousens, MD (1985), in the Journal of Orthomedicine on the treatment of Alzheimer's Disease.

Cousens G. Report of treatment of Alzheimer’s disease with Alphanae Klamathonmenon flos-aqua [sic].
Orthomedicine. Winter/Spring, 1985; 8(1):2.

Or perhaps...

Cousens, G., "Report of Treatment of Alzheimer's Disease with Alphanae Klamathomenon Flos-Aqua," Orthomedicine, 8:(1 & 2), 2000. cited by other.

M I C R O A L G A E
First & Finest Superfood

by Gabriel Cousens, M.D.

(Note: the following article appeared in Body Mind Spirit Magazine in May 1995...

Because of these brain-enhancing qualities, I became interested in exploring the effect of AFA on Alzheimer's disease. In my preliminary research, which was published in the Journal of Orthomolecular Medicine in the 1985 Winter / Spring Issue, I reported positive effects in both of two closely followed clients. Each had been diagnosed with Alzheimer's disease at highly respected university medical centers.

One client was a 66-year-old woman with a seven-year history of Alzheimer's disease who, after six months, showed a partial reversal of her disease. Her response to the AFA seemed to level off after six months and no further improvement was noted. The second case involved a 64-year-old lawyer who had suffered with Alzheimer's for three years. He seemed to be going downhill rapidly. After one month on high doses of AFA his degenerative process seemed to be arrested and he remained in this stabilized condition for three more years -- until his wife discovered that spirulina was cheaper than AFA and began to give him spirulina instead. Once off the AFA his condition began to deteriorate. The degeneration was slowed down when she put him back on the AFA. This unintended experiment highlights the difference in effect between AFA and spirulina.

These two cases do not prove that AFA cures Alzheimer's disease, but suggest it may be possible to temporarily halt the progression of the disease, to partially reverse or even help prevent it. It would take a comprehensive study to make any definitive statements about its effect on Alzheimer's and, as of yet, no study has been done...
http://www.algae-world.com/algae40.html

Here is a rather interesting, if not conspiratorial view of the FDA, B12, Folic Acid, and AFA posted to the newsgroup alt.fan.ronald-reagan back in 1998.  It is available through the Dejanews archives now owned by Google:

http://groups.google.com/group/alt.fan.ronald-reagan/browse_thread/thread/80e359359834a0c0/9cdfe89d14588f9?hl=en&q=aphanizomenon+alzheimer#09cdfe89d14588f9

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Known sources:

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Natural sources:


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References:

A Green Path to Healing & Rejuvenation
by Gabriel Cousens, M.D.
 
"AFA, among the more popular blue-green algae, seems to have a prana or energetic force for amplifying the function and energy of the mind and nervous system. It seems to activate neurotransmitter systems that help many people overcome depression; improve mental clarity, concentration and stamina, create a sense of joy, and enhance right-brain creativity. In my research of auricular acupuncture, the AFA specifically enhances pineal, pituitary, and hypothalamic function. Aside from hypothalamic glandular extracts, it is the only substance I know of that specifically enhances hypothalamic function. This is good news for vegetarians. I have seen it significantly help a few people with Alzheimer's disease and autism, as well as function as a brain-mind tonic for the general public."
http://www.algae-world.com/algae82.html



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Updated: July 2, 2012
Inception: July 2, 2012