© Geriatric Times. All rights reserved.
Alternative Medical Treatments May Put Elderly Patients at Risk
by Richard A. Sherer
A 57-year-old woman reported that she had been experiencing nausea,
abdominal pain, watery diarrhea, sweating and weakness intermittently for about
two months. The attacks, she said, lasted about 24 hours but left no residual
effects. Her physical findings were unremarkable. Clinicians were puzzled by
the unaccountable symptoms. Questioning revealed that the attacks had begun
after she started taking capsules containing milk thistle (Silybum
marianum) that were supposed to promote liver cleansing and cure headaches.
Not surprisingly, the attacks ceased when she was persuaded to discontinue
using the herbal preparation.
The story itself is hardly a milestone in the annals of medicine, but it
does serve to illustrate the difficulty facing many clinicians today as the use
of herbal dietary supplements, Chinese medicinals and various types of
alternative or integrative treatments proliferates. In many cases, the effects
of such treatments are far more serious than occasional bouts of gastric
distress.
Self-prescribed herbal treatments carry their own sets of side effects, but
they can be even more serious-and sometimes deadly-when innocently combined
with prescription medications. Physicians now need to be more aware than ever
of the possibility of an over-the-counter preparation interfering with a
patient's recovery.
"Two years ago, we realized there were virtually no prospective studies
looking at how herbal dietary supplements interact with conventional
prescription medicines," Bill Gurley, Ph.D., an associate professor of
pharmaceutical sciences at the University of Arkansas Medical Sciences College
of Pharmacy, told Geriatric Times. "These preparations are becoming
ubiquitous. In 1998, JAMA (280[18]:1569-1575) reported that 15 million
people take herbal dietary supplements with conventional drugs, including at
least 3 million who are elderly."
"The elderly are the greatest concern," Gurley added, "because of the
potential to experiment with these alternative medical applications. A number
of these supplements contain a whole variety of chemical ingredients that
interact with enzymes, other drugs and a whole variety of mechanisms. We were
surprised at how few studies had been done, and we were looking at some of the
top-selling herbal dietary supplements."
Gurley and his associates were alerted to the need for comprehensive data
about the interactions between herbals and prescription medicines when a
patient with a kidney and pancreas transplant suddenly began to show symptoms
of rejection, even though she was receiving the immunosuppressive agent
cyclosporine. The patient had begun using St. John's wort (Hypericum
perforatum), a popular herbal with antidepressive properties. On
investigation, the Arkansas researchers found that St. John's wort appeared to
induce cytochrome P-450 3A4 (CYP3A4) enzyme activity and p-glycoprotein (P-gp)
expression, both of which served to inhibit absorption of the cyclosporine.
"Four weeks after stopping the St. John's wort, her cyclosporine levels went
back up above the acceptable range," Gurley said, "but the patient now appears
to have chronic rejection. She may end up losing the kidney."
A later case involving another transplant patient served to reinforce the
team's findings.
The Arkansas researchers are not the only investigators who have turned up
evidence of a conflict involving St. John's wort. In February, the U.S. Food
and Drug Administration issued a warning about the use of St. John's wort and
indinavir (Crixivan), a protease inhibitor used to treat HIV infection. This
came after a report in The Lancet (2000;355[9203]) that the herbal
"substantially decreased indinavir plasma concentrations, potentially due to
induction of the cytochrome P450 metabolic pathway."
The FDA notice also warned, "It is expected that St John's wort may
significantly decrease blood concentrations of all of the currently marketed
HIV protease inhibitors (PIs) and possibly other drugs (to varying degrees)
that are similarly metabolized, including the nonnucleoside reverse
transcriptase inhibitors (NNRTIs)."
In a presentation at the 1998 Annual Scientific Assembly of the American
Academy of Family Physicians, researchers Victoria Rand, M.D., and Ellen
Hughes, M.D., from the University of California at San Francisco, warned that
St. John's wort appears to involve the serotonergic pathway. They advised their
listeners that it should not be used with any selective serotonin reuptake
inhibitor (SSRI) such as fluoxetine (Prozac).
Other researchers around the world have reported problems with a range of
herbals. Last year, three clinicians at the U.S. Naval Medical Center in San
Diego reported two cases of hepatitis involving patients who were taking
preparations containing bee pollen or a combination of bee pollen and chapparal
in addition to prescription medications. When the herbals were discontinued,
both patients returned to normal, even though none of the prescription drugs
had been discontinued. The physicians reported in Southern Medicine
(1999;92[11]): "A review of the English-language literature revealed several
reports [4-6] of acute hepatitis after the ingestion of herbal preparations
such as chaparral (Larrea tridentata), germander (Teucrium
chamaedrys), Chinese herbs (Jin bu huan, ma-huang), skullcap
(Scutellaria galericulata), mistletoe (Vissum sp), senna
(Cassia angustifolia), and valerian root (Valeriana
officinalis)."
Gurley told GT that two other popular herbals, Ginkgo biloba and
ginseng, are known to cause interaction with prescription medications,
especially if they are taken in combination.
"Ginkgo can potentiate warfarin and ginseng attenuates warfarin," he said.
"We have a number of case reports. We're now looking at the actual mechanisms
behind the interactions to see if the effect is on the metabolism or the
absorption."
Other studies have reported adverse effects from a variety of Chinese
medicines, including one containing a supplement called Ephedra, also known as
ma-huang. At least one case of stroke has been associated with the use of
ma-huang.
Despite the risks, sales of herbals, dietary supplements and alternative
compounds reportedly are growing by 15% to 25% a year. The public appetite for
unorthodox treatments has grown to the level that, last March, President
Clinton established a special White House Commission on Complementary and
Alternative Medicine Policy. Part of the commission's charge is to maximize
"the benefits to Americans of complementary and alternative medicine"-a
statement that presumes the unquestioned value of such preparations.
"There's lots of lobbying going on," Gurley noted. "This is a $15 billion a
year industry. I don't mind people making money, but I don't want there to be
fraudulent products on the market or to have products out there that are going
to be dangerous."
For the most part, herbal compounds sold over the counter are given a
regulatory pass by Congress. This exempts them from the pre-marketing studies
and reports required of more mainstream drugs. Manufacturers of alternative
treatments avoid regulation almost entirely if their labels do not mention a
disease or promise a cure. A spokesperson for the FDA summed up the legal
policy: "We can only regulate what is on the label. A product is not allowed to
make reference to a disease on the label. Once a product makes a disease claim
on the label, we have the authority to take action."
Only if there are significant problems reported to the FDA for a particular
product is the agency allowed to require the manufacturer to provide proof of
its safety. "The FDA doesn't have nearly the degree of freedom to investigate
these things as it does with conventional medications," Gurley said. "A number
of the chemical compounds that are in these herbal dietary supplements are
known to affect biological systems. Many of them could be defined as
drugs."
In addition, because of the lax regulation, there are often problems with
quality control. One recent study reported:
Batch-to-batch variability, however, is a significant problem with
herbal preparations. Companies that produce these preparations generally do not
employ rigid quality controls, do not have adequate personnel or standards, and
do not evaluate their products for purity and reliability. Contradictory
pharmacologic effects have also been reported as a result of herbal
preparations containing different subspecies of plants or having alterations in
the chemical composition of active ingredients. Because herbal preparations are
usually not evaluated for purity and consistency of active compounds, they
often contain accidental contaminants, such as allergens, pollen, mold, and
mold spores. In addition, some herbs are edible when immature but poisonous at
maturity.
In a recent report on ma-huang, Gurley and his colleagues wrote, "Ephedrine
alkaloid content varied considerably between products. Half of the products
exhibited discrepancies in label claim and actual alkaloid content in excess of
±20%. One product was completely devoid of ephedrine alkaloids."
Clinicians, especially those treating an elderly population, are likely to
encounter numerous patients who are self-medicating with one or more dietary
supplements. In many instances, these patients may withhold the information,
fearing ridicule or censure by their physician.
"If a patient presents with what appears to be a classic drug interaction,
but none of the medications she's on would seem to be the cause, the clinician
should immediately think of herbal supplements," Gurley told GT. "Most
people who take herbal supplements don't relay that information to their
primary care physician, and most primary care physicians don't relate to that.
It's important to take a complete drug history and include herbal medications
or dietary supplements."