Journey Into Better Health

StemEnhance

FDA's CAM Draft Guidance Frequently Asked Questions

OTHER FREQUENTLY ASKED TOPICS
-Response to Mr. Stephen Barrett of MLM Watch.org
and the National Council Against Health Fraud
-The Whole Story About Microcystin and AFA
-Aphanizomenon flos-aquae Review of The LiteratureRegarding Neurotoxicity
-Quality and Safety of Klamath Lake Blue-Green Algae

1. What is a stem cell?

A stem cell is a cell that has the ability to duplicate itself endlessly and to become cells of virtually any organ and tissue of the body. Embryonic stem cells are cells extracted from the blastula, the very early embryo, that have an exceptional ability to duplicate in vitro, that is in a test tube, and to become cells of almost any tissue. Adult stem cells are cells found in an organism after birth. Until very recently, it was believed that adult stem cells could only become blood cells, bone and connective tissue. But recent development over the past 5 years have revealed that adult stem cells have capabilities
similar to embryonic stem cells.

2. What is the Stem Cell Theory of Renewal?

The Stem Cell Theory of Renewal proposes that stem cells are naturally released by the bone marrow and travel via the bloodstream toward tissues to promote the body's natural process of renewal. When an organ is subjected to a process that requires renewal, such as the natural aging process, this organ releases compounds that trigger the release of stem cells from the bone marrow. The organ also releases compounds that attracts stem cells to this organ. The released stem cells then follow the concentration gradient of these compounds and leave the blood circulation to migrate to the organ where they proliferate and differentiate into cells of this organ, supporting the natural process of renewal.

3. Why do we hear much in the news about embryonic stem cells and very little about adult stem cells?

The first human embryonic stem cells were grown in vitro, in a petri dish, in the mid 1990s. Rapidly, scientists were
successful at growing them for many generations and to trigger their differentiation into virtually any kind of cells, i.e. brain cells, heart cells, liver cells, bone cells, pancreatic cells, etc. When scientists tried growing adult stem cells, the endeavor was met with less success, as adult stem cells were difficult to grow in vitro for more than a few generations. This led to the idea that embryonic stem cells have more potential than adult stem cells. In addition, the ethical concerns linked
to the use of embryonic stem cells have led to a disproportionate representation of embryonic stem cells in the media.

But recent developments over the past 2-3 years have established that adult stem cells have capabilities comparable to embryonic stem cells in the human body, not in the test tube. Many studies have indicated that simply releasing stem cells from the bone marrow can help support the body's natural process for renewal of tissues and organs.

4. What is the effect of StemEnhance?

StemEnhance is a blend of two compounds extracted from the widely consumed aquatic botanical Aphanizomenon
flos-aquae (AFA). One extract, which contains 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 into tissues.

5. What is the science behind StemEnhance?

The effect of StemEnhance on stem cells was tested in a triple-blind study. In brief, volunteers rested for one hour before the first blood sample, which established the baseline level in the number of circulating stem cells. After the first blood samples, volunteers were
given StemEnhance or placebo. Thereafter, blood samples were taken at 30, 60 and 120 minutes after taking the consumables. The number of circulating stem cells was quantified byanalyzing the blood samples using Fluorescence-Activated Cell Sorting (FACS). Consumption of StemEnhance triggered a significant 25% increase in the number of circulating stem cells.

6. What is the recommended dose?

One gram of StemEnhance triggers a significant 25-35% increase in the number of circulating stem cells. The effect lasts for a few hours. The recommended dosage is therefore 2 capsules once or twice day, at least 6 hours apart.

7. Can StemEnhance deplete the bone marrow? Do we have a finite number of stem cells?

No, StemEnhance will not deplete the bone marrow. The bone marrow constantly produces stem cells for the entire life of an individual. Stem cells released by the bone marrow are responsible for the constant renewal of red blood cells and lymphocytes (immune cells).

A 25-30% increase in the number of circulating stem cells is well within physiological range and does not constitute stress on the bone marrow environment. The amount of active bone marrow amounts to about 2,600 g (5.7 lbs), with about 1.5 trillion marrow cells. A 25-30% increase in the number of circulating stem cells triggered by the consumption of 1 gram of StemEnhance corresponds to approximately 3 million cells, which is a small portion of the stem cells present in the bone marrow. Stem cells that do not reach any tissue or become blood cells return to the bone marrow.

8. What happened to stem cells if they do not reach a tissue?

Stem cells released from the bone marrow that do not reach a tissue simply home back to the bone marrow after some
time.

9. Can stem cells lead to aberrations such as cancer?

Only embryonic stem cells have been associated with the development of aberrant growth. Stem cells present in
specialized tissues such as the intestinal mucosa may also play a role in the development of aberrant growth.
But stem cells released from the bone have not been associated with such problems.

10. Why has StemTech HealthSciences elected to use the Network Marketing distribution channel?

The Stem Cell Theory of Renewal constitutes a new paradigm in health sciences. Likewise, StemEnhance is the first
product in a novel category of revolutionary products called stem cells enhancers. Stem cell enhancers are product that supports stem cell functions in the body. Given the novel nature of both the concept and the product, a significant effort of education is required to help people become aware of this new technology. The power of networking offers a unique opportunity to generate awareness and educate people about this new paradigm. Furthermore, the MLM channel offers unique opportunities for people to develop home-based businesses and create greater financial freedom.

11. Why may StemEnhance be contraindicated for people on anticoagulant therapy?

One gram of StemEnhance contains roughly half of the recommended daily allowance in vitamin K. Vitamin K is an
essential nutrient playing an important role in the process of blood coagulation. Hence, doctors often tell people to avoid vitamin K while being on anticoagulant therapy. This being said, it is not so much the presence of vitamin K in the diet as much as the consistency in the daily intake. Therefore, the best approach is to discuss with your doctor your desire to take StemEnhance, that it contains vitamin K, and the anticoagulant prescription can be adjusted through careful monitoring of your condition by your doctor.

12. Can Stem Enhance be taken with other drugs?

There is a possible interaction with antidepressant medications, as StemEnhance contains phenylethylamine (PEA), a compound naturally produced by the brain that affect dopamine and norepinephrine in the brain. PEA is known for its effect on mood elevation and mental energy. Interactions with antidepressant medications have not been reported, but the possibility exists. People should consult their doctor before taking StemEnhance if they are on antidepressant medication.

There are no other known contraindications.

13. Can Stem Enhance be taken by children?

The ability of stem cells to be released by the bone marrow and the quality of the stem cells released by the bone marrow both appears to decrease with age. Therefore, one might conclude that children and infants have a very effective stem cell system and do not need stem cell support. Nevertheless, we have received very compelling testimonials suggesting that StemEnhance could bring significant benefits to young children.

StemEnhance is made of two extracts from the cyanophyta Aphanizomenon flos-aquae (AFA), which has been consumed by
children for more than two decades with a good history of safety.

14. How does an increase in the number of circulating stem cells lead to optimal health?

Circulating stem cells can reach various organs and become cells of that organ, helping such organ regain and maintain
optimal health. Recent studies have suggested that the number of circulating stem cells is a key factor; the higher the number of circulating stem cells the greater is the ability of the body at healing itself.

15. What is the optimum way of taking StemEnhance capsules?
StemEnhance can be taken with or without food, though some people at times experience some heaviness when taken on
an empty stomach. The same experience has been reported when taken with an acidic juice like orange juice. Otherwise, StemEnhance can be taken with any fruit or vegetable juice, or with water.

In our studies, StemEnhance was always taken in the morning. However, it is quite possible that StemEnhance might bring greater benefits when taken before sleep, as the body tends to regenerate better during sleep. This being said, this remains to be studied. At this point, with the data available, the best way to take StemEnhance is to take 2 capsules once or twice a day, in the morning or morning and evening.

16. Is StemEnhance FDA approved?

No. FDA does not approve dietary supplements in the same way that FDA approves some drugs and medical devices.
Nonetheless, FDA does regulate product quality, product safety, and product claims, and has authority to remove products from the market that are not safe or that make claims that are not substantiated by scientific evidence.

17. Is StemEnhance truly natural? Organic? Non-genetically modified? Farmed?

StemEnhance is made of two extracts from the aquatic botanicals Aphanizomenon flos-aquae (AFA). AFA grows naturally in a pristine lake of Southern Oregon, it is therefore wildcrafted, not farmed or manipulated in anyway, hence no genetic modification. StemEnhance is produced by an Organic certified facility and is certified Organic.

18. Are there any synthetic ingredients in StemEnhance? If so, what?

StemEnhance is made of 100% natural AFA extracts.

19. Is StemEnhance actually patented, or has the company only applied for a patent?

One patent has been issued on StemEnhance and another one has been filed. The issued patent is a Use Patent that
pertains to the use of AFA for supporting stem cell physiology. The second patent is a Composition Patent that pertains to the specific components in AFA responsible stem cell support.

20. How is StemEnhance different from whole AFA?

Whole AFA has been used for more than two decades with a very good track record of safety and health benefits. Whole
AFA has been used as a natural anti-inflammatory product, to support the immune system, and to improve mental clarity
and mental energy. Over the past few years StemTech's scientific team has isolated and identified the various components in AFA responsible for the various health benefits of AFA. In brief, AFA has been found to contain 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 most recently an L-selectin ligand responsible for supporting the release of stem cells from the bone marrow.

StemEnhance is a 5:1 concentrate of AFA that concentrates the four compounds listed above. It is specifically designed and developed to support stem cell physiology, but it also concentrates other compounds unique to AFA, bringing unique support for the whole body.

21. What are other ways of increasing your stem cell blood level?

Due to the novelty of the concept of supporting the release of one's own stem cells, very little scientific work has been done so far to identify compounds or conditions that increase the release of stem cells from the bone marrow.
So far, StemEnhance is the only natural compound shown to support the release of stem cells from the bone marrow.

22. What are the ingredients?

The ingredients are listed in the Supplement Fact box of the label, as stipulated by the Dietary Supplement Health and Education Act. One serving is obtained with 2 capsules, totaling 1 gram of cyanophyta extracts. StemEnhance is made of only two ingredients that are extracted from the same plant, Aphanizomenon flos-aquae.

Labeling laws require listing any nutrient found in an amount superior to 2% of the daily recommendation. Carotenoids and proteins are found in significant amount in StemEnhance. Therefore, carotenoids and proteins that are naturally present in StemEnhance are listed on the label. Carotenoids are listed as vitamin A because they are measured as retinal
equivalent.

Response to Mr. Stephen Barrett of MLM Watch.org
and the National Council Against Health Fraud

Recently, people conducting an Internet search on stem cell enhancer's were surprised to find an article by Stephen
Barrett already raising doubts about StemEnhance and stem cell enhancers. We welcome this opportunity to provide you
with further information on StemEnhance.

Barrett provides a relatively good background history of StemEnhance and StemTech HealthSciences (STHS). However he
makes an inaccurate rapprochement between STHS and Cell Tech. STHS nor Desert Lake Technologies has NEVER been
involved in any lawsuit about false claims. The work done by STHS and DLT is based on science, it is completely
independent from Cell Tech, and all of our claims are solidly backed by science.

Barrett also claims that blue-green algae based products might contain dangerous toxins. (See below for reports on
microcystin and neurotoxicity) There is no excuse at this point in time, nearly a decade after the industry has developed a stringent quality control program, to still repeat such irrelevant allegations. Whereas infection of beef by E.coli is still responsible for more than 20,000 intoxications and nearly 500 deaths every year, whereas aflatoxin in corn, peanuts, milk products, spices and other foodstuff have been responsible for several deaths, and whereas shellfish toxins are still responsible for several deaths every year, blue-green algae has been linked to no ill effect. Like any other food ingredient, if potential contaminants like heavy metals, pesticides, and shellfish toxins are present in quantity below levels established as safe, then the product is deemed safe. Stating that blue-green algae may be dangerous is akin to stating
that eating a shrimp cocktail or a hamburger at your favorite restaurant is dangerous. Such a statement reflects a lack of scientific background and knowledge, or deceptive intent.

Barrett states that before taking any product, it is advisable to know whether it has been proven safe and effective for its intended purpose(s), and that with respect to StemEnhance, the following questions would have to be answered.

Frequently Asked Questions

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


1. What evidence shows that taking StemEnhance will improve anyone's health?

Numerous studies performed by various scientific teams throughout the world, including the National Institute of Health[1] have clearly established that the higher the levels of circulating stem cells the better the ability of the body to maintain optimal health. A recent publication in the New England Journal of Medicine[2] reported that the level of stem cells in the blood was one of the best indicators of cardiovascular health. Elevating the number of stem cells in the blood has been shown to improve health in many ways. [3-6] StemEnhance supports the release of stem cells from the bone marrow and increases the number of circulating stem cells by 25-30%, which is bound to assist the body in maintaining optimal health.

As Mr. Barrett must know, given his claimed experience with the FDA, that we cannot make any health claims linked to
StemEnhance since it is a dietary supplement and not a drug. Our claims are limited to structure and function claims, which is what we have solidly documented. StemEnhance supports the natural release of stem cells from the bone marrow, thereby assisting the body in maintaining optimal health. We would be delighted to publish the single patient outcomes we have documented, but they could be construed as inferred health claims. Nevertheless, clinical studies are currently in progress involving specific organs and system to further document the mechanics of stem cell physiology, and these studies will be eventually published.

2. Has any study shown that people improved their health as a result of taking it?

Numerous empirical reports and testimonials testify to the health benefits of taking StemEnhance. Many companies have
been shut down by the FDA because of inferred health claims linked to documentation of improvements with various
diseases. We intend to maintain our message clearly within the boundaries of the Dietary Supplement Health and
Education Act, and let StemEnhance speaks for itself. We would be delighted to provide Mr. Barrett with a few bottles of
StemEnhance so he can see the benefits on his own health.

3. What evidence shows that StemEnhance is safe for long-term use?

AFA, the raw ingredient from which StemEnhance is derived, has been on the marketplace for more than two decades with
a very good track record of safety. A safety study in mice determined that consumption of the equivalent of up to 2,000 AFA capsules daily led to no health problems at all. In fact, the authors claimed that the mice receiving the highest dose of AFA were less aggressive and looked healthier. StemEnhance is a 5:1 concentrate of AFA, and just like 5:1 concentrates of echinacea or grape seed or ginkgo or wheat grass juice that are as safe as the whole plant they are derived from, StemEnhance is as safe as whole AFA. StemEnhance is to whole AFA what carrot juice is to a whole carrot.

The question may also refer to the safety of increasing the number of circulating stem cells everyday by 25-30%. Here
also the safety is unquestionable. The normal range for the number of circulating stem cells is between 1.2 and 5.0 stem cells per L of blood. An increase of 30% in the number of circulating stem cells would at most mean an increase of 1.5 cells per L, which is well within normal physiological range. Looking at this from a different angle, Krause et al. [7] reported that one single stem cell was enough to reconstitute the entire hematopoietic (red blood cell) and immune systems. If one single stem cell can do this, then the billions of stem cells left in the bone marrow after taking StemEnhance can maintain a healthy and strong bone marrow.

4. How can users be certain that long-term use will not cause abnormal tissue growth?

The release of stem cells from the bone marrow and their migration to tissues is a natural process that happens everyday.
StemEnhance simply supports that natural process and tips the balance toward health everyday. StemEnhance does not do
anything that the body does not already do everyday. So far, no instances of cancer or any similar problem have ever been observed when using in vivo natural release of stem cells from the bone marrow. Abnormal cellular growth has only been seen when manipulating stem cells in test tubes.

5. For whom is the product advisable?

Since StemEnhance supports the natural release of stem cells from the bone marrow, which is turn travel throughout the body to maintain the health of various organs and tissues. StemEnhance is the optimal daily support for the maintenance of optimal health. It is for everyone interested in giving their body an extra boost toward daily renewal of cells throughout the body. It is for anyone interested in supporting his or her body's natural renewal system.

6. Who should not take it?

StemEnhance naturally contains a significant amount of vitamin K. Therefore, anyone taking anticoagulant medication should consult their doctor in order to adjust the medication, if necessary. StemEnhance could also be contraindicated for anyone having a disease of the bone marrow, though this is solely speculative and is not based on any observation of ill effect.

AFA contains phenylethylamine (PEA), known as the "molecule of love" or the "molecule of joy". PEA is a natural
compound made by the brain whenever one feels content, happy. Deficiency in PEA has been linked to problems of
concentration and low mood, and oral intake of PEA has been shown to improve these conditions. StemEnhance concentrates PEA at about 5mg/g. PEA is responsible for the immediate feeling of well-being that one experiences after
taking StemEnhance. Because of the effect of PEA in the brain, StemEnhance could be contraindicated for people suffering from severe manic depression.

Finally, Barrett states that A few studies's most of them done in laboratory animals have shown that circulating stem cells from bone marrow can develop into a few other types of mature cells. As far as I know, however, no study has
demonstrated that increasing the number of circulating cells is safe or makes people healthier. This is certainly the most eloquent expression of Barrett's lack of expertise in this field.

Anyone interested to see if there are onlya few studies's showing that circulating stem cells can develop into a few other cell types's, can simply do a search on Medline to see the thousands of article on that topic. Or simply refer to the study of Krause[7] in which bone marrow stem cells were seen to become functional cells of the skin, liver, colon, intestine, stomach, esophagus, kidney and lung. Bone marrow stem cells have also been documented to become brain cells,[8] heart cells,[1] muscle cells,[9] pancreatic cells[10] virtually any cell type in the body. As to the second statement that to Barrett's knowledge no study has demonstrated that increasing the number of circulating cells makes people healthier, one only needs to refer to the studies by Orlic at the NIH[1] and that of Werner et al.[2] Barrett could have done a simple search at the NIH library with the key words "circulating stem cells" "healing" (PubMed) and he could have avoided misleading people as he did.

I believe it is important for the sake of ethics and public integrity to end this discussion by putting these comments from Stephen Barrett, as well as all other comments by him, into a bigger context. Barrett is a retired psychiatrist who has not had many positive comments about dietary supplements and over the years have waged a little vendetta against anything that comes through an Network Marketing. He would probably be against peanut butter if they were sold through and MLM.

His attacks against natural approaches such as homeopathy and herbal medicine constituted a rather eloquent display of his ignorance.
He created the so-called National Council Against Health Fraud, which ironically is itself rather fraudulent and misleading, as it does not represent any objective and expert council, it does not represent any official national organization, and it provides rather biased information. Barrett claims to have several links with the FDA and a great expertise in FDA matter.
We will let Judge Fromholz of the California Superior Court Case shed some light on Mr. Barrett. As stated by the Judge, Barrett's motives appear to be more linked to personal financial gain than generous public education.

Below is an excerpt from Judges decision rendered against NCAHF 12/17/01 by Judge Framholz in California Superior
Court. You can read the complete transcript, "A Judges View of the Quackbusters"

Dr. Barrett was offered on several issues by the Plaintiff, but the Court found that there was substantial overlap on the issues that he and Dr. Sampson were asked to address. Thus, in order to avoid duplicative or cumulative evidence (see Cal. Evidence Code §§ 352, 411, 723), Dr. Barrett's testimony was limited by the Court to the sole issue of FDA treatment of homeopathic drugs. The relevancy of this issue was questionable at best, since the Plaintiff had previously asserted that its case did not depend on or seek to establish any violation of federal food and drug laws or regulations. Nevertheless, Plaintiff elicited testimony from Dr. Barrett on his experience with the FDA as it relates to regulation of homeopathic drugs.

Dr. Barrett was a psychiatrist who retired in or about 1993, at which point he contends he allowed his medical license to lapse. Like Dr. Sampson, he has no formal training in homeopathic medicine or drugs, although he claims to have read and written extensively on homeopathy and other forms of alternative medicine. Dr. Barrett's claim to expertise on FDA issues arises from his conversations with FDA agents, his review of professional literature on the subject and certain
continuing education activities.

As for his credential as an expert on FDA regulation of homeopathic drugs, the Court finds that Dr. Barrett lacks sufficient qualifications in this area. Expertise in FDA regulation suggests a knowledge of how the agency enforces federal statutes and the agency's own regulations. Dr. Barrett's purported legal and regulatory knowledge is not apparent. He is not a lawyer, although he claims he attended several semesters of correspondence law school. While Dr. Barrett appears to have had several past conversations with FDA representatives, these appear to have been sporadic, mainly at his own instigation,
and principally for the purpose of gathering information for his various articles and Internet web-sites. He has never testified before any governmental panel or agency on issues relating to FDA regulation of drugs. Presumably his
professional continuing education experiences are outdated given that he has not had a current medical license in over
seven years. For these reasons, there is no sound basis on which to consider Dr. Barrett qualified as an expert on the
issues he was offered to address. Moreover, there was no real focus to his testimony with respect to any of the issues in this case associated with Defendants' products.

Furthermore, the Court finds that both Dr. Sampson and Dr. Barrett are biased heavily in favor of the Plaintiff and thus the weight to be accorded their testimony is slight in any event. Both are long-time board members of the Plaintiff; Dr. Barrett has served as its Chairman. Both participated in an application to the U.S. FDA during the early 1990s designed to restrict the sale of most homeopathic drugs. Dr. Sampson's university course presents what is effectively a one-sided, critical view of alternative medicine. Dr. Barrett's heavy activities in lecturing and writing about alternative medicine similarly are focused on the eradication of the practices about which he opines. Both witnesses' fees, as Dr. Barrett testified, are paid from a fund established by Plaintiff NCAHF from the proceeds of suits such as the case at bar. Based on this fact alone, the Court may infer that Dr. Barrett and Sampson are more likely to receive fees for testifying on behalf of NCAHF in future cases if the Plaintiff prevails in the instant action and thereby wins funds to enrich the litigation fund described by Dr. Barrett.

It is apparent, therefore, that both men have a direct, personal financial interest in the outcome of this litigation. Based on all of these factors, Dr. Sampson and Dr. Barrett can be described as zealous advocates of the Plaintiff's position, and therefore not neutral or dispassionate witnesses or experts. In light of these affiliations and their orientation, it can fairly
be said that Drs. Barrett and Sampson are themselves the client, and therefore their testimony should be accorded little, if any, credibility on that basis as well.

References

[1] Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine DM, Leri A. & Piero Anversa.
(2001) Mobilized bone marrow cells repair the infracted heart, improving function and survival. PNAS
98(18):10344–10349.

[2] Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G. (2005) Circulating endothelial
progenitor cells and cardiovascular outcomes. N Engl J Med. 8;353(10):999-1007.

[3] Bozlar M, Aslan B, Kalaci A, Baktiroglu L, Yanat AN, Tasci A. (2005) Effects of human granulocyte-colony stimulating
factor on fracture healing in rats. Saudi Med J. 26(8):1250-4.

[4] Kong D, Melo LG, Gnecchi M, Zhang L, Mostoslavsky G, Liew CC, Pratt RE, Dzau VJ. (2004) Cytokine-induced
mobilization of circulating endothelial progenitor cells enhances repair of injured arteries. Circulation. 110(14):2039-46.

[5] Eroglu E, Agalar F, Altuntas I, Eroglu F. (2004) Effects of granulocyte-colony stimulating factor on wound healing in a mouse model of burn trauma. Tohoku J Exp Med. 204(1):11-6.

[6] Tomoda H, Aoki N. Bone marrow stimulation and left ventricular function in acute myocardial infarction. Clin Cardiol.
2003 Oct;26(10):455-7.

[7] Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis SJ. (2001) Multi-organ,
multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105:369-77.

[8] Eglitis MA and Mezey VA. (1997) Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc. Natl. Acad. Sci. USA Vol. 94, pp. 4080,4085.

[9] Camargo FD, Green R, Capetenaki Y, Jackson KA, and Goodell MA. (2003) Single hematopoietic stem cells generate
skeletal muscle through myeloid intermediates. Nature 9(12):1520-27.

[10] Ianus A, Holz GG, Theise ND, and Hussain MA. (2003) In vivo derivation of glucosecompetent cells from bone marrow
without evidence of cell fusion. J. Clin. Invest. 111:843-850.

The Whole Story About Microcystin and AFA
Much has been said and written about microcystin as a possible contaminant of the cyanophyta Aphanizomenon flos-aquae (AFA). Everything seen on the media and read on the Internet spurred from an event that took place in the summer of 1996, in which I was one of the main protagonists. At the time, the magnitude of the misinformation was such that we elected not to respond, thinking that such misinformation could not last. I can tell now that it was ill-advised, and I decided
to tell the whole story.

AFA has been on the marketplace as an exceptional dietary supplement for more than two decades. During this time, not
one incident remotely linked to microcystin has been reported or to any other toxin as a matter of fact. But the media has established another perceived reality for AFA, under a unique set of circumstances.

In 1996, I was Director of Research and Development of a marketing company centered around the sale of AFA. Soon after my arrival in 1995, I implemented a testing procedure for a then little-known toxin with the collaboration of Dr. Wayne Carmichael of Wright State University. The toxin was microcystin, which is produced by a type of blue-green algae called Microcystis. Since Microcystis is seen at times in Klamath Lake during some parts of the summer and since a new assay had been developed to measure microcystin, we decided to add this testing to our quality control program. In order to have records as complete as possible we tested samples backing as far as 1992. As expected, microcystin was present in small amounts that presented no health concern.

However, in the summer of 1996 we observed a bloom of Microcystis that was somewhat larger than the previous years.
After much discussion with several experts we elected to be pro-active with the situation and to trigger an education
campaign. Similar to the story with aflatoxin in peanuts and corn, we decided to educate the local authorities and to work toward the development of safe limits to ensure quality and safety. We invited officials at the Oregon Health Division (OHD) to visit our facilities and to tell them about microcystin and our Quality Control program.
It was the first time they were hearing about microcystin. We showed them the test, the inventory of product on hold, caught by an efficient Quality control program; we showed them everything.

We thought we had done our duty and acted responsibly; we were expecting a response from OHD that would honor the
approach we had taken. To our surprise, soon after the officials at OHD published an article mentioning that microcystin was a dangerous toxin, that more than 60 people had died in Brazil from microcystin toxicity.
What they failed to mention was that this incident was linked to intravenous exposure through dialysis to about
25 gallons of water contaminated with microcystin.
There is a world of difference between intravenous and oral exposures.
Just think bout having a teaspoon of peanut butter injected in your vein.

In the same article they mentioned that product containing as much as 20 ppm of microcystin had been harvested, though
they failed to mention that this product had been caught by an effective Quality Control program and never reached any
consumer. We were appalled. The moment we tried to defend our position we became the unconscionable corporate entity
trying to make money by intoxicating people. Nothing could have been further from the truth. While a safe limit of 20 ppb had been established for aflatoxin, levels as high as 300 ppb have been tolerated at times, like in 1988, when a drought threatened farmers in the Midwest. Salmonella is present in about 0.02% of the eggs consumed by American, which amounts to a few thousand real exposures everyday. Contamination of ground beef by E. coli is responsible for an estimated 20,000 hospitalization and nearly 500 deaths every year. While all of these are tolerated, OHD triggered an unprecedented misleading bad press for a product that had no history of ill effect.

Officials at OHD went as far as publishing an appalling paper in the scientific literature reporting that in spite of a ruling limiting the amount of microcystin in AFA at 1 ppm, 85 of the 87 samples taken from the marketplace contained a level of microcystin superior to 1 ppm.
As with their previous releases, they failed to mention an important piece of information.

The ruling was passed on October 17, 1997. Between the summer of 1996 and the date of the ruling, the industry had
adopted the safe limit proposed by two prominent scientists, Dr. Wayne Carmichael, expert in toxic cyanobacteria at Wright State University, and Dr. Gary Flamm, former Head Toxicologist at the FDA in Washington, who both proposed a safe level of 5 ppm. These testimonials are on records at the Oregon Department of Agriculture (ODA). The samples tested by OHD were taken from the marketplace in the months following the ruling of 1 ppm. However, all the samples came from product released on the marketplace prior to the ruling, respecting the interim level of 5 ppm proposed by the experts. So while the industry was playing by the rules and respecting experts opinion, OHD once again acted deceptively concluding that the industry ignored the ruling. The situation was like one day changing the speed limit on a street and then accusing someone of having driven too fast the day before. The intent to deceive was obvious for those knowing the situation in details.

Supported by experts we proposed to have a moratorium at 5 ppm for 2 years while we would pay for studies showing the
safety of low levels of microcystin in AFA. The study that OHD relied upon for their safety assessment consisted of mice gavaged daily with pure toxin dissolved in water.
The very process of gavaging a mouse leads to significant liver injury.
In that study, at times control groups showed greater toxicity than the group receiving the highest level of toxin. The study was obviously flawed. Beside, using pure toxin was inappropriate. For example, AFA contains significant levels of silymarin, a bioflavanoid known to provided 100% protection against microcystin. To establish the safety of microcystin as a contaminant of AFA, we have to test microcystin in AFA. OHD refused any suggestion.

Later on, someone close to the one person leading this whole vendetta at OHD, Duncan Gilroy, told me that no reasonable argument could change OHD's position because Duncan Gilroy did not like blue-green algae and had the clear intention of bringing down this industry. Even after the ruling of 1 ppm, Gilroy kept telling consumer that no level of microcystin was safe and people should avoid consuming from blue-green algae. In any industry if a product is below the level considered safe, the product is deemed pure and safe for consumption, like corn and peanuts with aflatoxin, and beef with E. coli.

The facts

The blue-green algae harvested from Klamath lake and currently sold on the market is more than 99% Aphanizomenon
flos-aquae. This blue-green alga from Klamath Lake is absolutely non-toxic, as demonstrated by many years of extensive testing. During a few weeks in the summer, Microsystis, a co-occurring blue-green alga capable of producing the toxin microcystin, is found as a minor constituent of the Klamath Lake phytoplankton community. This phenomenon is not recent and Microcystis has always been present in very small amounts in Klamath Lake.
Despite its presence, Microsystis is not a problem, since Desert Lake Technologies (DLT) has developed a method to separate this alga from Aphanizomenon
flos-aquae.

In 1995, Dr. Wayne Carmichael from Wright State University and Dr. Don Anderson from Woodshole Oceanographic
Institute became consultants for a member of the Klamath Lake Algae industry, on the specific issue of algal toxicity.
During the summer of 1996 a substantial bloom of Microcystis was unexpectedly observed that started in early July and continued into the third week of September.
In collaboration with Dr. Jake Kann, Dr. Wayne Carmichael and Dr. Don Anderson, the situation was brought to the public's attention, because of the industry's commitment to public safety and public education, which led to the Oregon Health Division's awareness of the situation.

Because of the existence of only a few proposed guidelines based on single studies and the uncertainties surrounding
these studies, an unrestricted grant was given to the University of Illinois for the completion of a comprehensive risk assessment, reviewing more than 300 scientific articles, aimed at accurately evaluating the risk associated with microcystin as a possible contaminant of blue-green algae products. This risk assessment determined that 10 g/g was considered a safe level. A similar safe level (5 g/g) was later confirmed by a risk assessment performed by Dr. Gary Flamm, former head toxicologist at the FDA in Washington, DC. This safe level of 5 g/g was also supported by Dr. Wayne Carmichael in a
written testimonial.

Despite the written opinions of many experts and the significant amount of data indicating that levels of 5 g/g and even 10 g/g were safe for human consumption, even children, the Oregon Department of Agriculture decided to pass a regulation establishing 1 g/g as the maximum acceptable concentration (MAC). The actual safe level determined by animal studies was between 2,500 and 6,000 g of microcystin per day. To add a margin of safety, this safe level was further divided by a factor of 1,000. The adopted safe level of 1 g/g is therefore 1,000 times lower than level established as safe in animal studies, ensuring complete safety for children. Microcystin is indeed a liver toxin, however, it is completely safe at the levels currently found in blue-green algae products. Liver damage only occurs at levels that exceeds 10,000 times the adopted safe level of 1 g/g. One would have to eat more than 5,000 capsules per day to reach such levels.

The industry nonetheless welcomed the regulation and went immediately into compliance. During the entire process and
after the adoption of the regulation the relationship between ODA and the blue-green algae industry has been one of collaboration.

One of the unresolved elements of this regulatory process was the development of a validated assay to quantify
microcystin. It was believed that such an assay could be developed in the year following the adoption of the regulation.

However, collaboration between ODA and FDA in Washington State, as well as with independent universities and
institutions, has failed to produce a validated test for the precise measurement of microcystin at low levels. Nevertheless, the tests currently utilized that have been developed and refined over the past 5 years, an enzyme linked immunosorbent assay (ELISA) and a protein phosphatase inhibition assay (PPIA), are precise enough to monitor compliance, even though levels found in a same sample analyzed on different occasions, or by different laboratories, can at times show significant
variations.

In conclusion, the blue-green algae industry has been extremely pro-active with the problem of the presence of
Microcystis in Klamath Lake. Members of the Klamath Lake Algae industry have worked with the Oregon Department of Agriculture to raise the regulated level to 5 g/g.
However, DLT's position has been to fully integrate the regulatory level of 1 g/g, and to develop ways to reduce microcystin content.

As stated before, DLT has developed and implemented a method to separate Microcystis for Aphanizomenon flos-aquae. Lots of AFA harvested since 2000 all tested at less than 1 g/g.

Aphanizomenon flos-aquae

Review Of The Literature Regarding Neurotoxicity
Aphanizomenon flos-aquae (Aph. flos-aquae) is a filamentous blue-green algal species harvested each summer from
Upper Klamath Lake in Klamath Falls, Oregon. Aph. flos-aquae has been sold as a nutritional food supplement for nearly 20 years. It is known to be rich in certain vitamins (B12, carotenoids, K) and in trace minerals. The nutritional benefits of Aph. flos-aquae have been appreciated by over a million consumers, many of whom reported increased energy levels, heightened mental clarity, improved memory and recall, and an overall feeling of well-being.

Aph. flos-aquae from Upper Klamath Lake

To appreciate Aph. flos-aquae from Klamath Lake, it is important to consider the unique ecosystem in which this alga blooms. Upper Klamath Lake, which covers approximately 325 km2, has the greatest surface area of any natural water body in Oregon (Gearheart et al. 1995). Numerous springs charged with water filtered through miles of nutrient-rich volcanic soils on the flanks of the Cascade mountains (Gearheart et al. 1995), and six major tributaries, contribute 90% of the annual inflow to the lake (1,527,600 mean acre-feet (1929-1993); Gearheart et al. 1995). Overall, Upper Klamath Lake is described as a very productive eutrophic lake that is marked by high levels of available nutrients and plant life.
It is this wealth of nutrients that allows Aph. flos-aquae to grow in such abundance in the wild. Upper Klamath Lake is one of only a few ecosystems which supports the recurrent growth of Aph. flos-aquae in such abundance.

Upper Klamath Lake has sometimes been referred to as polluted because of the lake's incredible bounty of Aph.
flos-aquae. The most observable influence of this blue green algae is the change in the chemical properties of the water around the blooming algal masses, namely dissolved oxygen, pH and ammonia. Given summer conditions and a large
algal bloom, water chemistry can change drastically and these parameters can reach levels that can directly impact fish species (Monda and Saiki, 1993). Fish will congregate near inflow areas of better water quality, yet their density and stressed condition renders them susceptible to outbreaks of disease and die-offs. In Upper Klamath Lake such fish kills (1971, 1986, 1995) are generally attributed to outbreaks of Columnaris disease (Logan and Markle, 1993). These outbreaks have been common in fish hatcheries under crowded, high temperature conditions (Piper et al. 1982). Such impact on the survival of fish has led people unaware of this natural chemistry to state that Klamath Lake is polluted.
Various testing for pesticides, petro-chemicals and other contaminants over the past 10 years failed to reveal the presence of any such contaminants.

Aph. flos-aquae and the issue of neurotoxicity

A few reports of neurotoxicity in the scientific literature have raised unwarranted concern. Aside from these reports, nearly ten years of regular testing (more than 300 samples tested) has failed to reveal the presence of any neurotoxins. In the late 1990's two lawsuits were filed against companies harvesting from Klamath Lake for neurotoxicity. Both cases were dismissed after considerable effort to detect neurotoxins proved unsuccessful. Finally, a study recently published used genetic technologies to determine that the previous reports of neurotoxicity associated with Aph. flos aquae had misidentified the algal species and the toxic algal samples were not Aph. flos aquae but a species of Anabaena.
Below is a brief and more detailed account of the evolution of the scientific data regarding the neurotoxicity of Aph. flos aquae.

Klamath Lake

The first article to report toxicity of Aph. flos aquae summarized a 1960 US Department of Health, Education and Welfare seminar in which authors Phinney and Peek (1961) refer to a toxic algal bloom that occurred in Upper Klamath Lake in the late 1950's. A sample of this algal bloom was sent to Dr. Paul Gorham, then at the National Research Council, Ottawa, Canada, for toxicological analysis. Although Phinney and Peek reported:
"no concrete evidence was obtained as to the effect of this toxin on the biota of the Lake and River, but experiments with mice proved that ingestion of the algal material was quickly lethal and intraperitoneal injection of the aqueous extract almost instantaneous in causing death",
Gorham determined that the sample was not pure Aph. flos-aquae, but actually consisted of equal parts of Aph. flos-aquae and Microcystis - an algae known to produce microcystins. Gorham concluded that the toxicity came not from the Aph. flos-aquae, but from the Microcystis (Gorham, 1964; Carmichael and Gorham, 1980; Gorham, personal communication to W.W.C., 1995).

The second article concerning Klamath Lake was a preliminary summary of a toxicity test on Upper Klamath Lake Aph. flos-aquae published by Gentile (1971) in a review article on blue-green and green algal toxins. A mouse assay (n=1) was performed on a colony isolate of Aph. flos-aquae cultured for a short period of time in a laboratory. Signs of poisoning in the mouse were reported as similar to that of a Kezar Lake, New Hampshire (see below) Aph. flos-aquae sample later shown to produce a toxin with similarities to saxitoxin and its derivatives.

In both articles, several elements did cast significant uncertainty concerning this possible neurotoxicity of Upper Klamath Lake Aph. flos-aquae. These include:
1) lack of taxonomic verification of Aph. flos-aquae as the dominant alga in the tested culture;
2) lack of a complete mouse bioassay which would have established the minimum lethal dose, LD50 and toxicity compared to known saxitoxin standards; and
3) lack of a confirmation of toxicity by other laboratories working with these neurotoxins.
For these reasons, it could not be concluded that Aph. flos-aquae from Upper Klamath Lake produced a neurotoxin. Asquoted by Gentile (personal communication to W.W.C., March 27, 1996), This anecdotal toxicity test on Upper KlamathLake Aph. flos-aquae should be rigorously restudied before it can be concluded that the alga produces a toxin. Periodictoxicity tests in the 1980's plus frequent regular testing since 1991 have failed to reveal any neurotoxins in Upper KlamathLake Aph. flos-aquae (Carmichael et al., 2000).

Aph. flos-aquae samples from other locations

In spite of the complete absence of neurotoxicity as tested numerous times using HPLC and mouse bioassay, doubts
regarding the possible neurotoxicity of Klamath Lake Aph. flos-aquae persisted because of the discovery of three samples of Aph. flos-aquae found elsewhere
(USA and Finland) that contained neurotoxicity.

Sawyer et al. (1968) and Gentile and Maloney (1969) reported toxicity of an atypical non-colony forming Aph. flos-aquae that killed fish and laboratory mice. This Aph. flos-aquae came from Kezar Lake in New Hampshire.

More recently, Rapala et al. (1993) reported toxicity of Aph. flos-aquae isolated from water blooms in Finland. These studies establish that Aph. flos-aquae is toxic only in some geographical locations. This study also demonstrated that it was not possible, under the
experimental conditions, to manipulate a non-toxic strain of Aph. flos-aquae to become toxic.

At this point in time, the general consensus among scientists was that some strains of Aph. flos-aquae were capable of producing neurotoxins but most strains, include the Klamath Lake strain, were non-toxic.

One aspect that caught the attention of several scientists was the mention in the aforementioned articles that the toxic samples of Aph. flos-aquae were atypical non-colony forming Aph. flos-aquae. In other words, the toxic strains that were originally identified and classified as Aph. flos-aquae were not typical of Aph. flos-aquae and the original identification could have been inaccurate. Indeed, the boundary between Aph. flos-aquae and some Anabaena species is very unclear and misidentification of the algal species can be problematic. Anabaena spp. is known to produce various kinds of neurotoxins.
Recent developments in genetics have provided the tools to determine, using genetic similarities, whether the toxic strains of Aph. flos-aquae are the same species as the strain showed to be non-toxic. Recently, Li et al. (2000) have shown that all the toxic strains of Aph. flos-aquae are genetically dissimilar to the non-toxic strains and most likely belong to the Anabaena genera.

Court Cases

It is interesting to briefly discuss two instances in which lawsuits were filed around the issue of neurotoxicity of Klamath Lake Aph. flos-aquae.

In the first one a man, Mr. Fineman, claimed that consumption of Aph. flos-aquae triggered neuropathy. The case revealed that Mr. Fineman had been suffering from diabetes since early childhood and had had many episodes of developing neuropathy. After two years of contracting with various laboratories throughout the world to detect and identify a neurotoxin in Aph. flos-aquae, Mr. Fineman had to withdraw the suit because of lack of evidence. The court obliged Mr. Fineman to published the following statement:
"I, Samuel Fineman, brought a lawsuit against Cell Tech and the Kollmans because I thought I had been harmed by some
substance in Cell Tech's products. Testing and investigation (including testing for neurotoxins) did not confirm the presence of any such substance. Accordingly, I have withdrawn my lawsuit in its entirety."

In a second case, the aforementioned company Cell Tech filed a lawsuit against an individual, Mark Thorson, who had relentlessly published over the Internet that Aph. flos-aquae from Klamath Lake contained a neurotoxin similar to cocaine and dangerous to consumers. Once again, after considerable effort to prove his allegations, Mr. Thorson lost his case. He was also asked to published the following statement over the Internet:
During the last several years, I have from time to time posted to this and other newsgroups a file of information called "An Anatoxin-a Primer." I now retract the statements made in the Anatoxin-a Primer.
The Anatoxin-a Primer implied that Super Blue Green Algae from Klamath Lake, produced by Cell Tech, contains
anatoxin-a (a neurotoxin I characterized as addictive), and that Cell Tech deliberately avoids testing for this toxin because anatoxin-a is responsible for the effects reported by SBGA users. I have since been advised that Cell Tech conducts regular tests that would disclose anatoxin-a, and that this toxin has never been found in Super Blue Green Algae. I had no basis for the suggestions I made in the Anatoxin-a Primer, and I hereby retract it in full.

These two cases are interesting as they both relied on the explicit demonstration that Aph. flos-aquae from Klamath Lake contained a neurotoxin. In both cases, many laboratories throughout the world with the capability and the expertise to detect and quantify neurotoxins were contracted to find neurotoxins in Aph. flos-aquae from Klamath Lake, with no success.

Summary

In summary, the few instances of reports of neurotoxicity of Aph. flos-aquae pertained not to Aph. flos-aquae but to species believed to be Anabaena spp. All samples shown to be Aph. flos-aquae by PCR technology (genetics) were all reported to be non-toxic. In addition, two significant legal suits failed to detect the presence of any neurotoxin in Aph. flos-aquae from Upper Klamath Lake.
Taken altogether, the available data demonstrate the non-toxicity of Aph. flos-aquae from Upper Klamath Lake.


REFERENCES

Carmichael, W.W., Drapeau, C., and Anderson, D.M. (2000) Harvesting of Aphanizomenon flos-aquae Ralfs ex Born. & Flah.
Var. flos-aquae (Cyanobacteria) from Klamath Lake for human dietary use, J. App. Phyco., vol. 12, pp. 585-595.

Carmichael, W.W., and P.R. Gorham. (1980) Freshwater cyanophyte toxins, In: Algae Biomass, Elsevier, New York, pp.
437-448.

Gearheart, R.A., J.K Anderson, M.G. Forbes, M. Osburn, and D. Oros. (1995) Watershed strategies for improving water
quality in Upper Klamath Lake, Oregon. Humboldt State University, Environmental Resources Engineering Department. 3
Volumes.

Gentile, J.H., and T.E. Maloney. (1969) Toxicity and environmental requirements of a strain of Aphanizomenon flos aquae
(L.) Ralfs, Can. J. Microbiol., vol. 15 (2), pp. 165-173.

Gentile, J.H. (1971) Blue green and green algal toxins. In: Microbial Toxins, Vol. 7, Academic Press, New York, pp. 27-67.

Gorham, P.R. (1964) Toxic Algae. In: Algae and Man, Plenum Press, New York, pp. 307-306.

Logan, D.J., and D.F. Markle (1993) Fish faunal survey of Agency Lake and northern Upper Klamath Lake, Oregon. In
Environmental research in the Klamath Basin, Oregon -1992 Annual Report. S.G. Campbell (ed.) p. 341.

Monda, D.P. and M.K. Saiki. (1993) Tolerance of Juvenile Lost River and Shortnose suckers to high pH, ammonia
concentration, and temperature, and to low dissolved oxygen concentration. In Environmental research in the Klamath
Basin, Oregon - 1992 Annual Report. S.G. Campbell (ed.) p. 341.

Piper, R.G, I.B. McElwain, L.E. Orme, J.P. McCraren, L.G. Fowler, and J.R. Leonard. (1982) Fish Hatchery Management. U.S. Department of the Interior, Fish and Wildlife Service. Washington D.C. p. 517.

Phinney, H.K. and Peek, C.A. (1961) Klamath Lake, an instance of natural enrichment.
In Transactions of the seminar on Algae and Metropolitan Wastes. U.S. Public Health Service, pp. 22-27.

Rapala, J., Sivonen, K., Luukkainen, R., and S.I. Niemela. (1993) Anatoxin-a concentration in Anabaena and
Aphanizomenon under different environmental conditions and comparison of growth by toxic and non-toxic Anabaena
strains - a laboratory study, J. Applied Phycol., vol. 5, pp. 581-591.

Li, R., Carmichael, W.W., Liu, Y., and Watanabe, M.M. (2000) Taxonomic re-evaluation of Aphanizomenon flos-aquae NH-5 based on morphological and 16 rRNA gene sequences, Hydrobiologica, vol. 438, pp. 99-105.

Sawyer, P.J., Gentile J.H., and J.J. Sasner. (1968) Demonstration of a toxin from Aphanizomenon flos-aquae (L.) Ralfs,
Can. J. Microbiol., vol. 14, pp. 1199-1204.

QUALITY AND SAFETY OF
KLAMATH LAKE BLUE-GREEN ALGAE

Overview

Klamath Lake Algae is a nutritional food supplement which is harvested each summer from Upper Klamath Lake in Klamath
Falls, Oregon and consists almost exclusively of the filamentous blue-green algal species Aphanizomenon flos-aquae. Aph. flos-aquae is a nutrient dense food rich in vitamins, minerals, essential amino acids, and proteins. The nutritional benefits of Klamath Lake Algae mostly reported are increased energy levels, heightened mental clarity, improved memory and recall, relief of inflammatory conditions and an overall feeling of well-being.

Klamath Lake Algae from Upper Klamath Lake is absolutely non-toxic. However, like many other agricultural products,
Klamath Lake Algae may contain naturally occurring compounds, microorganisms or by-products of human activity that need to be monitored and controlled. Each batch (lot) of Klamath Lake Algae is subjected to a battery of scientific tests to ensure that the algae consistently meets the highest standards of safety and purity. As a result of these tests, Klamath Lake Algae is one of the purest and safest foods available.

Klamath Lake Algae in Upper Klamath Lake

To appreciate Klamath Lake Algae, one first should consider the unique ecosystem in which the algae blooms.
Upper Klamath Lake, which covers approximately 125 square miles, has the greatest surface area of any natural water body in Oregon (Gearheart et al. 1995). Numerous springs charged with water filtered through miles of nutrient-rich volcanic soils on the flanks of the Cascade mountains (Gearheart et al. 1995), and six major tributaries, contribute 90% of the annual inflow to the lake (1,527,600 mean acre-feet (1929-1993); Gearheart et al. 1995). Overall, Upper Klamath Lake is described as a very productive eutrophic lake that is marked by high levels of available nutrients and plant life. It is this wealth of nutrients that allows Aph. flos-aquae to grow in such abundance in the wild. Upper Klamath Lake is one of only a few ecosystems which supports the recurrent growth of Aph. flos-aquae in such abundance.

Historically, Upper Klamath Lake was a highly productive (eutrophic) and diverse ecosystem due to a naturally high inflow of nutrients (Gearheart et al. 1995). Though the term eutrophic is often associated with adverse water quality conditions, in reality, a body of water may be ecologically healthy and eutrophic. In their 1967 report, Miller and Tash described a nutrient-rich sediment layer many feet deep in Upper Klamath Lake. They reported that the principal nutrients in Upper Klamath Lake were supplied through natural geological processes in quantities sufficient to maintain dense algal blooms, however they did not include nutrient loading which resulted from either local or upper watershed non-point sources (mostly poor forestry and agricultural land management; Gearheart et al. 1995). Current information indicates that human activities have increased nutrient loading to the lake over historical background levels (Bortleson and Fretwell 1993; Gearheart et al. 1995). However, much of the current debate centers on the effect of additional nutrients on an already productive environment. Both internal and external nutrient loading can influence nutrient concentrations in the
lake (Bortleson and Fretwell 1993) and probably the composition of the planktonic community, however the paucity of long-term scientific data makes it difficult to determine actual causes. Kaffka et al. (1995) remarked that phosphorous concentrations in available studies were above levels that many limnologists think are limiting to algal growth, and concluded that anthropogenic (human) influences in the Basin were of little consequence compared to natural enrichment processes. However, during periods of intense algal blooms in Upper Klamath Lake, dissolved phosphorus concentrations are reduced to levels which are known to be limiting (Gearheart et al. 1995).

Other biologists (Gearheart et al. 1995;
Bortleson and Fretwell 1993; Kann and Smith 1993; Miller and Tash 1967) have documented increases in productivity and algal growth over the past century. Bortleson and Fretwell (1993) noted that these increases in productivity were detrimental to fish populations and that such productive systems have the potential to increase the magnitude of algal blooms, furthering the detriments to fish. To counteract these potential changes, most Klamath Basin biologists have expressed support for efforts to restore natural conditions through wetland restoration and initiation of appropriate land management practices in the watershed.

Since agricultural and forestry managed land border the Upper Klamath Lake watershed (although more than 70% of the
watershed is in federal ownership), runoff from these activities does enter Upper Klamath Lake. Though questions about the effect of nutrient loading (sometimes technically referred to as non-point source pollution) on lake water quality and lake productivity exist, this does not affect the safety and purity of Aph. flos aquae for human consumption. Although highly charged emotionally and politically, the word polluted, in the Upper Klamath Lake ecosystem, describes a condition in which concentrations of dissolved nutrients (phosphorus and nitrogen) have increased to higher than historic levels.
These nutrients have subsequently impacted the aquatic community of the lake by enhancing algal growth and by affecting related chemical properties (dissolved oxygen, pH, ammonia, etc.) of the lake water. When Upper Klamath Lake is said to be polluted, the term usually refers to the amount of nutrients present, their influence on algal growth, and the impact of this algal growth on lake's aquatic life. Upper Klamath Lake water is practically free of contaminants and man made toxicological pollutants. The nutrients which enter Upper Klamath Lake are the same materials which are referred to as fertilizer when found in topsoil (nitrogen and phosphorus compounds). While not recommended for direct human consumption, they are absolutely necessary components of a growing medium for all plant matter, including algae in Upper Klamath Lake. Upper Klamath Lake is for the algae what a rich soil is for any vegetable.

One of the reasons Upper Klamath Lake is sometimes referred to as polluted or believed to be polluted, regardless of its nutrient source, is because of the lake's incredible bounty of Aph. flos-aquae. Such abundant algal growth is customarily associated with pollution. The most observable influence of abundant algal growth is the change in the chemical properties of the water around the blooming algal masses. In the presence of sunlight, algae utilize carbon dioxide and produce oxygen as a by-product of photosynthesis (the conversion of light energy to chemical energy). Due to the limited solubility of oxygen in water at high temperatures, relatively little oxygen dissolves in the water and the remainder is released into the atmosphere. During the night, however, algae do not photosynthesize but instead consume oxygen and decrease the
amount of dissolved oxygen in the water. When the algal bloom declines and cells begin to die, nightly oxygen demand of the remaining algae, combined with oxygen demand of decaying material in the water, can reduce oxygen levels in Upper Klamath Lake to levels which affect the health of aquatic animals. The fluctuation in carbon dioxide in turn drives changes in lake pH which may directly or indirectly influence the health of fish in the area. Given summer conditions and a large algal bloom, water chemistry can change drastically and dissolved oxygen, pH and ammonia may reach levels which can directly impact fish species (Monda and Saiki, 1993). If fish are not directly affected, they may be stressed by environmental conditions and their resistance to commonly rejected parasites and diseases reduced. These fish will then congregate in and/or near inflow areas of better water quality, yet their density and stressed condition renders them susceptible to outbreaks of disease and die-offs. In Upper Klamath Lake such fish kills (1971, 1986, 1995) are generally attributed to outbreaks of Columnaris disease (Logan and Markle, 1993).
These outbreaks have been common in fish hatcheries under crowded, high temperature conditions (Piper et al. 1982), and are caused by a common bacteria which specifically affects fish. Under given circumstances, Columnaris, which is normally under control, may take an explosive course and cause catastrophic losses in one or two days after first appearing (Piper et al. 1982).

While the algal species that is now indirectly associated with these fish kills in Upper Klamath Lake is Aph. flos-aquae, this type of reaction to high temperatures and photosynthetically changed water conditions is not restricted to this time or location or to this species. The first reported fish kill in Upper Klamath Lake was reported by Gilbert in June of 1894 (Logan and Markle 1993). While this mortality may have been partly a result of post spawning stress, it is also likely that hot calm
conditions and the resulting algal blooms could have degraded water conditions and contributed to this occurrence. While this implies that algal blooms in Upper Klamath Lake are natural and occurred before any large-scale anthropogenic activity around the lake, reported fish kills seem to have increased in frequency through time. Summer fish kills have also occurred in numerous nutrient rich lakes in Canada (Barica 1975). In an effort to assist recovery of diminished native Upper Klamath Lake fish stocks, extensive cooperative work between local environmental agencies has been initiated to
explore and enact actions which will ultimately ameliorate conditions which result in these fish kills.

REFERENCES
Barica, J. 1975. Summerkill risk in prairie ponds and possibilities of its prediction. Journal Fisheries Research Board of
Canada. Vol 32, pp. 1283-1288.

Bortleson G.C., and M.O. Fretwell. 1993. A review of possible causes of nutrient enrichment and decline of endangered sucker populations in the Upper Klamath Lake, Oregon. U.S.G.S. Water-Resources Investigations Report 93-4087, p. 24.

Gearheart, R.A., J.K Anderson, M.G. Forbes, M. Osburn, and D. Oros. 1995. Watershed strategies for improving water
quality in Upper Klamath Lake, Oregon. Humboldt State University, Environmental Resources Engineering Department. 3
Volumes.

Kaffka, S.R., Lu, T.X., and H.L. Carlson. 1995. An assessment of the effects of agriculture on water quality in the Tule lake Region of California. Research Progress Report 108. Univ. Of California. p. 85.

Kann, J. and V.H. Smith. 1993. Chlorophyll as a predictor of elevated pH in a hypertrophic Lake: Estimating the probability of exceeding critical values for fish success.

Klamath Tribes Research Report: KT-93-02. The Klamath Tribes, Chiloquin, Oregon. p. 22.
Logan, D.J., and D.F. Markle 1993. Fish faunal survey of Agency Lake and northern Upper Klamath Lake, Oregon. In
Environmental research in the Klamath Basin, Oregon -1992 Annual Report. S.G. Campbell (ed.) p. 341.

Matsunaga, S., Moore, R.E., Niernezura, W.P., and W.W. Carmichael. 1989. Anatoxin-a(s) a potent anticholinesterase from Anabaena flos-aquae, J. Amer. Chem. Soc., vol. 111, pp. 8021-8023.

Miller, W.F, and J.C. Tash. 1967. Interim report: Upper Klamath Lake Studies, Oregon, Federal Water Pollution Control Administration. p. 37.

Monda, D.P. and M.K. Saiki. 1993. Tolerance of Juvenile Lost River and Shortnose suckers to high pH, ammonia
concentration, and temperature, and to low dissolved oxygen concentration. In Environmental research in the Klamath
Basin, Oregon - 1992 Annual Report. S.G. Campbell (ed.) p. 341.

Oshima, Y., Sugino, K., and T. Yasumoto. 1989. Latest advances in HPLC analysis of paralytic shellfish toxins. In:
Mycotoxins and phycotoxins, Natoris, S., Hashimoto, K., and Ueno, T. [Eds], Elsevier, New York, pp. 319-326.

Piper, R.G, I.B. McElwain, L.E. Orme, J.P. McCraren, L.G. Fowler, and J.R. Leonard. 1982. Fish Hatchery Management. U.S. Department of the Interior, Fish and Wildlife Service. Washington D.C. p. 517.

Q&A ON FDA'S DRAFT GUIDANCE
COMPLIMENTARY AND ALTERNATIVE MEDICINE PRODUCTS AND THEIR
REGULATION BY THE FOOD AND DRUG ADMINISTRATION

http://www.fda.gov/OHRMS/DOCKETS/98fr/06d-0480-gld0001.pdf
Q: Does this Draft Guidance change how FDA regulates dietary supplements such as StemEnhance?

A: No The Draft Guidance provides FDA's proposed definition of CAM products (Complimentary and Alternative Medicine Products) and explains how these products, depending on how they are labeled and marketed and for what specific intended uses, will fall into existing FDA regulatory categories such as drugs,& biologics, devices or foods (which include dietary supplements).

Q: Can dietary supplement products still be marketed with
structure/function claims such as supports the natural release of adult stem cells?

A: Yes, The Draft Guidance has no impact on legal structure/function claims for foods or dietary supplements, and does not change how products making such claims will be regulated.

Q: If individual distributors or the manufacturer make oral or written claims for a dietary supplement that the product will help prevent or treat a disease, how will the product be regulated according to the Draft Guidance?

A: As an illegal drug -- Disease prevention or treatment claims, such as curing or preventing cancer, diabetes, arthritis or other disease, would cause FDA to regulate the dietary supplement as an illegal drug, with the exception that if there is an FDA-approved health claim, disease prevention claims might be legal. Disease treatment claims for dietary supplements were illegal before the issuance of the Draft Guidance and continue to be illegal. Claims to decrease risk or prevent disease should not be made in the context of the sale of dietary supplements without first confirming that such claims are legal as a result of an FDA-approved health claim.