Division of Dietary Supplement Programs (HFS 810)
Dr. Susan Walker, Division Director

Dr. Barbara Schneeman, Director

I am writing a letter of public concern in response to your report in the January issue of the American Journal of Clinical Nutrition pertaining to adverse event reporting for dietary supplements.

This letter also addresses FDA agency issues that are broader than the narrow scope of your adverse event reporting for dietary supplements article, that is, issues that pertain to the whole experience the public has with the FDA in addition to its oversight of dietary supplements and drugs.

Your article in the American Journal of Clinical Nutrition sounds simple enough.  The FDA doesn’t know how many adverse events are caused by dietary supplements and wants to chart trends or changes over time.  But I’m concerned about the flawed rationale behind Adverse Events Reporting (AER).  There appears to be another hidden agenda behind the AER reporting, and the risk of very negative economic consequences on the dietary supplement industry.  If such a worthwhile endeavor, why was AER passed in Congress in a hidden manner at 2:30 AM in advance of the full public comment period?

You mention "A small but disturbing number of these products have a potential for harm or bear unsupported claims.”  But your report gave no examples.  I assume ephedra will be at the top of your list simply because there were deaths associated with ephedra used as a weight loss remedy.  The data on these deaths did not prove a causal relationship and may have largely pertained to deaths due to misuse or intentional overdosage.  Since anybody can overdose on cough syrup or aspirin with mortal consequences, one wonders if there was sufficient justification to remove ephedra from the marketplace?

WebMD says the FDA's ban on ephedra was announced with great fanfare in a December 2003 and that the ban was based on the FDA's conclusion that ephedra users risk heart attack, stroke, and sudden death. These risks, the FDA said, “far outweigh any benefit ephedra might have.”  But the current rationale for the use of equally-unsafe diet drugs is that “their benefits far outweigh their risks.”  This appears to be an inconsistent position.

The removal of ephedra from the marketplace was followed by Judge Tena Campbell’s (U.S. District Court in Utah) ruling that federal law prohibits the FDA from banning a dietary supplement based on weighing its risks against its benefits. The ruling specifically prevents the FDA from banning products that contain 10 milligrams or less of ephedra.

So ephedra was banned and the public was left with prescription-only drugs like sibutramine (Meridia) and no proven non-Rx weight loss remedies.  Sibutramine not only causes common side effects like dry mouth, constipation and insomnia, but also problems with elevated blood pressure and pulse rate (sounds like the same side effects as ephedra), and has been reported to be involved in 49 cardiovascular deaths by Public Citizen, who filed a petition that this drug be removed from the market.  Also whistleblower David Graham cited sibutramine as one of the five drugs that were still on the market that posed a significant hazard.  The Italian health ministry has suspended sales of sibutramine because of cardiovascular-related deaths. 

Bottom line, if the net result was to shift weight-reducers from ephedra to sibutramine, one wonders if there was a decline in serious side effects at all?

True, doctor monitoring is accomplished with a prescription drug, but this did not seem to reduce deaths.

Another topic of concern in your report was the statement that “vital premarket information (which is available for drug products) is often missing so that possible public health concerns generated by the adverse event reporting system, such as limited clinical information, product identification, and information on consumer use, cannot be adequately assessed.”  I don’t know how clinical information and data on consumer use can be produced prior to a dietary supplement being placed on the market?  There may be limited information, say for ginger as an example, but does that mean that a new ginger capsule producer would need to submit any available safety data on ginger supplements prior to marketing? 

What is puzzling is that existing rules regarding the introduction of a new dietary ingredient are in force, that safety data must be provided prior to marketing.  Yet hoodia supplements, intended for weight loss, were introduced into the marketplace in 2004, could not have escaped the attention of the FDA given that hoodia was given widespread publicity on the 60 Minutes TV program, yet according to Wikipedia, no published peer-reviewed double-blind clinical trials have been conducted on humans to investigate the safety or effectiveness of Hoodia gordonii in pill form as a nutritional supplement. 

The FDA took no action, to my knowledge, to notify hoodia makers that their product was a new dietary ingredient.  It’s as if the FDA is wishing a new supplement will be introduced and kill a lot of Americans so the agency can sweep in an invoke draconian measures to limit public access to natural remedies.  Why else would the FDA persist in allowing such a loose rope over supplements? 

Fortunately, according to Wikipedia, many hoodia supplements have none of the active ingredient and when the active ingredient is supplied, it is rapidly degraded by the liver and therefore the public may be left with ineffective hoodia supplements that do not measure up to the advertising for these products, which is more of an issue for the Federal Trade Commission than it is for FDA.

Your article in the American Journal of Clinical Nutrition also states that: “In other countries, where the definitions and regulations for product categories are different, products marketed and sold as dietary supplements in the United States may be marketed more like drugs and may be required to meet more extensive premarket requirements.”  Yes, but there was no mention of whether those restrictive measures overseas improve safety or only result in limiting public access to relatively safe supplements. 

In Northern Europe most countries there limit vitamin D supplements to 200 IU.  The latitude of Northern European countries ensures that most people living there will be vitamin D deficient in winter months, and 200 IU would never raise blood levels or eradicate widespread deficiency. 

What Europe is doing is taking dietary supplements that are safe and should be sold over-the-counter, and limiting their access or potency to ensure a measure of deficiency exists and a subsequent level of disease emanates, which is disease mongering at its best.  European nation restrictions on vitamin D ensure a high level of cardiovascular, bone, mood, diabetes, obesity, autoimmune and neoplastic disease exists for drug companies and doctors to treat.  The same is true for folic acid, vitamin C, and vitamin K.  The onerous grip the drug companies and doctors have over people who live in Europe is appalling.  Your report suggests the U.S. adopt similar measures.  This is alarming.  America is a nation of freedoms, not restrictions.

Your report in the American Journal of Clinical Nutrition goes on to say that “Under the Dietary Supplement Health and Education Act of 1994 (DSHEA), in the United States, it is the dietary supplement manufacturer who is responsible for ensuring that a dietary supplement is safe before it is marketed. The FDA is responsible for taking action against any unsafe dietary supplement product only after it reaches the market.” 

Please recall that your agency had information in hand regarding the falsification of relative safety data for Vioxx (it was initially shown to produce fewer gastric ulcers in the short-term, but the extended study showed there was no reduction in bleeding ulcers compared to other non-steroidal anti-inflammatory drugs), and that your agency allowed this drug to continue to be marketed and advertised till it resulted in the premature deaths of many thousands of Americans, and only a whistleblower (David Graham), who had to leave the country and report on the FDA’s lack of proper oversight in a European medical journal, finally exposed this whole fiasco. 

So what are U.S. citizens left to think?  The FDA will continue to allow unsafe drugs on the market, but not alleged unsafe supplements?  This appears to be the current state of affairs. 

Additionally your report says:  “There is no certainty that a reported adverse event can be attributed to a particular product or ingredient. However, CAERS does give the FDA the ability to organize, store, and review submitted adverse event reports more efficiently and effectively by using electronic storage, coding, and query software.”  Is the purpose of AER to save lives or produce meaningless data banks?  It is unlikely there will ever be any data produced from AER that will show a cause-and-effect relationship. 

Why didn’t your agency demand that a demonstration project be implemented before forcing AER on the whole country?  There is no evidence AER will save even one life.  I take issue with Congress for not exercising proper oversight over your agency and for passing onerous legislation that will result in, at best, a “Chinese fire drill.”

What will FDA do with the AER data?  Let’s say there is a 1.2% adverse event rate for ginger root supplements and this rises to 2.4%, a relative 100% increase. Would this increase be interpreted as (a) better reporting, (b) greater usage by the population, (c) a change in dosage by manufacturers, or (d) a true increase in side effects?

Recognize that the release to the public that a “100% increase in side effects associated with ginger supplements” would needlessly frighten consumers away from ginger supplements.  The FDA did just this when it issued a bulletin to doctors inquiring about side effects involving kava kava supplements. 

Based upon specious reports from European drug companies of liver problems with kava supplements (kava is sold as a drug in Europe), the FDA chose to issue a warning, which caused consumers to back away from taking kava supplements.  The $25 million kava industry was destroyed.  Kava farmers in Asian-Pacific areas plowed over their fields.  Later, scientific reviews found there was no evidence that kava produces liver toxicity.  No apologies were ever issued from your agency over this misdirection.

It appears the FDA is on some kind of witch hunt regarding dietary supplements with the objective to reign them in as controlled drugs.  It is frequently stated that DSHEA must be revoked to protect the public.  But isn’t it ironic that the lesser- regulated supplement industry produces products that are far safer than the highly-regulated drug industry.  The widely cited study showing that properly-prescribed drugs, administered by a nurse in a hospital, produce over 106,000 deaths a year, is an example.   (Jason Lazarou, et al, "Incidence of Adverse Drug Reactions in Hospitalized Patients," JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Vol. 279, No. 15 (April 15, 1998), pgs. 1200-1205).

While dietary supplements are safer than aspirin (kills about 2000 annually, bleeding gastric ulcers), acetaminophen (Tylenol kills about 150 a year due to liver toxicity), table salt (Center for Science in the Public Interest says excessive sodium in the diet kills 150,000 Americans every year), food (in the United States around 76 million cases of food-borne illness occur annually, resulting in 325,000 hospitalizations and 5,000 deaths), and chlorinated tap water (cancer from chlorinated water accounts for 6,500 cases of rectal cancer and 4,200 cases of bladder cancer in the United States each year), your agency has elected to become a closer watchdog over dietary supplements.

Your published report brought up the topic of multi-ingredient supplements, which pose a problem for safety tracking.  Multivitamins were used as an example.  Yet the Poison Control Center data for many years running does not report one fatality associated with multivitamins. 

Your paper goes on to say that “adverse event reports in and of themselves typically cannot generate conclusive evidence about safety of a product or ingredient” and that the system “can generate signals of possible public health problems.”  This is the very witch hunt I allege your agency is about to undertake. 

Just exactly what do you think the public is going to perceive when AER reporting information is affixed to dietary supplement labels?  Isn’t the public going to perceive that dietary supplements are inherently unsafe?  Isn’t there going to be a big drop in dietary supplement usage when AER reporting goes into effect and is announced in the news media?  (Recall the kava episode.)  Is this the real intention of AER?

What is stupefying is that the FDA intends to monitor post-marketing safety data provided by supplement manufacturers, claiming this is required of drug manufacturers.  But in fact it is reported that 71% of the post-market safety evaluations that drug companies promised to undertake for currently-approved drugs, have not even been initiated.  According to an audit by the inspector general of the US Department of Health and Human Services, out of 2,353 post-market commitments from fiscal years 1990 to 2004, only 6 percent had listed start dates for studies; 21 percent had projected completion dates.

I am in a unique position because I have, for the past few years, served a dietary supplement company in answering consumer questions and problems.  I can tell you the public will overwhelm supplement companies with innocuous AERs.  The public will not be able to discern serious from transient or trivial side effects.

Is diarrhea worthy of an AER?  What if it occurs from use of a dietary supplement among a 95-pound older woman, which could result in dehydration?

What about the case of a man who ended up in the emergency room after taking a dietary supplement capsule and subsequently aspirated the capsule back into his lungs?  This was certainly dietary supplement-related.

What about the common problem of loose stool with magnesium pills?  This occurs long before overdose occurs, and is common.  Won’t the tabulation of AERs like these result in undue costs to supplement companies?

Iron pills are potentially the most dangerous dietary supplement.  They can kill small children who take them and are frequently used by those who intentionally want to overdose on a pill that will induce death.  It is still puzzling why the FDA has taken no action to limit iron pills to carbonyl iron (Ferronyl) only, since this form of iron has not produced any deaths and can even be tolerated in high doses. 

I can tell you there are many doctor-provoked AERs.  One of the most frequent doctor-provoked AERs is glucosamine.  Doctors incorrectly inform their patients with high-blood sugar, who happen to be taking this supplement, that it is the cause of their blood sugar problem.  This is based upon a study that used intravenous glucosamine, which raised blood sugar.  But controlled oral glucosamine studies disprove this.  Doctors continue to drop the mistaken idea in their patients’ heads that the glucosamine raised their blood sugar.

Another common doctor-induced AER is ginkgo biloba, which doctors say over-thins the blood and should not be used with prescription blood thinners.  This is based upon numerous case reports of hemorrhage associated with ginkgo use.  But controlled studies do not show that ginkgo induces hemorrhages.

All that is needed is a concerted effort by doctors to advise their patients to report specious AERs, and the witch hunt will be under way.

Your agency appears to have a single misdirection when it comes to dietary supplements, to save the American public from safe dietary supplements.  In reviewing the dietary supplement division of the FDA, just exactly who is assigned within your agency to uphold DSHEA?  It is sad when citizens must write letters like these and challenge your agency to properly protect the public and to continue to maintain public access to dietary supplements that the current DSHEA law requires.

Bill Sardi, President

Knowledge of Health, Inc.

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