The remainder of this file is divided into four parts:

I. What do people say about Super Blue Green Algae?

II. What is anatoxin-a?

III. Where does anatoxin-a come from?

IV. What does anatoxin-a do?

V. How can algae users protect against anatoxin-a?

PART I. What do people say about Super Blue Green Algae?

Here's a few quotes collected from both Cell Tech promotional literature and the FDA file on Cell Tech. There's remarkable agreement between these two sources on the effects of the algae. Capitalization added.

Quoting from _Personal_Experiences_with_Super_Blue_ _Green_Algae_ (Cell Tech promotional literature):

"On my initial consumption I felt better than ever, having incredible energy and elation. The excitement of it KEPT ME UP MOST OF THE NIGHT, yet that day at work I was without fatigue." -- C.H.

"Since I've been taking Super Blue Green Algae I experience very little jet-lag, sleep well, feel more alert than exhausted on a long flight. Fellow flight attendants are ASTOUNDED WITH MY ENERGY LEVEL!" -- L.L.D.

"When he was in the eighth grade, we decided to give him the Super Blue Green Algae. And we didn't tell anyone, because we didn't want there to be any bias. He took about six capsules, three Omega Sun and three Alpha Sun."

"At the end of two weeks three teachers called me and asked me, 'What are you doing different, Mrs. D? Is Ricky BACK ON A DRUG or something?' They said his work had dramatically improved. His attention span was better, his concentration had increased, he was responding and his school work was getting done and it was accurate." -- Mrs. D.

"We have begun to suggest Super Blue Green Algae to clients WITHDRAWING FROM COCAINE, with excellent results. It helps them through the depression and cravings connected with KICKING COCAINE." -- Robert Marrone, PhD, Sierra Center for the Healing Arts, Nevada City, CA.

Quoting from the official FDA Complaint/Injury Report on Cell Tech, October 31, 1995, filed by Lina Cicchetto, Consumer Complaint Coordinator:

"Product was supposed to be used in this manner: for the first week take digestive enzymes with spectrabiotics capsule 2 a day increasing weekly. For energy, after a week add to the initial capsules one capsule of the 'Blue Green Algae' capsule."

"She [the complainant] did this for a week then she added the algae, the first day she felt very energized, but did not sleep, next day she was so wired she COULD NOT SLEEP FOR A WEEK."

Quoting from the official FDA Complaint/Injury Report on Cell Tech, October 6, 1995, filed by Karen L. Robles, Consumer Safety Officer:

"Complainant began taking blue-green algae product and after 10 months felt no benefits. She stopped taking the product and has had an ENERGY IMBALANCE since that time. She has been suffering WITHDRAWL and energy imbalance."

Quoting from the official FDA Complaint/Injury Follow-Up Report on Cell Tech, November 24, 1995, filed by Susan R. Nelson, Supervisory Consumer Safety Officer:

"She [the complainant] stated she did not feel the benefits and quit taking the product (she was still taking the ------). She immediately had an ENERGY CRASH and had to stay in bed for a week, she couldn't get out of bed. ---------- stated she felt the algae had an ADDICTIVE effect on her and she has not felt the same since she quit the product."

Quoting from the official FDA Complaint/Injury Report on Cell Tech, April 4, 1995, filed by Cecilia Wolyniak, Division of Emergency and Enforcement Operations [quoting a complainant]:

"I believe Cell Tech's algae is a POWERFUL DRUG which must be regulated by the FDA. Further, the Oregon Department of Agriculture has cited Cell Tech for rat droppings in the storage areas and for a substantial number of insect parts in the product. It is difficult to believe that the FDA would permit a company like Cell Tech to sell what I believe to be a POTENT DRUG, under the guise of the label of 'food supplements,' under DSHEA of 1994 without oversight, monitoring, control and mandated safety testing. Simple logic would dictate that in addition to efficacy safety testing, the FDA would not permit a Merck, Squibb or a Genentech to allow insect particles in their products sanctioned by the FDA or permit rat droppings in their product storage areas."

PART II. What is anatoxin-a?

Quoting from _Toxicon_, volume 17, "Pharmacology of Anatoxin-a, Produced by the Freshwater Cyanophyte _Anabaena_flos-aquae_ NRC-44-1", by Carmichael, Biggs, and Peterson, 1979, page 229:

"Anatoxin-a (formerly called very fast death factor) is the term being used for the potent alkaloid neurotoxin produced by the freshwater cyanophyte _Anabaena_flos- aquae_ (Lyngb.) de Bre'b. clone number NRC-44-1."

"Its pharmacological properties have been investigated and compared with that of a synthetic anatoxin-a which was derived from L-cocaine."

"Anatoxin-a is a potent depolarizing neuromuscular blocking agent possessing both muscarinic and nicotinic activity."

Quoting from page 236:

"Structurally, anatoxin-a does not resemble decamethonium but instead is similar to the tropane alkaloids, specifically cocaine."

Quoting from _Molecular_Pharmacology_, volume 18, "Anatoxin-a: A Novel, Potent Agonist at the Nicotinic Receptor", by Spivak, Witkop, and Albuquerque, 1980, page 391:

"The potencies of six nicotinic agonists are compared (Table 2) for their ability to depolarize the frog's sartorius muscle by 10 mV. Interpolations from data published by other authors are cited to show that _anatoxin-a_is_the_most_potent_of_these_six_agonists_."

[Italics in the original.]

[An agonist is a molecule that binds to the same receptor. Agonists activate the receptor, while antagonists are non- activating and block the binding of the normal activating molecule, hence inhibit the action of the receptor.]

Quoting from _The_Journal_of_Pharmacology_and_ _Experimental_Therapeutics_, volume 259, number 1, "Nicotinic Pharmacology of Anatoxin Analogs. I. Side Chain Structure-Activity Relationships at Peripheral Agonist and Noncompetitive Antagonist Sites", by Swanson, Aronstam, Wonnacott, Rapoport, and Albuquerque, 1991, page 378:

"Anatoxin-a analogs with 12 different modifications of the 'acetyl' side chain moiety or a site directly influencing the conformation of this moiety were synthesized and evaluated pharmacologically. Fortunately, this extraordinary toxin has a semi-rigid homotropane skeletal structure that restricts the number of stable conformations."

Quoting from page 383:

"Several modifications of the side chain in anatoxin-a significantly changed the agonistic properties of the neurotoxins at the acetylcholinesterase receptor. No analog thus far tested _in_vitro_ was as potent as the parent compound anatoxin-a."

Quoting from _The_Journal_of_Pharmacology_and_ _Experimental_Therapeutics_, volume 259, number 1, "Nicotinic Pharmacology of Anatoxin Analogs. II. Side Chain Structure-Activity Relationships at Neuronal Nicotinic Ligand Binding Sites", by Wonnacott, Jackman, Swanson, Rapoport, and Albuquerque, 1991, pages 390-391:

"Such analysis assumes greater urgency with the realization that brain acetylcholinesterase receptors identified by high-affinity tritiated agonist binding are decreased in Alzheimer's disease (see Kellar and Wonnacott, 1990), and that nicotine treatment has given an encouraging result with respect to cognitive performance in Alzheimer patients (Sahakian _et_al_, 1989, 1990). Thus, centrally acting nicotinic agents could have an important therapeutic future in the symptomatic treatment of Alzheimer's disease (see Kellar and Wonnacott, 1990). Anatoxin-a is a useful core structure for such drug design because, as a secondary amine, it readily crosses the blood brain barrier."

Quoting from _Journal_of_Neurochemistry_, volume 60, number 6, "(+)-Anatoxin-a Is a Potent Agonist at Neuronal Nicotinic Acetylcholine Receptors", by Thomas, Stephens, Wilkie, Amar, Lunt, Whiting, Gallagher, Pereira, Alkondon, Albuquerque, and Wonnacott, 1993, page 2308:

"In these diverse preparations, (+)-anatoxin-a was between three and 50 times more potent than (-)-nicotine and about 20 times more potent than acetylcholine, making it the most efficacious nicotinic agonist thus far described."

And a surprise quote from page 2310:

"These studies were supported by grants from the R. J. Reynolds Tobacco Co. . . ."

PART III. Where does anatoxin-a come from?

Quoting from _Toxicon_, volume 17, "Pharmacology of Anatoxin-a, Produced by the Freshwater Cyanophyte _Anabaena_flos-aquae_ NRC-44-1", by Carmichael, Biggs, and Peterson, 1979, page 229:

"Toxic strains of freshwater cyanophytes have been implicated in animal poisonings for many years. _Anabaena_flos-aquae_, _Microcystis_aeruginosa_, and _Aphanizomenon_flos-aquae_ are the most common species responsible with the most recent reviews on the subject written by Moore (1977) and Gentile (1971)."

Quoting from _Journal_of_Applied_Phycology_, volume 5, number 6, "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.", by Rapala, Sivonen, Luukkainen, and Niemela, 1993, page 581:

"Anatoxin-a-concentration in cells of _Anabaena_ and _Aphanizomenon_-strains and in their growth media were studied in the laboratory in batch cultures at different temperatures, light fluxes, orthophosphate and nitrate concentrations and with different nitrogen sources for growth."

"The amount of toxin in the cells of the toxic strains was high, often exceeding 1% of their dry weight."

"The highest light flux studied did not limit the growth or decrease the level of the toxin in the cells of _Aphanizomenon_."

PART IV. What does anatoxin-a do?

Quoting from _Toxicon_, volume 30, number 8, "Cardio- Respiratory Changes and Mortality in the Conscious Rat Induced by (+)- and (+/-)-Anatoxin-a", by Adeyemo and Sire'n, 1992, page 904:

"Since adequate delivery of oxygen to the brain is of prime importance for central nervous system function, the observation that anatoxin-a-induced hypoxia was accompanied by severe and sometimes fatal acidosis suggests that brain hypoxia at the cellular level may result in the accumulation of lactate via anaerobic glycolysis producing acid-base stress, probable loss of reducing equivalents, and rapid depletion of high-energy phosphate compounds produced through oxidative phosphorylation."

Quoting from _Neuropharmacology_, volume 31, number 3, "Behavioural Effects of Anatoxin, a Potent Nicotinic Agonist, in Rats", by Stolerman, Albuquerque, and Garcha, 1992, page 314:

"Anatoxin differed from (-)-nicotine because it did not increase locomotor activity in rats made tolerant to the depressant effect of (-)-nicotine. It was unclear whether the tolerant rats were cross-tolerant to the locomotor depressant effect of (+)-anatoxin; the doses of (+)- anatoxin needed to decrease locomotor activity were larger in nicotine-tolerant than non-tolerant rats, but the basal level of activity was also lower. The partial, nicotine- like discriminative effect of (+)-anatoxin was notable because non-nicotinic drugs rarely mimic the discriminative effect of nicotine that is of central origin (Stolerman _et_al_, 1984)."

Quoting from _Journal_of_Analytical_Toxicology_, volume 12, "Analysis of Anatoxin-a by GC/ECD", by Stevens and Krieger, 1988, page 126:

"At present, the general method employed for the detection of anatoxin-a is a mouse bioassay. After lysis of cyanobacterial cells, up to 1 mL of sample water is injected i.p. into a mouse. Presence of anatoxin-a is inferred if the mouse expires within 10 minutes from respiratory arrest following violent convulsions. With a detection limit of about 5 micrograms toxin/20 gram mouse, the need for a sensitive, chemical analysis exists. The bioassay is inadequate for monitoring sublethal levels of anatoxin-a, . . ."

PART V. How can algae users protect against anatoxin-a?

Quoting from _Journal_of_Analytical_Toxicology_, volume 12, "Analysis of Anatoxin-a by GC/ECD", by Stevens and Krieger, 1988, page 126:

"Two methods for the detection of anatoxin-a in toxic samples have appeared in the literature--HPLC and GC/MS. Both methods involve cumbersome sample handling, and neither method is designed for trace quantitation of anatoxin-a on a routine basis. The HPLC method used UV detection, required a sample size of 100 mL, and employed 2 liquid-liquid extractions."

"Due to the low molar absorptivity of its alpha-beta unsaturated ketone, approximately 8500, the HPLC method lacks sufficient sensitivity necessary for trace anatoxin-a detection."

"Presently, a mouse bioassay is the general procedure used for testing the toxicity of a bloom--approximately 5 micrograms/ml anatoxin-a sensitivity. A method that is over three orders of magnitude more sensitive than that bioassay is described here. It is readily capable of detecting and quantitating sublethal levels of anatoxin-a."

Note that in the postings from Cell Tech in response to my files, they cite several specific tests they do on their algae. They perform the test for paralytic shellfish toxins, which happen to be toxins that _Aphanizomenon_ can also produce. They test for microcystins, which are toxins that a contaminating algae in Klamath Lake is known to produce. They test for anatoxin-a(s), which is a different molecule from anatoxin-a that has a similar name, because both were originally discovered in an algae called _Anabaena_. To my knowledge, nobody has ever found anatoxin-a(s) in _Aphanizomenon_. But they do not routinely test for anatoxin-a with the Stevens and Krieger protocol. They claim to use the bioassay and HPLC methods to detect anatoxin-a, but as the quotes above indicate, these methods are inadequate for detecting sublethal (but possibly psycho- active) levels of anatoxin-a. It seems to me like their testing program was delibrately designed to test for every possible toxin except one: anatoxin-a. Could it be that taking the anatoxin-a out of the algae would be like taking the nicotine out of tobacco?

They say they've had some tests performed using the Stevens and Krieger protocol, but they do not say when these tests were performed, on how many batches, who performed the tests, nor have they released the lab reports.

I've heard rumors Cell Tech had some typical manufacturing batches of the algae tested using that test. I've heard these rumors for over half a year, and I've been wondering why they didn't make the test results public. Could it be that they actually found some level of anatoxin-a?

I'd certainly be the first to say that the Stevens and Krieger test can detect levels of anatoxin-a that are below those which could harm anybody or have a pharmacological effect. So just finding some level is not proof that anatoxin-a is responsible for the feelings of "energy" reported by SBGA users. But if they found _zero_ anatoxin-a, why did they not report that data when they first obtained it? And if the level is not zero, then just exactly what is it?

What level is below the level which would be psychoactive? I can't cite any firm numbers for this, but the potency of anatoxin-a has been compared against nicotine. Anatoxin-a is reported to be up to 50 times more powerful than nicotine. One Carlton cigarette (one of the weakest cigarettes you can buy) delivers about 100 micrograms of nicotine, according to the label on the package. I would say that if one gram dry weight of the algae contains less than 2 micrograms of anatoxin-a, then anatoxin-a might not be responsible for the "energy" reported by SBGA users.

2 micrograms is 2000 nanograms. If the level is a factor of ten below that, i.e. 200 nanograms, then I would say the "energy" probably does not come from anatoxin-a. Note that the Stevens and Krieger test has a detection threshold around 5 nanograms, so it's way more sensitive than it needs to be to find these levels.

I'll offer the following deal. If the tests were performed by a reputable lab (rumor has it that Carmichael did the tests -- can't get more reputable than that!), and if Cell Tech makes the lab reports on these tests available, and if the levels are below 200 nanograms/gram dry weight, I'll stop posting THE ANATOXIN-A PRIMER. Doesn't that sound like a great deal? Every SBGA distributor should get on the phone to their upline asking Cell Tech to do this!