NEJM Editorials Rebuke Dietary Supplement Industry

01/06/2003

NEJM Editorials Rebuke Dietary Supplement Industry

BOSTON--A veritable bashing of the dietary supplement industry was delivered in the Dec. 19 issue of The New England Journal of Medicine (NEJM) (www.nejm.org). The gist of the three articles was that the dietary supplement industry is not well-regulated under the Dietary Supplement Health and Education Act (DSHEA), herbal remedies may pose health risks, and good manufacturing practices (GMPs) are not in place to guarantee quality assurance.

Most attention centered around "Botanical Medicines: The Need for New Regulations" (347, 25:2073-6, 2002), by Donald M. Marcus, M.D., of Baylor College of Medicine in Houston and Arthur P. Grollman, M.D., of the State University of New York in Stony Brook. The authors discussed DSHEA, saying the supplement industry needs new regulations. "By broadly defining herbs and other botanicals as 'dietary supplements,' DSHEA substantially altered the definitions, standards and mechanisms under which claims about the effectiveness and safety of these products are evaluated and enforced," Marcus and Grollman wrote. "This classification, which we believe to be inappropriate, has resulted in a serious and growing public health problem."

Marcus and Grollman suggest the industry suffers a lack of standardization. "Consistency in composition and biologic activity are essential requirements for the safe and effective use of therapeutic agents," they wrote. "However, botanical preparations rarely meet this standard, as a result of problems in identifying plants, genetic variability, variable growing conditions, differences in harvesting procedure and processing of extracts, and above all, the lack of information about active pharmacologic principles."

In terms of supplement safety, Marcus and Grollman noted pre-market safety testing is not required for supplements, and there is no mandatory requirement for manufacturers to record, investigate or forward adverse event reports to FDA. However, they also noted that while drug manufacturers are required to forward adverse event reports to the FDA, only an estimated 10 percent of serious adverse events associated with pharmaceuticals are actually reported to FDA. "The lack of reporting of adverse events to the FDA has generated concern at the level of the federal Office of the Inspector General," Marcus and Grollman wrote. "The Inspector General's report estimates that less than 1 percent of adverse events caused by dietary supplements, including herbs, are reported to FDA. Only a fraction of these are adequately investigated."

In their discussion of current regulations for the industry, Marcus and Grollman chastised the passage of DSHEA. "The Food and Drug Acts passed in the 20th century, which provided important protection to the public, were subverted by the passage of the DSHEA. This misguided legislation freed the dietary supplement industry from effective oversight by the FDA, transferring the burden of proof for establishing the safety of herbal medicines from the manufacturer to the FDA." Marcus and Grollman claim FDA is "hindered" in promptly removing dangerous products, as exemplified by the case of ephedra. The authors claimed the U.S. public supports the idea of new rules for the industry that would require FDA to review the safety of new supplements before they go to market and would regulate advertising claims regarding health benefits. In order to accomplish the new rules and regulations, Marcus and Grollman said six legislative proposals would be needed:

1) All companies involved in manufacturing dietary supplements would register their address and phone number with FDA. [This will actually be required as of December 2003 as part of the Bioterrorism Preparedness Act of 2002.]

2) Manufacturers should provide evidence of GMPs, and FDA should be given authority to inspect the manufacturers' records. Marcus and Grollman claim the botanical industry has "consistently blocked such a proposal." Michael McGuffin, president of the American Herbal Products Association (AHPA), stated, "That is not true. We have worked hard to try to get FDA to get dietary supplement GMPs in place. Now, the other implication of this paragraph is that in the meantime there are no GMPs that govern our class of goods, and that is not true either. FDA has stated to us in writing that until such time as there are dietary supplement GMPs, manufacturers of dietary supplements are required to conform to food GMPs."

3) Manufacturers should obtain pre-marketing approval from FDA by demonstrating product safety. In response to this comment, Mark Blumenthal, founder and executive director of the American Botanical Council, noted under current federal law, all new dietary ingredients--including herbs and other supplements that are introduced into the United States after October 1994--do require FDA approval of safety data supplied by the company before a product can be sold. "Under the current situation, pre-market approval on safety and claims for herbal products in untenable," Blumenthal said. He added, "Despite the potential benefits for a scientific review of the safety and efficacy of popular herbs, it is clearly not in the interests of the American consumer for the FDA to take seven to eight years to review and approve the OTC drug status of herbs when other Western industrialized nations have already done so."

4) Manufacturers should be required to report all adverse events to FDA. "AHPA has taken the position that reports of serious adverse effects should be required to be forwarded to FDA by manufacturers of dietary supplements and manufacturers of OTC drugs," McGuffin said. "That's already required for manufacturers of prescription drugs, but not generally for OTC drugs. The position we've taken is that it should be required for all of these classes, and I believe we went so far as to say also for foods. We also proposed that all of that information be readily accessible to consumers."

5) Labeling should identify herbs by their botanical and common names [which the authors failed to note is already required by FDA].

6) The Department of Health and Human Services should organize expert panels to review the safety of all dietary supplements, except for essential nutrients and single-vitamin and multivitamin preparations.

McGuffin added, "It is obvious that these articles were not reviewed by regulatory experts. These articles clearly show that NEJM has abdicated any sense of responsibility to conduct peer analysis on issues related to regulation. The article by the two doctors is so filled with errors, misrepresentations and distortions that any qualified reviewer who knows the regulations would have objected to it being published as is."

Herbal Medicines

"Herbal Medicines: What's in the Bottle?" (347, 25:1997-8, 2002), by Stephen Straus, M.D., of the National Center for Complementary and Alternative Medicine (NCCAM) in Bethesda, Md., opened by saying the popularity of herbal medications has caught the United States "in the midst of a public health experiment." Straus stated that the fact that millions of people worldwide are turning "back" to traditional herbal medicines to prevent illness is occurring "in spite of the greatest health and longevity in history in the United States and Europe." Straus stated the comments offered up by the other two articles were timely in light of this herbal trend, and that "Both articles identify serious problems with the overall quality, safety and efficacy of herbal products."

Straus' main point is that herbal medicines may not always contain what is labeled, and just because herbal products are "natural" does not make them safe. Straus pointedly mentioned PC-SPES, an herbal product touted for prostate cancer that was recently found to contain several pharmaceuticals, including diethylstilbestrol and warfarin. "What have been the reactions to reports that some herbal medicines are contaminated or toxic or that they interfere with the metabolism of drugs used to treat cancer or AIDS?" Straus posed. "Understandably, the enthusiasm of consumers for these `natural' cures has been tempered by increasing skepticism, and sales of herbal products in the United States have actually declined during the past two years." He went on to say that the public is now seeking additional information before purchasing herbal products and that physicians are more often asking patients about their use of herbal medicine, "and we are less judgmental toward patients who use them," Straus said. "An open dialogue results in better information so that consumers can choose products according to the existing evidence, such as it is, as to which herbal products appear to be the least harmful and most helpful."

The American Botanical Council (ABC) released a statement in light of the NEJM articles, and promoted the idea of an open dialogue. "ABC welcomes the opportunity for a national dialogue on improving the regulatory environment for herbal products," said Mark Blumenthal, founder and executive director of ABC. "For many years, ABC has proposed that a special expert committee be established to evaluate the literature on herbs sold in the United States to determine their safety and benefits. The primary reasons ABC translated and published The Complete German Commission E Monographs in 1998 were to offer the public reliable guidelines for the responsible use of many of the herbs officially recognized as medicines in Germany, and also to propose a Commission E-like model for the United States."

Straus finished his article by stating that while there are challenges facing the supplement industry, herbal medicines offer research opportunities that should not be ignored. "[W]e have not yet surveyed all of nature for its healing potential," he wrote. "However, both the quality of the data and the quality of the herbal products themselves must improve greatly if herbal medicines are to assume a respected place in the contemporary health care arena."

Herbal Remedies

"Herbal Remedies" (347, 25:2046-56, 2002), by Peter A.S.M. De Smet, Pharm.D., Ph.D., from The Netherlands, discussed regulation, quality, safety and efficacy of herbal remedies. He began by noting herbal products, which are considered dietary supplements in the United States, are not required to meet the same regulatory standards as drugs. He added herbal products may be manufactured without quality assurance as guided by GMPs (although he stated these standards are currently being developed) and may be marketed without FDA approval of safety and/or efficacy. De Smet also commented on labeling claims for herbal products, some of which suggest they can be used to treat disease.

As for quality assurance, De Smet stated it is important to make sure herbal remedies are controlled to avoid contamination with adulterants. "For commonly used herbal remedies, the U.S. Pharmacopeial Convention is developing standards for product quality and monographs that review chemical, pharmacologic and therapeutic data," De Smet wrote. "When an herbal product is labeled, `U.S. Pharmacopeia' or `National Formulary,' the DSHEA [Dietary Supplement Health and Education Act] requires that the product comply with the standards for product quality. Although this system may be useful to the extent that manufacturers are willing to abide by it, its voluntary nature leaves the door open for inferior products."

In his discussion of safety, De Smet stated, "Contrary to popular belief, the use of herbal remedies can pose serious health risks." Among the adverse effects of herbal remedies, De Smet listed neurotoxicity and renal toxicity as possibilities, and named ma huang and kava as possibly dangerous herbs.

On the plus side, De Smet noted that Ginkgo biloba, hawthorn, saw palmetto and St. John's wort all show promise in terms of efficacy. In terms of ginkgo, De Smet noted it has been shown in long-term, randomized, placebo-controlled trials to have positive effects in patients with Alzheimer's disease and multiinfarct dementia. As for hawthorn, De Smet stated it has shown efficacy in animal models for having "a positive inotropic action and prolongation of the effective refractory period, some vasodilating properties and increased coronary blood flow."

Saw palmetto didn't come off too badly under De Smet's microscope, as he noted the herb has been shown in clinical trials to have a superior effect to placebo for treating symptoms of mild to moderate benign prostatic hyperplasia. St. John's wort, however, didn't fare as well. De Smet stated the use of this herb and its major constituent, hyperforin, in clinical trials for mild to moderate depression may have had methodologic quality issues or publication bias. While De Smet did mention several trials in which St. John's wort proved effective, he latched on to the recent government-funded trial that demonstrated the herb was no more effective than placebo for treating major depression. And, of course, he highlighted the interactions St. John's wort has with prescription pharmaceuticals.

In conclusion, De Smet stated, "Clinicians should not prescribe or recommend herbal remedies without well-established efficacy as if they were medications that had been proved effective by rigorous study. However, these products continue to have great appeal to patients, and this reality cannot be ignored."

Share this article: Email, Slashdot, Digg, Del.icio.us, Yahoo!MyWeb, Windows Live Favorites, Furl
Add this article feed to: RSS, My Yahoo, Newsgator, Bloglines

Sponsored Links	Natural Products INSIDER Announcements