Testimony before the House of Representatives Committee on Government Reform Hearing on Dietary Supplements. (HRG Publication #1560)
Testimony of Sidney M. Wolfe, M.D.
Director, Public Citizen Health Research Group
House of Representatives Committee on Government Reform Hearing on Dietary Supplements
March 20, 2001
A former college roommate, now an investment advisor, told me two years ago that herbal/dietary supplement companies were a hot investment item because they do not have to spend money for the research to show that the products are safe and effective. In contrast to the $100 million (some companies claim more) it takes to get a pharmaceutical through the FDA drug review process, several people in the industry have estimated to me that it takes a mere $3 to 5 million to get a supplement to the market. The legal cover for this profitable investment strategy comes from the Dietary Supplement Health and Education Act (DSHEA). I thank you for the opportunity to review the increasing evidence that this 1994 law is dangerous for people in this country.
The American Association of Poison Control Centers (AAPCC) correctly categorizes herbals/dietary supplements as pharmaceutical products since they do have pharmacologic activity. For drugs, the FDA has two opportunities to collect data on safety: legally mandated pre-market safety studies and post-marketing adverse reports. For dietary supplements, neither of these is required of the industry.
Scope of the Problem :
FDA has estimated that about 10% of adverse reactions to prescription drugs are reported to the agency, most of which come from the pharmaceutical companies who are required, by law, to report such reactions. For dietary supplements, it is likely that less than 1% of such reactions are reported to the FDA, one reason being that the manufacturers have no legal obligation to report. Based on data collected by the national network of Poison Control Centers, mostly located in hospitals throughout the country, the AAPCC publishes an annual report, in the American Journal of Emergency Medicine, which tabulates the number of adverse reactions reported by its toxic exposure surveillance system.
The figure below shows, for 1994 through 1999, the number of such reports each year for dietary supplements. The total of such reports for AAPCC is 35,400 for that period, more than ten times higher than the 3000 reported to the FDA. The number of AAPCC reports would be even higher if it included those commercial herbal supplements currently categorized as botanicals/plants. Nor does it capture the non-emergent hospitalizations due to adverse reactions that are more chronic than acute.
*only cumulative FDA data available
The following chart shows the close chemical structures of PPA, ephedrine and amphetamine:
The well-documented concerns about the cardiac (arrhythmias) toxicity and brain toxicity of ephedrine (also associated with a large number of strokes due to bleeding in the brain), the known brain toxicity of amphetamine and the use of amphetamine as an appetite suppressant confirm that there are pharmacological as well as chemical similarities between all of these compounds.
Randy Sasich, M.D., the son of my colleague Larry Sasich, Pharm D., MPH, is in his third year of internal medicine residency at Barnes-Jewish, the main teaching hospital of Washington University in St. Louis. Within just a 7-month period during his residency, he took care of two patients admitted to the coronary care unit because of ephedra (Metabolife) -induced life-threatening cardiac arrhythmias. He is aware of a third patient, also discussed below, who used Metabolife and experienced an arrhythmia but was not hospitalized:
Case 1 –April 1999. This patient, a female in her late fifties, presented at the emergency room in with a dangerously rapid rate of contractions of one of the large chambers of the heart, or ventricles (ventricular tachycardia or V-tach), after using a dietary supplement for weight control containing ephedra. She was admitted to the coronary care unit for observation. She was subsequently discharged.
Case 2 –April 1999. This patient, a female in her late thirties, suffered a heart attack (acute anterior MI) and cardiac arrest while using a dietary supplement containing ephedra for weight control. She was a smoker but had no evidence of previous atherosclerotic disease of any significance. She suffered brain damage due to a lack of oxygen.
Case 3 –October 1999. A female nurse, age unknown, experienced a rapid heart rate while using a dietary supplement containing ephedra. The rapid rate was documented by her colleagues using an electrocardiogram (ECG or EKG). She was observed until her rapid rate resolved.
Two reviews of 140 adverse reaction cases reported to the FDA involving the use of ephedra alkaloids confirmed the cardiac toxicity of ephedra. The first study found that 47% of cases involved the cardiovascular system (17 cases of hypertension, 13 with palpitations or fast heartbeat, 10 strokes). There were also 7 reports of seizures. The second study found that of the 104 reports in which causation by ephedra was very likely, there were 10 cases of sudden death, nine cardiac arrhythmias, another 23 possible arrhythmic events, three heart attacks, ten cases of chest pain and 15 severe strokes.
The FDA ban on PPA was based on a much smaller number of serious adverse reaction reports in their files than now exists, even with the extraordinary underreporting discussed above, for ephedra.
Bleeding, Blood-clotting Risks of Herbals
A recent review on the potential effects of herbal medicines on blood clotting in patients being given anticoagulants such as coumadin discussed two sets of potential problems:
Supplements which, by virtue of providing additional sources of vitamin K beyond those in food, could decrease the anti-clotting effects of coumadin, thereby increasing the risks of blood clots in those patients who are already at risk for blood clots. These include Passion Flower, Juniper and Verbena.
Supplements which can increase the anti-coagulant effects of coumadin thereby increasing the risk of bleeding in such patients. These include Japonicum, ginseng, ginkgo biloba, Papaw, Red Clover and Horse Chestnut and therefore should not be used in patients on either anticoagulant or antiplatelet therapy. 
In addition, the standard text on drug interactions, Evaluation of Drug Interactions, lists several supplements, including ginkgo, ginseng, dong quai, vitamin C, and green tea as having interactions with coumadin. 
Herbal Risks During Surgery
A recent news article in the Journal of the American Medical Association, entitled Herbs and Anesthesia, quoted the President of the American Society of Anesthesiology, Dr. John B Neeld, Jr., who said that because of changes in heart rate or blood pressure in people using herbals such as St. John's Wort, ginkgo biloba and ginseng, patients should stop taking herbal medicines at least 2 to 3 weeks before surgery. He pointed out that “It is very troubling to see our patients use products that they believe will provide a health benefit but, in fact, may jeopardize their lives during surgery if they don't tell us what they are taking.” 
Short-term and Long-Term Remedies
Right now, legislation could be introduced—combined with the right signals during the FDA appropriation process and a strong version of the GMP regulations---to rapidly lessen the damage being done by this dietary supplement industry wish list masquerading as, and having the force of, a Federal Law, DSHEA. These improvements include a mandatory adverse event reporting requirement for all dietary supplement manufacturers, mandatory warnings for risks, requirements for company and product registration, and identification of the raw ingredients and the source (by country) for each of the ingredients in each product. This latter requirement is necessary to ensure that BSE-contaminated recycled cow organs do not appear on the shelves in this country as dietary supplements. In addition, mandated funds are necessary to implement and enforce the Good Manufacturing Practices regulation that will hopefully be finalized soon. In addition, FDA should be appropriated the funds to purchase the entire dietary supplement database of the AAPCC. At present, only the ephedra alkaloid cases have been contracted for by the FDA.
When the first member of this committee or of Congress or their families, has a stroke, a fatal cardiac arrhythmia, or some other life-threatening adverse reaction to dietary supplements, perhaps there will be a belated reconsideration of the damage done by DSHEA. The law will then either be significantly modified or repealed so that pre-marketing safety and efficacy testing become the preferable alternative to post-marketing human experimentation. Until then, trust the snake oil companies. Their only concern is your health.
The following appendix contains very brief summaries from 26 articles concerning dietary supplements published in the last six years in our monthly newsletter, Worst Pills, Best Pills News.
HERBAL AND DIETARY SUPPLEMENT ARTICLES
April 1995, Vol. 1 #2
Herbal Product and Liver Side Effects
February 1996, Vol. 2 #2
Adverse Reactions from Herbal Medicines
December 1996, Vol. 2 #12
DHEA (Dehydroepiandrosterone) Safety and Effectiveness Have Not Been Proven
July 1997, Vol. 3 #7
Warning: Potentially Deadly Chomper Herbal Laxative Recalled
August 1997, Vol.3 #8
Warning: Recall of More Dangerous Dietary Supplements
February 1998, Vol. 4 #2
What Do We Know About St. John's Wort?
June 1998, Vol. 4 #6
Melatonin and Increased Seizures in Disabled Children
August 1998, Vol. 4 #8
What We Know About Garlic For Cholesterol-Lowering
October 1998, Vol. 4 #10
FDA Confirms Impurities in the Dietary Supplement 5-Hydroxy-L-tryptophan
November 1998, Vol. 4 #11
Untested "Alternative Medicine" Remedies
March 1999, Vol. 5 #3
FDA Warns About Products Containing Gamma Butyrolactone (GBL)
April 1999, Vol. 5 #4
The Poor Quality of Some Melatonin Products
August 1999, Vol. 5#8
Warning! Deaths Reported With the Unregulated Dietary Supplement 1,4 Butanediol (BD)
October 1999, Vol. 5#10
More Serious Reactions and Deaths Associated with Dietary Supplements Containing GBL, GHB, or BD
Fish Oil Protects Against Second Heart Attack but Vitamin E Does Not, Italian Study Reveals
January 2000, Vol.6#1
Ineffective and Dangerous Dietary Supplements: S-adenosyl-methionine (SAMe) For Depression and the Diet Pill Tiratricol (Triax)
In the same article we wrote that the Food and Drug Administration (FDA) was warning consumers not to purchase or use Triax Metabolic Accelerator, a dietary supplement containing tiratricol, a breakdown product of natural thyroid hormone. Triax was being sold in health food stores and over the Internet as a diet pill. Excess thyroid hormone may cause serious health consequences including heart attacks and strokes.
February 2000, Vol.6#2
Hypericum Extract (from St. John's Wort) in the Treatment of Moderate Depression
April 2000, Vol.6#4
Save Your Money: Do Not Use Vitamin E for Preventing Heart Attack and Stroke
California Health Director Warns Consumers About Prescription Drugs in Herbal Products
May 2000, Vol.6#5
New Warnings! Clinically Important Drug Interactions With St. John's Wort
The Health Research Group wrote FDA Commissioner Jane Henney on March 2, 2000 urging the agency to warn American physicians and patients about all (more than 25) drugs listed in the British warning, rather than only the AIDS drugs.
June 2000, Vol.6#6
'Gold Standard' Study Shows No Detectable Benefit Derived From Coenzyme Q10 For Congestive Heart Failure Patients
Shoddy Manufacturing and Labeling Practices Found in Dietary Supplements Containing Ephedra
Not surprisingly, the amounts listed on the labels often differed sharply from the scientifically determined contents, both over-and understating by substantial percentages ranging from 0 to 154 percent.
July 2000, Vol.6#7
More Reports of Serious Drug Interactions Between St. John's Wort and the Anti-organ Rejection Drug Cyclosporine (NEORAL, SANDIMMUNE)
Warning! Do Not Use! Chinese Herbal Supplements Containing Aristolochic Acid
February 2001, V7#2
Kidney-toxic and Cancer Causing Chinese Herbal Supplements are Recalled
Ginkgo Biloba is Found Ineffective for Dementia and Age-Associated Memory Impairment in the Elderly
 Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. New Engl J Med 2000;343:1833-8.
 Letter from Ray Woosley, M.D., Ph.D, Georgetown University School of Medicine, August 18, 1999 to the FDA.
 Argento A, et al. Oral anticoagulants and medicinal plants. An emerging interaction. Ann Ital Med Int 2000; 15(2):139-43.
 Evaluation of Drug Interactions, October, 2000. First Databank, Inc.
 R Voelker. Herbs and anesthesia. JAMA 1999;281: 1882.