The Cat's Claw TOA / POA Controversy
By Leslie Taylor
11-15-02
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 |
| Mitraphylline |
|
| Isomitraphylline |
|
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."
*The statements contained herein have not been evaluated
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