| U.S. Dept. of Health & Human Services |
HHS News Release, Feb 28, 2003
HHS Acts to Reduce Potential Risks of Dietary Supplements
Containing Ephedra
The Department of Health and Human Services (HHS) today announced a series of
actions designed to protect Americans from potentially serious risks of dietary
supplement products containing ephedra.
The results of a RAND Corporation study commissioned by the National
Institutes of Health, as well as other recent studies, provide additional
evidence that ephedra may be associated with important health risks. The Rand
report also finds only limited evidence of health benefits resulting from
ephedra use.
On the basis of new evidence in the medical literature and in adverse event
reports, there are reasons for heightened concern that dietary supplements
containing ephedra may present a significant and unreasonable risk of illness
and injury.
To protect Americans from the potentially serious risks of these dietary
supplements, HHS and FDA are going to:
- Seek rapid public comment on the new evidence on health risks associated
with ephedra to establish an up-to-date record as quickly as possible to
support new restrictions on ephedra-containing products.
- Seek rapid public comment on whether the currently available evidence and
medical literature present a "significant or unreasonable risk of illness or
injury" from dietary supplements containing ephedra.
- Seek rapid comment on a strong new warning label on any ephedra products
that continue to be marketed.
- Immediately execute a series of actions against ephedra products making
unsubstantiated claims about sports performance enhancement.
In addition, the nation's top public health officials issued strong
statements cautioning about the use of ephedra-containing products, especially
under conditions of strenuous exercise and in combination with other stimulants,
including caffeine.
"We want to caution all Americans - particularly athletes and those who
engage in strenuous activities - about using dietary supplements that contain
ephedra," said Secretary of Health and Human Services Tommy G. Thompson. "There
continue to be serious questions about the risks surrounding this particular
dietary supplement."
"FDA will do all we can to protect Americans from potentially dangerous
dietary supplements," said Commissioner of Food and Drugs Mark B. McClellan,
M.D., Ph.D. "We are particularly concerned about the risks of using products
containing ephedra during heavy workouts, with caffeine and other stimulants, in
a diet program that stresses the cardiovascular system, or by people under the
age of 18. We are also concerned about potential stresses to the body caused by
the long-term use of ephedra. The standard for regulating the safety of dietary
supplements is largely untested, but we are committed to finding the right
public health solution."
Ephedra is a naturally occurring substance derived from the Chinese herbal Ma
Huang. Its principal active ingredient is ephedrine, which when chemically
synthesized is regulated as a drug. While products containing natural ephedrine
alkaloids have long been used to treat certain respiratory symptoms in
traditional Chinese medicine, in recent years they have been extensively promoted and
used with the goals of aiding weight loss, enhancing sports performance, and
increasing energy.
Many of today's proposed actions involve a Federal Register notice,
which went on display today, reopening for 30 days the
comment period on a draft regulation FDA first proposed in 1997 and modified in
2000.
FDA's concerns about dietary supplements containing ephedra arise in part
from ephedra's mechanism of action in the body. Ephedra is an adrenaline-like
stimulant that can have potentially dangerous effects on the nervous system and
heart.
In addition, evidence is accumulating about potentially serious safety
problems following the use of ephedra-containing products. The RAND study has
concluded that ephedra is associated with higher risks of mild to moderate side
effects such as heart palpitations, psychiatric and upper gastrointestinal
effects, and symptoms of autonomic hyperactivity such as tremor and insomnia,
especially when it is taken with other stimulants.
Moreover, its review of some 16,000 adverse event reports revealed two
deaths, four heart attacks, nine strokes, one seizure, and five psychiatric
cases involving ephedra in which the records appeared thorough and no other
contributing factors were identified. RAND called such cases "sentinel events,"
because they may indicate a safety problem but do not prove that ephedra caused
the adverse event. The study recognized that such case studies are a weak form
of scientific evidence. Other unmeasured factors may have contributed, and such
serious adverse events are likely to happen (albeit at very low rates) among the
millions of users of ephedra anyway. The study also identified other such events
potentially associated with ephedra, in which other factors may have contributed
to the adverse events or in which records were inadequate.
Two recent studies of ephedra's safety were published too late to be included
in the RAND Corporation's review, and each raises further concerns about
ephedra. One, published this month in the Annals of Internal Medicine,
found that although ephedra-products make up less than one percent of all
dietary supplement sales, these products account for 64 percent of adverse
events associated with dietary supplements.
Another "case-control" study, published in the journal Neurology,
concluded that the rate of hemorrhagic (bleeding) strokes among ephedra users
was statistically significantly higher than among non-users, for people who take
doses above 32 milligrams a day. Many ephedra dietary supplement labels
recommend that users take up to approximately 100 mg of ephedra daily.
Additional relevant evidence on whether the current system of regulating
ephedra's safety is adequate comes from results under FDA's more extensive
regulation of synthetic ephedrine, which is identical to the main active
ingredient in ephedra. Ephedrine has long been available in some FDA-approved
over-the-counter and prescription drugs. It appears that the more controlled
availability of synthetic ephedrine products, which are available primarily for
approved uses for respiratory symptoms and carry mandatory warning labels, has
not been associated with the same kind of severe adverse events as have occurred
with dietary supplements containing ephedra. This long experience with synthetic
ephedrine (in over-the-counter drug products, not in dietary supplements)
suggests that significant restrictions on labeling, marketing, and/or access to
ephedrine might effectively address unreasonable risks associated with certain
forms of ephedra today.
"Although the overall evidence suggests that serious adverse events from
ephedra appear to be infrequent," said Dr. McClellan, "we know that such events
can be very serious and possibly fatal. We believe that the current scientific
evidence strongly suggests that at least some ephedra products present an
unreasonable risk. We also believe that FDA's system for regulating synthetic
versions of the chemicals in ephedra appears to have a much better track record
of safety. To give us the strongest possible basis for further regulatory
action, we are asking for quick comments on whether these dietary supplements
present an unreasonable risk of harm, and whether it makes sense for FDA to seek
new authority in this area."
Under the Dietary Supplement Health and Education Act of 1994, FDA does not
review dietary supplements for safety and effectiveness before they are
marketed. Rather, the law allows FDA to prohibit sale of a dietary
supplement if it "presents a significant or unreasonable risk of injury." This
legal standard of "significant or unreasonable risk" implies a risk-benefit
calculation based on the best available scientific evidence. It strongly
suggests that the agency must determine if a product's known or supposed risks
outweigh any known or suspected benefits, based on the available scientific
evidence, in light of the claims the product makes and in light of the product's
being sold directly to consumers without medical supervision.
In seeking comment on these issues, FDA is reopening a proposed rule entitled
"Dietary Supplements Containing Ephedrine Alkaloids." That proposal would have
required a warning statement for these products, as well as restrictions on
their potency and composition. FDA later withdrew parts of this proposed rule
because of concerns about the specific scientific evidence in the proposal,
expressed by the General Accounting Office.
In a broad action against potentially dangerous products, FDA today sent more
than two dozen warning letters to firms marketing dietary supplements that
contain ephedrine alkaloids. The letters, targeted particularly at products
making claims for athletic performance, explain that any claims their products
make about effects on the structure and function of the human body must be
truthful and not misleading. They outline FDA's view in light of the RAND report
that the claims being made are not adequately substantiated by scientific data,
and they direct the companies to submit any data supporting the claims within 15
days.
The letters also warn firms that they must not make claims about their
products' ability to treat or cure a disease or condition such as obesity. Under
the Federal Food, Drug and Cosmetic Act, unapproved products making these
"disease claims" are unapproved new drugs and therefore subject to other prompt
regulatory actions, including injunctions against firms and seizures of their
products.
FDA will also continue to work closely with the Federal Trade Commission to
ensure that dietary supplement products containing ephedra do not make false and
misleading claims. "If an ad says a product is 'safe,' the advertiser's must
have competent and reliable evidence to prove the claim," said Timothy J. Muris,
Chairman of the Federal Trade Commission. "Consumers depend on advertising for
factual information and deceptive ad claims can put a consumer's health at risk.
That's why the FTC is currently investigating a number of weight loss products
containing ephedra and we will continue to pursue aggressively marketers making
unsubstantiated claims about product safety or effectiveness."
In addition, FDA today proposed a warning label for all ephedra-containing
dietary supplements. The proposed label warns about the risks of serious adverse
events, including heart attack, seizure, stroke, and death; cautions that the
risk can increase with the dose, with strenuous exercise, and with other
stimulants such as caffeine; specifies certain groups (such as women who are
pregnant or breast feeding) who should never use these products; and lists other
conditions, such as diseases and the use of certain medications, that rule out
the use of ephedrine alkaloids.
"The steps being announced today demonstrate FDA's commitment to taking the
most effective actions possible under current law, given the state of the
scientific evidence," said Dr. McClellan. "It may be possible to use ephedra
safely, in small doses, for some purposes. But in the face of continued serious
adverse events following the use of ephedra, there is a problem. It is a problem
we are determined to fix."
Once the 30-day comment period has ended, FDA will analyze the comments and
publish its conclusions about the most appropriate approach to reducing the risk
of using dietary supplement products containing ephedrine alkaloids.
The National Advisory Council for the National Center for Complementary and
Alternative Medicine, part of NIH, is meeting March 17th to assess the evidence
on ephedra's safety and effectiveness in order to develop a research agenda on
ephedra. FDA will give that committee an opportunity to comment on today's
notice, should the committee find it appropriate to do so.
This advisory was prepared by the U.S. Dept. of Health and Human Services.
Previous HHS advisory on ephedra