Cancer Scientists Find Prescription Drugs In Herbal Supplement
by Wyn Snow, Managing Editor
months ago, SupplementQuality.com reported on a promising herbal
remedy for prostate cancer. PC SPES was achieving highly positive
results in clinical studies (see story: Herbs
That Fight Prostate Cancer). Now, however, cancer researchers
report finding three synthetic compounds in the mix.
Nagourney, MD, Director of Rational Therapeutics in Long Beach CA,
told cancer scientists at the 93rd annual meeting of the American
Association for Cancer Research in San Francisco that he and his
colleagues found three prescription drugs in samples of PC SPES
that they analyzed:
a hormone-like compound more familiarly known as DES
a blood thinner, also known as Coumadin®
a pain killer
success launches detective story of research
to Nagourney, he and his colleagues initially "were delighted that
an herbal product was effective against cancer and became intrigued
with finding out chemically what was inducing these changes. We
wanted to know what made this stuff so effective."
how PC SPES worked would be useful not only for prostate cancer
but might supply knowledge for fighting other kinds of cancer as
well, so Nagourney and Dr. Milos Sovak of the Biophysica Foundation
in La Jolla CA, in collaboration with associates at the Palacky
University in Olomouc, Czech Republic, decided to investigate.
SPES exhibits estrogenic effects, so Nagourney and Sovak began looking
for an estrogenic compound among the herbal ingredients, "and that's
where we ran into trouble," says Nagourney. "We weren't managing
to explain the types of results we were seeing."
formula for PC SPES combines saw palmetto with seven herbs used
in traditional Chinese medicine, including: licorice, reishi, Baikal
skullcap, rabdosia, Dyers woad, mum, and Panax ginseng. Marian Hajduch
of Palacky University took extracts of these herbs and tested them
for bioactivity by mixing them in test tubes with three different
strains of prostate cancer cells, both singly and in combinations.
None of Hajduch's extracts or mixtures slowed growth of the cancer
cells but PC SPES does.
Chen, PhD, of BotanicLab, Inc. (the manufacturer of PC SPES, located
in Brea CA), has gone on record explaining that PC SPES consists
of highly concentrated fractions derived from the plants noted above.
Thus, the failure of Hajduch's mixtures to inhibit cancer cell growth
is not evidence that PC SPES contains other active components. A
different extraction process or more highly concentrated mixture
might slow the cancer cell growth.
takes a new direction
Nagourney and Sovak wanted to know "What's different between our
mixture of these herbs and the manufacturer's mixture of herbs?"
To find out, they decided to analyze the various herbs and the PC
SPES mixture itself in order to identify exactly what was in each
researchers purchased samples of PC SPES from the manufacturer and
took them to the Biophysica Foundation where Dr. Allen Seligson
subjected them to analysis using HPLC (high performance liquid chromatography)
tracings look like a forest," Seligson told SupplementQuality.com.
"We compared the tracings of PC SPES with tracings of the individual
herbs and mixtures of herbs. Among the several hundred peaks, we
found three discrepancies between the tracings of PC SPES and the
herbs." The researchers identified these three discrepancies as
consisting of DES, warfarin, and indomethacin.
drugs or natural analogues?
2001, the New England Journal of Medicine published a letter
from Weinrobe and Montgomery that said they found warfarin (also
known as Coumadin®) in the blood of a patient who was using
PC SPES (NEJM, vol 345, pages 1213-1214). BotanicLab replied
that the product might contain a natural coumarin. Indeed, coumarin
compounds do appear in many plants including strawberries,
apricots, cherries, cinnamon, lavender, woodruff, and clover, so
this could be a plausible explanation.
Nagourney states there are chemical differences between synthetic
and natural coumarins. What they found was "consistent with synthetic
warfarin rather than plant-based." Warfarin is a prescription blood-thinner.
the researchers found 150 micrograms of DES per gram in their samples
of PC SPES. DES is also a synthetic compound. According to Nagourney,
"DES interacts with estrogenic receptors in a similar way to natural
estrogens, and was used as a treatment for prostate cancer decades
ago. We moved to other drugs because DES tends to cause blood clotting."
did not return phone calls from SupplementQuality.com. However,
their website states unequivocally: "DES was never an ingredient
formulated in the composition of PC SPES."
also states on its website: "Studies performed by Peter Nelson and
Michael Bonham compared the effects of PC SPES and DES on several
genes involved in the growth of prostate carcinoma, and found that
the compounds exhibited distinctly different activities." The website
quotes Dr. Nelson as saying, "The cellular effects of PC SPES and
DES are quite distinct, and I believe, based on our findings, that
PC SPES kills cancer cells through very different mechanisms than
those utilized by DES."
February 8, BotanicLab issued a voluntary recall of PC SPES, after
the California Department of Health announced it had found warfarin
in the product. BotanicLab said its independent lab results found
that the material "may instead be a phytocoumarin (a compound naturally
synthesized in various green plants) that may mimic warfarin in
processing cause chemical changes to herbs?
can. According to Staci Eisner, Technical Director at ExtractsPlus
in Vista CA, the process of transforming a plant into an extract
or concentrate can create new chemical compounds and cause others
to degrade. It might break a molecule in two, or alter a molecule
in other specific and generally predictable ways.
processing can change an HPLC tracing, but Eisner says, "These changes
should make sense. Generally speaking, the process of extracting
and concentrating herbal compounds from a plant usually would not
generate a chemical compound that is the same as a patented pharmaceutical
drugs are deliberately made of unique molecules that do not occur
in nature or through commonly used processing methods. To be eligible
for a patent, a substance has to be either man-made (synthetic)
or a new use of a natural substance. Also, manufacturers want to
make it difficult for competitors to reproduce their results. All
three of the drugs in question began their lives as patented pharmaceuticals,
although the patents have now run out and the drugs can be manufactured
and sold by others.
Upton, a leading herbalist and Executive Director of the American
Herbal Pharmacopoeia, is not surprised by Nagourney's report. He
states, "Herbalists have suspected adulteration of PC SPES for some
time. It was working too well and causing side effects that are
not typical of the herbs in the formula." However, Upton cautions
that "the jury is still slightly out" on whether PC SPES does actually
contain these substances and if it does, why they are there.
says PC SPES is not based on any formulation of traditional Chinese
medicine (TCM), which he practices. Instead, "it looks like a modern
mixture of herbs shown to have anticancer properties, some of which
happen to be Chinese herbs."
warfarin were added to the mix, the purpose from a Western point
of view would be to reduce the risk of blood clots from DES. From
the perspective of Chinese medicine, however, warfarin might be
added to enhance the herbs. Upton says, "In Chinese medicine, one
primary means of dissolving tumors is to use substances that dispel
blood coagulation and break up blood stasis. Tumors are viewed as
masses of tissue that are enervated with blood, so adding warfarin
to the mix could be seen as a legitimate method [from the TCM point
of view] for potentiating the blood-breaking effects of these herbs."
also says, "Conceptually, there's nothing wrong with combining drugs
and herbs, but in the US, supplement ingredients must be disclosed
on the label. If a product contains drugs, it cannot be sold as
a dietary supplement."
cloud and the silver lining
evidence from Nagourney and Sovak's research has not yet received
the intense scrutiny that follows publication of scientific work,
but soon will. Further investigation is also highly likely.
Blumenthal, Executive Director of the American Botanical Council
(ABC) in Austin TX and Editor/Publisher of HerbalGram, cautions
that testing of botanical substances is fraught with technical difficulties.
His experience in testing more than 500 ginseng products for ABC
taught him how challenging it can be to develop reliable and rigorous
test methods so that two independent laboratories get the same results
from the same samples.
if PC SPES does contain these pharmaceutical drugs, its future is
cloudy. If PC SPES contains drugs, it cannot be sold as an herbal
supplement. Because of the recall, PC SPES is currently not available
to prostate cancer patients. Ironically, however, this cloud may
have a silver lining.
PC SPES gets its results from DES plus warfarin, then any physician
can prescribe these two pharmaceutical medications, as Dr. Nagourney
has been doing for some of his prostate cancer patients for approximately
two years now. Also, warfarin is a powerful drug. Taking too much
can cause uncontrolled bleeding, a very serious and life-threatening
condition. Therefore, people who use warfarin, which is often prescribed
under the brand name of Coumadin®, need to have their dosages
and blood-clotting times closely monitored.
if PC SPES does contain these drugs, the current regulatory framework
for supplements worked. Richard Ko, at the California Department
of Health, was the first to find warfarin in PC SPES, triggering
a voluntary recall at the national level by BotanicLab.
SPES raises issues of testing and globalization of commerce that
all revolve around quality. Several fledgling programs have begun
to test and certify dietary supplement products and to inspect and
certify the manufacturing facilities that produce them. The organizations
developing these programs include:
Nutritional Foods Association
these programs have become widely adopted throughout industry and
the marketplace, it will be difficult if not impossible for a manufacturer
to sell a product containing pharmaceutical drugs under a dietary
any manufacturer who passes good-manufacturing-practice (GMP) inspections
today must have a reliable process for verifying the identity of
raw ingredients from anywhere in the globe. To pass these inspections,
manufacturers must also establish and follow procedures that ensure
ingredients do not become contaminated at any stage of the manufacturing
PC SPES contains prescription pharmaceuticals, there are only two
ways this could happen: accidental contamination or deliberate adulteration.
If PC SPES was deliberately adulterated at one or more stages in
the supply, manufacturing or distribution process, then the law
was knowingly broken which is a very different issue from
whether a new supplement is both safe and effective.
old folk injunction advises people to be careful what they wish
for. Indeed, if PC SPES was adulterated, this is a case where the
wished-for success attracted a level of scientific scrutiny that
proved its undoing.
Blumenthal; Executive Director of the American Botanical Council,
Austin TX; Editor/Publisher of HerbalGram. Personal communication,
18 April 2002.
Inc., Brea CA. Information from website, including press release:
"BotanicLab pursues investigation of 'compound' found in PC SPES."
Eisner; Technical Director at ExtractsPlus, Inc., Vista CA. Personal
communication, 19 April 2002.
A. Nagourney, MD; Medical and Laboratory Director of Rational Therapeutics
Testing Lab; also affiliated with Memorial Medical Center and UCI
Medical Center in Orange CA. Personal communication, 18 April 2002.
Seligson, PhD; chemist and General Manager, Biophysica Foundation,
La Jolla CA. Personal communication, 18 April 2002.
Upton; herbalist, Executive Director of American Herbal Pharmacopoeia,
Santa Cruz CA. Personal communication, 19 April 2002.