Correspondence
Herbal Medicine
N Engl J Med 2003; 348:1498-1501April 10, 2003
- Article
To the Editor:
In their Sounding Board article, Marcus and Grollman (Dec. 19 issue)1 are forthright in pointing out the problems that emerged from the enactment of the Dietary Supplement and Health Education Act (DSHEA) in 1994. Although Consumers Union, in its publications Consumer Reports and Consumer Reports on Health, has sought to enable patients to obtain the best possible health care, we believe that the DSHEA was an ill-conceived and misguided attempt at empowerment of consumers. In actuality, it resulted not only in confusion and mistrust on the part of consumers but also in outright harm, including deaths. The six legislative proposals outlined by Marcus and Grollman should go far in rectifying the situation. I would add a seventh: mandatory standardization of identity, purity, and potency, which is now being done on a voluntary basis by the U.S. Pharmacopoeia. However, the consumer would be even better served by knowing that the product purchased in the marketplace is identical to that used in any clinical trial of safety or efficacy.
1 ReferencesMarvin M. Lipman, M.D.
Consumers Union of United States, Yonkers, NY 10703
lipmma@consumer.org 1
Marcus DM ,Grollman AP . Botanical medicines -- the need for new regulations. N Engl J Med 2002;347:2073-2076
Full Text | Web of Science | Medline
To the Editor:
Readers expect articles published in the Journal to be peer-reviewed, presumably by an expert with relevant experience. Although the article by Marcus and Grollman focuses entirely on the regulation of botanicals, it is apparent that no expert in the field of herbal products was consulted.
An expert regulatory reviewer would have noted that products that do not meet claims on the label or that are adulterated are illegal under current state and federal laws, whether the product is a food, drug, or supplement. Our organization was coauthor of the five-year-old proposal regarding good manufacturing practices, cited by Marcus and Grollman, and I and others served as industry advisors to the Good Manufacturing Practices Working Group of the Food and Drug Administration (FDA) in 1998–1999. In addition, the botanical industry supported language in the 2002 FDA appropriation bills for the promulgation of good manufacturing practices.
The authors call for registration of manufacturers, but Congress has accomplished this aim as of next December. The authors want manufacturers to obtain premarketing approval, but notification is required for new dietary-supplement ingredients, to which the FDA can say no. Marcus and Grollman demand that adverse events related to the use of supplements be reported to the FDA, yet our organization suggests that serious adverse events associated with supplements and over-the-counter drugs should be subject to this requirement.
Michael McGuffin
American Herbal Products Association, Silver Spring, MD 20910
mmcguffin@ahpa.org To the Editor:
Marcus and Grollman call for new legislation that would give the FDA increased authority to remove unsafe dietary supplements from the market and would regulate advertising claims about the health benefits of such products. In fact, the DSHEA already provides a regulatory framework and enforcement mechanism through shared jurisdiction by the FDA and the Federal Trade Commission (FTC). For example, the FDA has the power to stop any company from selling a dietary supplement that is toxic or unsanitary, to stop the sale of a product for which there are false or unsubstantiated claims, to take action against a manufacturer for a product that poses a significant risk of illness or injury, and to require dietary supplements to meet strict manufacturing requirements (good manufacturing practices), including those governing potency, cleanliness, and stability.1 Furthermore, the FTC has the authority to enforce laws to ensure that consumers are protected against deceptive advertising and marketing claims, to investigate complaints or questionable trade practices, to seek preliminary and permanent injunctions to stop false advertisement, and to seek civil penalties for violation of trade-regulation rules.1 Instead of waging a prolonged and potentially futile political battle for legislative reform, we should immediately allocate appropriate funding and other resources to the FDA and FTC to enforce the existing regulations stipulated in the DSHEA.
1 ReferencesBernd A. Wollschlaeger, M.D.
, Miami, FL 33162
info@miamihealth.com To the Editor:
I found De Smet's review of herbal remedies (Dec. 19 issue)1 both interesting and practical. I would like to point out an oversight in Table 5 with respect to feverfew leaf, noted in the table as having positive effects in a majority of randomized, controlled trials. There have been five such trials of feverfew leaf in the treatment of migraine. Three had negative results,2-4 and one had positive results5; the fifth trial, which also had positive results, used an unorthodox design and an uncertain patient population.6 Even if the poor-quality study is included, the majority still had negative findings.
6 ReferencesPeter J. Goadsby, M.D., Ph.D.
Institute of Neurology, London WC1N 3BG, United Kingdom
peterg@ion.ucl. ac. uk 1
De Smet PAGM . Herbal remedies. N Engl J Med 2002;347:2046-2056
Full Text | Web of Science | Medline2
De Weerdt CJ ,Bootsma HPR ,Hendriks H . Herbal medicines in migraine prevention: randomized double-blind placebo-controlled crossover trial of a feverfew preparation. Phytomedicine 1996;3:225-230
CrossRef3
Pfaffenrath V ,Diener H-C ,Fischer M ,Friede M ,Henneicke-von Zepelin HH . The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis -- a double-blind, multicentre, randomized placebo-controlled dose-response study. Cephalalgia 2002;22:523-532
CrossRef | Web of Science | Medline4
Murphy JJ ,Heptinstall S ,Mitchell JRA . Randomised double-blind placebo-controlled trial of feverfew in migraine prevention. Lancet 1988;2:189-192
CrossRef | Web of Science | Medline5
Palevitch D ,Earon G ,Carasso R . Feverfew (Tanacetum parthenium) as a prophylactic treatment for migraine: a double-blind placebo-controlled study. Phytother Res 1997;11:508-511
CrossRef | Web of Science6
Johnson ES ,Kadam NP ,Hylands DM ,Hylands PJ . Efficacy of feverfew as a prophylactic treatment of migraine. Br Med J (Clin Res Ed) 1985;291:569-573
CrossRef | Web of Science | Medline
Author/Editor Response
We thank Dr. Lipman for his supportive comments and note that Consumers Union was among the first organizations to alert consumers to the dangers of ephedra in dietary supplements. Voluntary certification of dietary supplements by the U.S. Pharmacopoeia provides a false sense of security by confirming that the product contains the quantity of a particular ingredient stated on the label but providing no information about the activity or stability of the active component (or components). Certification by the U.S. Pharmacopoeia is not designed to detect adulteration with prescription drugs.
The claim by both McGuffin and Wollschlaeger that the FDA and FTC have the authority to regulate herbal products effectively is disingenuous and self-serving. In support of his position, Wollschlaeger cites an article written by the senior vice president of a trade organization that represents manufacturers and distributors of dietary supplements. These arguments have been formally refuted,1 and the “political battle for legislative reform” must not be delayed. Our recommendations for reforming the DSHEA are only a beginning; botanical medicines ultimately should be regulated as over-the-counter drugs; their current designation as dietary supplements has serious consequences for public health.2
Manufacturers of over-the-counter drugs are required by law to provide evidence of potency, purity, and safety for their products. For botanicals, the DSHEA shifted the burden of proving safety from manufacturers to the FDA, which lacks the enormous resources required to analyze the multitude of marketed herbal remedies. Similarly, the FTC lacks the authority and resources to counter misleading health claims in product advertising effectively.
The inability of the FDA to regulate products containing ephedra, despite overwhelming evidence that this herbal medicine causes thousands of serious adverse events annually, proves our point.3 The Department of Defense recently prohibited the sale of ephedra products on military bases.4 However, the FDA cannot protect civilians.
A majority of the public believes that supplements are strictly regulated by the FDA5; 68 percent believe that manufacturers are required to place warnings on labels, 59 percent believe that supplements must be approved by the FDA, and 55 percent believe that health claims for supplements must be based on solid scientific evidence.5 They are mistaken. The two spokesmen for the herbal and nutraceutical industries are technically correct in stating that dietary supplements are regulated. They neglect to mention that the current regulations are limited and ineffectual.
5 ReferencesDonald M. Marcus, M.D.
Baylor College of Medicine, Houston, TX 77030
dmarcus@bcm.tmc. edu Arthur P. Grollman, M.D.
State University of New York, Stony Brook, NY 117941
Silverglade BA . Regulating dietary supplement safety under the Dietary Supplement Health and Education Act: brave new world or pyrrhic victory? Food Drug Law J 1996;51:319-321
Web of Science | Medline2
Palmer ME ,Haller C ,McKinney PE , et al. Adverse events associated with dietary supplements: an observational study. Lancet 2003;361:101-106
CrossRef | Web of Science | Medline3
Bent S, Tiedt TM, Odden MC, et al. The relative safety of ephedra compared with other herbal products. Ann Intern Med (in press).
4
Ephedra nixed by Army, but not by FDA. New York: CBS Broadcasting, December 5, 2002. (Accessed March 21, 2003, at http://www.cbsnews.com/stories/2002/12/05/eveningnews/main531881.shtml.)
5
Widespread ignorance of regulation and labeling of vitamins, minerals and food supplements, according to a national Harris Interactive survey. Rochester, N.Y.: December 23, 2002. (Accessed March 21, 2003, at http://www.harrisinteractive.com/news/allnewsbydate.asp?NewsID=560.)
Author/Editor Response
The entry on feverfew in Table 5 of my article was based on a systematic review by Ernst et al.1 of the efficacy of feverfew in the prevention of migraine that covered the same randomized, controlled trials that Goadsby cites in his letter. There are two reasons for the different ratios of positive to negative results.
First, Ernst et al. rated one of Goadsby's studies with negative results (Goadsby's reference 4) as a trial with positive results, as Goadsby himself and a colleague have done elsewhere.2 As a result, Ernst et al. included in their review three published trials with positive effects and one with negative effects. I agree with Goadsby that one of the studies with positive findings (his reference 6) had an unusual design, since it measured withdrawal symptoms in regular feverfew users randomly assigned to receive either feverfew or placebo.
Second, another caveat was that Goadsby's reference 3 was available only in abstract form when Ernst et al. prepared their systematic review of feverfew1; it still had not been published as a peer-reviewed article when I finalized my Table 5. Whereas the initial abstract suggested a positive outcome,1 the final report indicates that the overall intention-to-treat analysis showed neither a significant prophylactic effect of feverfew, as compared with placebo, nor a dose–response relation.3 A subgroup analysis showed a positive effect in a predefined subgroup of patients with at least four attacks within the four-week base-line period, but the researchers conceded that this subgroup was too small to permit a conclusion.3
Thus, there was no preventable oversight in my Table 5, but a new trial report3 has added to the already existing uncertainty about the efficacy of feverfew as a prophylactic agent in patients with migraine.
3 ReferencesPeter A.G.M. De Smet, Pharm.D., Ph.D.
University Medical Center St. Radboud, 6525 GA Nijmegen, the Netherlands
pdesmet@winap.nl 1
Ernst E ,Pittler MH . The efficacy and safety of feverfew (Tanacetum parthenium L.): an update of a systematic review. Public Health Nutr 2000;3:509-514
CrossRef | Medline2
Silberstein SD ,Goadsby PJ . Migraine: preventive treatment. Cephalalgia 2002;22:491-512
CrossRef | Web of Science | Medline3
Pfaffenrath V ,Diener HC ,Fischer M ,Friede M ,Henneicke-von Zepelin HH . The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis -- a double-blind, multicentre, randomized placebo-controlled dose-response study. Cephalalgia 2002;22:523-532
CrossRef | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
C. Guruvayoorappan, G. Kuttan. (2007) Effect of Biophytum sensitivum on Cell-Mediated Immune Response in Mice. Immunopharmacology and Immunotoxicology 29:3-4, 337-350
CrossRef
