Time to Ban Ephedra -- Now

Roy Guharoy, John A. Noviasky


Am J Health Syst Pharm. 2003;60(15) 


Until 1994, herbal products in the United States were regulated as food supplements or food additives.[1] However, with the passage of the Dietary and Nutritional Supplement Health and Education Act (DSHEA), oversight of these products by the Food and Drug Administration (FDA) has been greatly diminished. This act allows for the production of vitamins, minerals, amino acids, enzymes, herbs, and other botanicals without submission of safety and efficacy data to or any sort of premarketing approval from FDA.[2] In fact, manufacturers of these substances are not even required to include warnings about known or potential drug interactions as part of supplement labeling. Although the act prohibits publication of unfounded statements about curing diseases, it does allow manufacturers to make "structure or function claims."[3] For example, phrases such as "boosts immunity" and "boosts memory" can be made without any supporting evidence. When promoted as "natural," the public develops a false sense of security in these products, which are fraught with adulteration and safety issues.

Because of the lack of oversight by FDA, certain herbal products have been contaminated with heavy metals, including arsenic, mercury, and lead, or contain substitute ingredients that can cause toxicities.[4,5,6,7] Inferior manufacturing practices lead to inaccuracies in product labeling. For example, products may actually contain greater or lesser amounts of alkaloids than those listed on the label. Eleven of 20 supplements tested by Gurley et al.[8] either did not include the amount of alkaloid on the labeling or had a 20% or greater difference between the amount of alkaloid listed on the label and the actual amount contained in the product.[8] Collectively, these marketing methods have made the dietary supplement market a multibillion-dollar industry with sales increasing from $8.8 billion in 1994 to an estimated $15.7 billion in 2000.[9]

Another area of concern is U.S. consumers' use of the Internet to obtain health information, which influences their decisions about health care and medical treatments. A recent study found that the majority of Internet sites claiming cancer cures through herb use supplied no evidence to justify these claims.[10] Consequently, an abundance of supplemental products of questionable value, content, and quality is now available in our country. A case in point is the growing popularity of ephedra, also referred to as ephedra herba, desert herb, ma huang, joint fir, popotillo, sea grape, teamster's tea, and yellow horse.[11] Its use in the United States has increased exponentially, resulting in a billion-dollar industry[12,13] with an estimated 12 million individuals using these products in 1999.[14] Ephedra is promoted to enhance athletic performance, weight loss, and sexual drive, and cause euphoria.

Much of ephedra's immense popularity can be attributed to the alkaloids' amphetamine-like effect. Other physiological effects include stimulation of alpha-1, beta-1, and beta-2 adrenergic receptors, which increase heart rate, peripheral vascular resistance,[13] and blood pressure.[15] Potential drug-drug interactions include an increased pressor effect when noncardioselective -blocking agents and ephedra are used together. This is a result of unopposed -receptor stimulation.[16,17,18] Interactions with monoamine oxidase inhibitors can result in severe hypertension.[19] Patients undergoing anesthesia must discontinue any ephedra-containing products to avoid potential drug- drug interactions with halogenated general anesthetics.[20]

The ease with which ephedra can be obtained is alarming, since its use has been associated with adverse cardiovascular events, such as hypertension, ischemic and hemorrhagic strokes, myocardial infarction, and fatal arrhythmias.[21,22,23,24,25,26] In addition, {12,13] caffeine is present in many products that contain ephedra alkaloids, which enhance the negative cardiovascular and central nervous system effects of ephedra. Of 140 ephedrarelated adverse events reported to FDA between June 1, 1997, and March 31, 1999, 31% were definitely or probably related to ephedra, and 31% were possibly related to ephedra.[22] The adverse events included hypertension, palpitation, tachycardia, stroke, and seizures. Thirteen patients suffered permanent injury, and 10 patients died. Another study assessing adverse-event reports from 1995 to 1997 reported 11 sudden deaths, 16 strokes, and 10 myocardial infarctions related to ephedra use.[23] Other reports of ephedrarelated adverse events are well documented in Texas, where the department of health received approximately 500 reports of adverse events, including seven deaths due to stroke or myocardial infarction.[27] The American Association of Poison Control Centers reported 1178 ephedrarelated adverse reactions in 2001, accounting for 64% of all adverse reactions secondary to commonly used herbs in the United States.[28] However, ephedra products represented only 0.82% of the herbal products for sale in the United States. Indeed, the relative risk for adverse reactions among ephedra users are 10- to 40-fold higher than the risk among those who use other herbal products.[28]

An outcry from health care professionals finally prompted FDA to initiate a study, conducted by the RAND Corporation last year, to evaluate recent evidence on the risks and benefits of ephedra.[29] The RAND study reviewed over 16,000 adverse events that occurred after ephedra use and found unreasonable safety risks, limited evidence on short-term weight loss, and minimal evidence regarding performance enhancement. Moreover, ephedra use was associated with a high risk of mild to severe adverse effects, such as heart palpitations, psychiatric and gastrointestinal effects, and symptoms of autonomic hyperactivity, including tremor and insomnia when taken with other stimulants.[29]

In a Senate hearing on the dangers of ephedra, an American Medical Association (AMA) spokesperson urged Congress to amend DSHEA to require that dietary supplements, including those products already in the marketplace, undergo FDA review for evidence of safety and efficacy. He urged that these products be required to meet standards established by the United States Pharmacopeia (USP) for identity, strength, quality, purity, packaging, and labeling, as well as to fulfill postmarketing requirements for adverse-event reporting and drug interactions.[30] It seems logical that dietary supplements, such as ephedra, should meet USP requirements since their pharmacokinetic characteristics and adverse-effect profiles are similar to those of conventional FDA-regulated drugs.[15]

In addition to AMA, the American Society of Health-System Pharmacists and American Heart Association have urged the federal government to ban sales of ephedra.[31,32]

In response to concerns about this substance, FDA has proposed mandatory warning labels on the packaging of products containing ephedra.[29] Unfortunately, the powerful dietary supplement industry has blocked that proposal from becoming a reality. However, based on the poor risk:benefit ratio, the banning of ephedra is more appropriate than just making labeling changes. Given the serious nature of the adverse events, one may wonder why FDA has not been more aggressive in dealing with these products. It is interesting to note that Daniel Troy, the general counsel appointed by President Bush to run FDA's legal division, was previously counselor for the tobacco and pharmaceutical industries.[33] No wonder, then, that FDA is handling the ephedra issue as the tobacco industry handled the cigarette-smoking issue in the 1990s. According to a recent report, Troy favors less rigorous enforcement of regulations, has stalled efforts to investigate complaints about ephedra, and has transferred a top regulatory official (who opposed his decision) out of state.[33] In addition, under DSHEA, FDA's ability to acquire scientific evidence on the risks of dietary supplements is limited, making it virtually impossible to ascertain the accuracy and validity of labeling, content, source, and manufacturer of these products.

As health care professionals, we have an ethical responsibility to become familiar with and educate consumers about the risks associated with herbal products, especially ephedra. Meanwhile, we should contact our state and federal legislators about our concerns and ask for an immediate ban on the sale of ephedra-containing products. FDA has historically done an outstanding job protecting U.S. consumers. The dangers posed by ephedra mandate that FDA not deviate from that course.


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