The Healing Power of Rainforest Plants

The Cat's Claw TOA-POA Controversy

By Leslie Taylor

There have been numerous changes in cat's claw products (and their marketing ) in the last five years, and some of it has been rather confusing to many consumers and professional health care providers. Heck, it was even confusing to me--so I had to spread out all the files and journal articles again and review them. I'd like to take some time to solidify the research and the facts as I see them. I've also uploaded the complete technical data report on cat's claw (that usually sells for $20.00) in PDF format so that readers can review all this compiled research for themselves.

It is well documented that the chemical composition of cat's claw (so far) includes 17 different alkaloids, quinovic acid glycosides, tannins, flavonoids, sterol fractions, and other compounds. Cat's claw contains a group of oxindole alkaloids with documented biological activities. The vine bark and the root bark have been consistently, independently assayed to contain the following oxindole alkaloids:

The Oxindole Alkaloids

Pentacyclic oxindole alkaloids (POAs) Tetracyclic oxindole alkaloids (TOAs)
Pteropodine Rhynchophylline
Isopteropodine Isorhynchophylline
Speciophylline Corynoxeine
Uncarine F Isocorynoxeine

The first chemical analysis of Uncaria tomentosa was published in 1974. The leaves and stems of U. tomentosa were found to contain the tetracyclic alkaloids rhynchophylline, isorhynchophylline, mitraphylline, isomitraphylline, dihydrocorynantheine, and the indole alkaloids hirsutine and hirsuteine (Hemingway and Phillipson, 1974; Phillipson et al., 1978). The presence of the pentacyclic alkaloids pteropodine, isopteropodine, speciophylline, uncarine F, and isomitraphylline in the vine bark of uña de gato (in both U. tomentosa and U. guianensis) was reported (Montenegro de Matta et al., 1976) early on as well. Researchers working on the alkaloid fractions ever since have documented the TOA alkaloids rhynochophylline and its isomer, isorhynophylline, in the bark and the root. They always have been part of cat's claw's naturally-occurring chemicals.

The four U.S. patents filed by Keplinger/Immodal from 1989-1998 indicate that all their samples contained these two TOA alkaloids . . . in fact, they cited the POA alkaloid mitraphylline as having no immune stimulating effect, but the TOA alkaloid isorhynchophylline did stimulate phagocytosis, saying,
"Phagocytosis was enhanced by pteropodine, isomitraphylline and isorhynchophylline. The strongest stimulation was observed with isopteropodine whereas mitraphylline and rhynchophylline had no effect."

In three of the Keplinger/Immodal patents on these alkaloids, it states: "Tetra- and pentacyclic oxindole alkaloids, in particular the alloisopteropodine, isomer A, a pentacyclic oxindole alkaloid, are suitable for the unspecific stimulation of the immunologic system, which has been proved by a substantial percental phagocytosis increase in the granulocytic test. . . " Nowhere in any of that research was it documented that rhynchophylline or the other TOA alkaloids actually lowered immune function; rather, they've been reported to be among the active alkaloids that stimulate the immune system.

Surely if they were testing these TOA alkaloids for their increase in phagocytosis they would have noticed and reported that they actually inhibited phagocytosis instead of raised it? Instead, they tested these TOA alkaloids and stated that they had no effect on phagocytosis--with the exception of isorhynchophylline, a TOA, which actually stimulated it. All of the independent research published in five countries that followed, with researchers testing vine and root decoctions and/or whole oxindole alkaloid extracts (all of which would have contained the naturally occurring TOA and POA alkaloids), continued to confirm an in vitro and in vivo immune stimulation effect within the same average percentages.

The average breakdown of the alkaloids as confirmed by independent laboratories testing cat's claw vine bark is represented in the table below. It has never been proven scientifically that the root or the root bark contains more alkaloids than the vine bark. In fact, independent lab analysis over the years shows the vine bark contains an equal or greater percentage of alkaloids than the root and/or root bark.

Raintree vine bark (Industrial Labs, Inc.) Another U.S. label vine bark tablet (assayed by Austrians) Another U.S. Label vine bark capsule (assayed by Austrians) Austrian made TOA-free root extract (their assay)
Pteropodine 0.2% 0.224% 0.142% 0.558%
Isopteropodine 0.29% 0.225% 0.132% 0.145%
Speciophylline 0.13% 0.008% 0.005% 0.341%
Uncarine 0.03% 0.013% 0.009% 0.097%
Mitraphylline 0.6% 0.052% 0.075% 0.206%
Isomitraphylline 0.3% 0.127% 0.105% 0.031%
Total POA Alkaloids 1.55% .649% .468% 1.38%
Rhynchophylline 0.07% 0.097% .186% --
Isorhynchophylline 0.04% 0.040% 0.081% --
Corynoxeine -- 0.004% 0.018% --
Isocorynoxeine -- 0.001% 0.007% --
Total TOA Alkaloids 0.11% .135% .292% --
Total Alkaloids 1.66% .784% .760 1.38%

If commercially sold samples of cat's claw are testing higher today in TOAs there is a good reason for it, and it's not that the plant is somehow mutating or changing its chemical makeup! The fact is, market demand for cat's claw has increased dramatically in the past five years, and a huge amount of cat's claw has been harvested out of the Peruvian Amazon and exported out of Peru (in the last 5-8 years). Brazilian harvesters have entered the market in the last five and are exporting as well. There are two species of plants harvested and exported as "cat's claw." The "original" cat's claw species, Uncaria tomentosa , is getting harder for wild harvesters to find because of over-harvesting and sustained market demand. The other species that grows in the Amazon is Uncaria guianensis. This species is closely related to tomentosa and looks very similar (even growing in the forest). It is literally indistinguishable from tomentosa after it has been harvested (unless subjected to chemical analysis). If one can see the claws or hooks on the vines (sometimes they are 30 meters above ground in the canopy and obscured by other vegetation), it's easy to tell which is tomentosa and which is guianensis-- the hook shapes are different. The leaves of the tomentosa species are also more hairy than those of guianensis (but, again, the leaves can be many meters up, and it's the lower vine that is cut off in harvesting). (See photographs of both species) Tomentosa generally grows at higher elevations than guianensis does--which means more difficult terrain to navigate and from which to harvest.. Guianensis grows at lower elevations--at river level--which is much easier to find, get to, harvest, and transport. Independent phytochemical analysis shows, however, that both plants contain most all of the same phytochemicals (and alkaloids)--just in different ratios.

Local people, peasants, farmers, and others harvest cat's claw in Peru to sell to middlemen or brokers along the river for cash. Cash is hard to come by in the remote Amazon. When the vine is harvested in the jungle, the outer bark with these distinguishing hooks are stripped off and left in the forest. More often, the lower part of the vine is simply cut away from the upper vine (which contains the distinguishing "hooks"). The upper vine is discarded in the top of the canopy where it's wound around everything. The inner bark is then stripped out and bundled for sale along the river. By the time it ends up in Lima, there is no way to tell if the inner bark is tomentosa or guianensis--it looks identical. It's my guess that, today, 50% or more of all cat's claw exported from Peru is actually guianensis and not tomentosa.

Phytochemical analysis by various research groups shows that guianensis does have a higher percentage of TOA alkaloids and lower percentage of POA alkaloids than tomentosa. Therefore, if consumers are buying products from manufacturers that aren't controlling the cat's claw harvest and are simply buying large lots of "cat's claw" from the Peruvian or Brazilian brokers (and there are many), there's a good chance that the bulk material and resulting end product will be partly or mostly guianensis and will contain less POA alkaloids. But personally, I haven't bought into the idea that TOAs are "bad," yet.

The fact is, there are only two studies reporting that TOAs lower immune response or lower the POAs' beneficial effect on the immune system. This research was funded by or performed by the only company selling a TOA-free cat's claw product--and these studies have not been confirmed independently. In one of these studies, to get these results, major modification of the alkaloids tested was performed. The end products tested in no way represented how the alkaloids appear in the natural bark or root--and in what ratios. These were manipulated test-tube studies (in vitro) and were not confirmed in animals or humans. The only human testing in this journal article and study reported that they gave their POA extract (TOA-free) to 13 HIV-positive patients, and at the end of 5 months six out of the 13 patients actually had a decrease in leukocytes (one of the immune cells that the extract is supposed to increase)! There was only a modest increase in lymphocytes and "no significant changes of T4/T8 cell ratios were observed."

Earlier studies by the same scientists and information in their patents reported that the alkaloids' actions are further potentiated (sometimes by 100%) in the presence of catechins (a catechin is a type of tannin, present in the bark and root). But it seems that no allowances were made in this "anti-TOA" study for adding these catechins to the individual alkaloids or the combination of alkaloids they tested. If one reads the early research and the patent documents (which I did), there seems to be some contradictions in this new research. For example . . . if isorhynchophylline is a TOA (and it is) and it was documented and patented to increase phagocytosis (and it was), why would new research now try to indicate that all cat's claw TOAs are "bad" and are decreasing the phagocytosis effect? This certainly seems contradictory.

In addition, in U. tomentosa, the amount of the naturally-occurring POAs are significantly higher than the naturally-occurring TOAs (verified in many published studies by independent research). This (to me, anyway) has meaning. For a very small amount of chemicals (the TOAs) to affect a much larger percentage of chemicals (the POAs) adversely and significantly, these TOAs should (logically) have a pronounced negative effect at small dosages. Right? The new "anti-TOA" research states that the POAs' beneficial immune effect can be diminished by 30% in the presence of only 1% TOAs. So, then: why didn't anyone notice these pronounced negative effects when they were testing them to see if they actually increased phagocytosis? Their earlier research and patents indicate that they tested all of these TOAs for biological properties and published that they had no effect on phagocytosis. It certainly doesn't seem logical to me that they wouldn't have noticed a striking negative effect and, personally, it makes me question the scientific methods (and motivations) used in this research. In addition, true independent research by other scientists working with vine and root decoctions and whole oxindole alkaloid extracts continue to report an in vivo and in vitro immune stimulation effect in the presence of these "bad" TOAs (which were present in the extracts tested). Am I being too logical?

These same scientists are also purporting the presence of a "new chemotypes" of Uncaria tomentosa growing in the jungle--one that has more TOAs and one that has more POAs (or no TOAs). This was reported based on a sampling of only 16 (supposed) Uncaria tomentosa plants in Peru. Based on their published research and the alkaloid content, this "new genotype" has an alkaloid ratio remarkably resembling Uncaria guianensis. In my personal opinion, I think there has always been confusion as to the identities of tomentosa and guianensis. With care and knowedge, it's not difficult to differentiate the two species in the field. Otherwise, it's easy to make a mistake. A researcher in a laboratory and relying on a harvested sample from the middle of the jungle thousands of miles away . . . well, it can be confusing and mistakes can happen.

Personally, I haven't seen any mutating chemotypes of cat's claw vines in our Peruvian harvesting operations. I've seen some seasonal (slight) fluctuations in alkaloid content overall (our harvested lots have ranged from .91-1.6% total alkaloid content, with the overall average about 1.2%). I (and other Peruvian scientists) attribute these fluctuations to such environmental factors as rainfall amount and harvesting time. However, these fluctuations are pretty small and the POAs have always outnumbered the TOAs (about 10 to 1). The fact remains (and is indisputable): the scientists (and/or their associates or benefactors) publishing this new research, previously published four patents and numerous journal articles over the years confirming that their Peruvian Uncaria tomentosa samples do, in fact, have both naturally-occurring POAs and TOAs. Therefore, it would seem logical that this "new chemotype" would have to be one which contained no TOA's (which I've yet to see confirmed by independent research). Maybe I'm just confused now?

Another interesting fact is that much of the early research by Keplinger/Immodal was published for their proprietary extract of cat's claw that only extracted the POAs and was sold in Austria and Germany as an herbal drug. I am assuming that this is the self-same new "TOA-free" cat's claw product being sold in the U.S. today (as it is licensed and manufactured by the same Austrian drug company). I'm not sure, of course. But remember: all of their published documents reported that their Peruvian harvested cat's claw root bark contained naturally-occurring TOAs and POAs; it was their patented chemical extraction methods that only delivered the POAs (not that they somehow discovered a new plant that only contained POAs). Remember, too . . . one of these "bad" TOAs actually stimulates immune function--and that's in their published research and patents!

The other issue that raised my eyebrows on all this new TOA-free stuff is the relative dosages and price of the products. In natural cat's claw bark (the right species, harvested and processed correctly), independent lab analysis indicates a total alkaloid content of .7-1.5%. Most vine bark supplements are sold in 500 mg or 1000 mg capsules. So . . . 500 mg of bark at, say, 1.0% alkaloid content equals 5 mg total alkaloids per capsule. Let's just say for grins that the POA alkaloids make up at least 65% of the total alkaloids (instead of 90%) . . . so 5 mg alkaloids x 65% is 3.25 mg of POA alkaloids per 500 mg capsule of natural non-chemically altered or processed vine bark. Retail prices for natural cat's claw vine capsules range from $8-$15 for 100 capsules. So, 3.25 mg of alkaloids per capsule x 100 capsules in a bottle gets you 325 mgs of POA alkaloids in a bottle for an average price of, say, $14.00. This roughly yields a price of about 4 cents per mg of POA alkaloids. Got it?

One of the TOA-free cat's claw products sold today is sold as a box of 30 capsules selling for $14.50. Another label I found offered it in a 90-capsule box for $40.95. Each capsule was 20 mg (!) of "cat's claw root extract standardized to contain a minimum of 1.3% pentacyclic oxindole alkaloids [POAs] and to be free of tetracyclic oxindole alkaloids [TOAs]." Twenty milligrams! So 20 mg times an alkaloid content of 1.3% gets you 0.26 mgs of POA alkaloids per capsule--or about 4 capsules are needed to get just one milligram of POA alkaloids. Could that be right? So in a box of 30 capsules you get just 600 mg total of root bark at 1.3%--or 7.8 mg of alkaloids per box of 30 capsules. That's $1.85 per mg of alkaloids. This same manufacturer published clinical observatory trials years ago (1980s) with cancer and AIDS patients taking an average of 20 mgs daily of POA alkaloids (or the equivalent of 76 of these 20 mg caps daily!).

So let's assume that I'm buying into the new TOA/POA research (that 30% of POA effectiveness is lost in the presence of TOAs). Taking natural vine bark capsules, I'd need to take 30% more to get the same effect as theirs (since it has a very small percentage of naturally-occurring TOAs). At a price of 4 cents per mg of alkaloids for natural vine bark (versus their $1.85 per mg of alkaloid cost) . . . I could take a lot more than the additional 30% "needed," and still come out way ahead, financially. In fact--based on their prices--I could take 350 times more for the same price. No wonder my eyebrows were in my hairline!

Now, enter the next proprietary, patented cat's claw extract product in the market. Their claim is that their extract is a proprietary, hot-water-extract process (which observes the indigenous use of decoction preparation) that is "100% water soluble, and therefore is 100% bioavailable for absorption while passing through the gastrointestinal tract." They've filed three U.S. patents on their extraction process. Based on their patents, they basically take 150 grams of raw bark (with all its naturally-occurring POAs, TOAs, and other chemicals) and boil it for 24 hours down to 1000 ml of extract. They then dialyze this extract to remove the high molecular weight fraction (mostly the tannins and solids) and are left with a low-molecular-weight, light-yellow liquid extract (mostly the alkaloids, lipids, glycosides, sterols, etc.). This extract is then dried by frozen vacuum evaporation, and a powder is produced to make capsules yielding 7.933 ± .3.249 mg/ml of the hot water, dialyzed extract. Their process, as explained in the patents, would conceivably extract the majority of the alkaloids and sterols, leaving behind most of the tannins. However in their marketing of the product, they state that a "naturally occurring class of compounds known as carboxyl alkyl esters is the primary ingredient. "Carboxyl alkyl esters" (CAEs) are the phospholipid-like compounds that can interact with the cholesterol/phospholipid ration in cell membranes and strongly influence the membrane integrity of cell." To be honest, I haven't taken the time to research these CAEs more thoroughly (yet). Interestingly, they make no differentiation of TOA or POA alkaloids, or even mention the alkaloids in their marketing materials (however, they are cited in the patent documents).

This company has funded a great deal of clinical research on their product, including various human studies (something that has been lacking in the early cat's claw research, especially the TOA/POA research--which have all been in vitro studies). Their published research documents the immune stimulating, DNA repair, antitumorous, and cytoprotective effects of their cat's claw product. While it isn't truly "independent" research (as it was funded by the company selling the product), personally, I found this research much more believable. It validates, reconfirms, and restates much of the biologically-active properties of the early cat's claw research published by independent researchers (who weren't selling cat's claw). In its own way (and without even trying), it casts more shadows on the controversial POA/TOA research. Their labeled recommended dose is 175 mg (one capsule) twice daily. The therapeutic dosages reported in the studies in animals were around 40 mg/kg and 80 mg/kg, and 250-350 mg daily in humans. Their product currently retails for $24.95 for 60 capsules (175 mg capsules--not just 20!) As far as prices go, in my personal opinion, this seems to be much more reasonable if one is looking for a patented, clinically-backed concentrated extract of cat's claw in capsule form. (And no--there is no affiliation between me and this company selling this product!) I'm just stating my opinion based on what I have seen in the available research and comparing the two new, patented cat's claw products on the market.

Personally, I'll stick with the natural bark products (being an herbalist makes me a bit old-fashioned, I guess). I've seen too many times where nature has provided us with a great beneficial and biologically-active medicinal plant--and a rich indigenous history of effective use--but some have a compelling need to alter its chemical composition. The number of compounds present in such plants is staggering, and their interactions are subtle; science can only hope to understand most of them. I don't believe that science can state, at this point, that cat's claw's "active constitutents" are its alkaloids (or just one group of alkaloids), extract them, and expect them to work as efficiently as the natural form. We have no clue how the other 300-some-odd phytochemicals work synergistically and in complex chemical reactions with the alkaloids (or with any other single chemical we choose to say is "active").

As long as I know I am getting a good cat's claw vine bark (the correct species of plant, harvested sustainably, and processed without chemicals) with all the natural chemicals that nature put in it, and in the same ratios as are found in the plant, I'm satisfied. And, I'm saving some money too. But, to borrow a line: "Of course, that's just my opinion--I could be wrong."

Note 1: From United States Patent 4,940,725 Keplinger , et al., July 10, 1990. "Oxindole alkaloids having properties stimulating the immunologic system and preparation containing the same."
"Like in the granulocytic test, it can be found in this test, too, that the alkaloids participate in the effectiveness. An alkaloid-containing aqueous macerate stimulated the RES to a higher extent than an aqueous macerate having a low alkaloid content. When the alkaloid mixture was applied together with catechine, which does not stimulate itself, an activity increase was obtained which was similarily high as in the case of the aqueous macerate."

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