In March 1996 a 20-year-old Long Island, New York, college student died after ingesting eight tablets of Ultimate Xphoria, a dietary supplement whose main ingredient is the stimulant herb ephedra, also called "ma huang" and "Chinese ephedra." Practitioners of Ayurveda (traditional Indian medicine) and traditional Chinese medicine have used this herb for millennia to treat respiratory ailments. And a health food industry representative has stated that every day roughly five million Americans consume ephedra products. Should ephedra dietary supplements be reclassified and regulated?
"Ecstacy" Not Ecstasy
Promoters claim that ephedra preparations marketed under such names as "Cloud 9," "Go For It," "Herba Fuel," "herbal ecstacy ¢ ," and "Up Your Gas" improve mood, enhance sexual pleasure, and facilitate weight loss and bodybuilding. Some ephedra products are marketed as substitutes for "ecstasy" (also known as MDMA), an amphetamine derivative used illicitly as a street drug. For example, Internet advertisements describe "herbal ecstacy" as "the world's first 100% natural, organic, legal and safe alternative to a harmful, illegal recreational chemical" with "positive effects ranging from increased energy to euphoria."
Ephedrine, the primary active constituent of ephedra, is structurally similar to amphetamines and can increase blood pressure and heart rate, sometimes disastrously. According to the Centers for Disease Control and Prevention (CDC), during the period December 1993Â®Â¢September 1995 the Texas Department of Health received over 500 reports of adverse effects associated with the consumption of ephedrine-containing dietary supplements. These effects included headache, heart attack, hypertension, paranoid psychosis, seizures, stroke, tachycardia (rapid beating of the heart), and vomiting. At least 15 deaths in the U.S. have been linked to the use of herbal dietary supplements that contained ephedrine. The U.S. Food and Drug Administration (FDA) has indicated that, since consumers may not recognize the relationship between an illness and ingestion of ephedra, significant underreporting of adverse effects probably occurs.
In late 1994 Kent State University student Jennifer Pumphrey carried out a survey of 10 randomly selected health food stores in Cleveland, Ohio. Employee remarks concerning ephedra-containing products included the following.
* It's one hundred percent herbal...You won't find side effects here, only in drugstores.
* There are no side effects, because it's natural and not like a drug. Your body needs it anyways.
* It's not a drug, because it hasn't been taken out of its natural state.
Employees specified only one contraindication (something that makes a particular treatment inadvisable) and one side effect and only in two stores.
The botanical products industry has grown largely because of the widespread erroneous notion that the "naturalness" of naturally occurring substances makes them safer as drugs or medicines than artificial substances. However, natural toxins abound in the plant kingdom. And many conventional medicines were originally derived from plant materials.
Distrust of the pharmaceutical industry typically accompanies the belief that "naturalness" signifies safety. Many consumers seem unaware that the profit motive drives not only the pharmaceutical industry but the botanical-products and health-food industries as well. One of the major distinctions of the pharmaceutical industry is the high degree of regulatory constraint on its activities. Most notable is that the industry cannot market a new product unless it has proved the product both safe and effective to the satisfaction of the FDA.
The health food industry is not thus encumbered. Certainly it has not been since the arrival of the Dietary Supplement Health and Education Act (DSHEA) of 1994. DSHEA classifies herbs and concentrates, extracts, and constituents of herbs as "dietary supplements" and shelters such products from drug and food-additive regulations. The act also transferred the burden of proof of safety from supplement manufacturers to the FDA. In other words, the FDA can ban sales of a dietary supplement only if the agency has demonstrated that the product is dangerous even if the supplement contains substances identical to drugs. The FDA initially proposed to remove oral ephedrine products from the nonprescription drug market on the basis of their use in the production of street drugs and their misuse as stimulants and weight-loss facilitators. In 1995 an FDA advisory committee recommended requiring warning labels (describing, for example, side effects) for herbal dietary supplements that contain ephedra. The committee also recommended banning label claims pertaining to energy enhancement, euphoria, muscle-building, and weight loss. That April the FDA warned consumers not to use ephedrine-containing dietary supplements portrayed as substitutes for street drugs and set up a toll-free number to receive reports of adverse reactions to ephedrine products.
In August 1996 the advisory committee recommended cautionary labeling instead of withdrawal of the products from the market. Although the committee did not as a whole make recommendations concerning safe levels of ephedra consumption, those members who did make such recommendations suggested levels much lower than those of some dietary supplements.
Herbal Field Day
Marketers of herbal dietary supplements can make unsubstantiated health claims yet need not report adverse reactions to anyone. Moreover, the labels of herbal dietary supplements that contain ephedra often include misinformation on ingredients and appropriate dosage and lack information on contraindications and adverse effects. For example, lab analysis of a product whose label described "wild Chinese ginseng" as the only ingredient disclosed the presence of ephedrine (45 mg per tablet) and caffeine neither of which is a constituent of ginseng. The label on this product recommended taking five tablets, a quantity equivalent in ephedrine to more than 10 times the usual recommended dose of over-the-counter (OTC) bronchodilators (asthma medications). Often, too, labels include obscure designations for ephedra or ephedrine, including "Ephedra sinica," "herba ephedrae," "epitonin," and "ma huang extract."
State and Market Responses
In response to reports of adverse effects, 21 states passed regulations stricter than federal regulations. The state regulations include prescription requirements for ephedrine products and making ephedrine a controlled substance. Ohio banned sales of ephedra-containing products but lifted the ban in late 1996 in response to health-food industry lobbying. Nebraska has outlawed all ephedrine-containing OTC products except those approved by the FDA. And the Texas State Medical Association has resolved that all ephedrine-containing products should be categorized as drugs. On August 13, 1996, the Texas Department of Health asked the FDA to prohibit the use of ephedrine in dietary supplements and most other OTC products; the exceptions are asthma medications, decongestants, and hemorrhoidal ointments and suppositories. And Nassau County, New York, has banned the sale of all ephedrine-containing stimulants.
General Nutrition Corporation (GNC) has removed ephedrine-containing products which accounted for six percent of its sales from its 2,700 health food stores. A GNC spokesman said the company was "erring on the side of safety by removing ephedrine."
Most adverse reactions to ephedrine-containing products are due to overdosing or long-term use. Ka Kit Paul Hui, director of the UCLA Center for East-West Medicine and an expert on traditional Chinese medicine, has stated that in China, ephedra is always used as a therapeutic drug, not as a food. Although ephedrine has marginal medical utility in the treatment of asthma, for example it can have serious, potentially fatal side effects. Cautionary labeling of ephedrine-containing dietary supplements would probably prevent some tragedies, though the effect on "recreational" use of the supplements would almost certainly be minimal.
In a summary statement published in the Summer 1996 issue of HerbalGram, editor Mark Blumenthal, executive director of the American Botanical Council, and coordinator Penny King stated: "Products that are clearly masquerading as substitutes for illicit drugs, are doing so under the guise of 'dietary supplements.' [DSHEA] was never intended to give these kinds of products safe harbor from federal regulation." Blumenthal and King obliquely criticized the FDA for not swiftly removing "recreational" ephedra supplements from the market, but they did not recommend reclassifying ephedra supplements.
I do. FDA regulation of all ephedra-containing supplements as over-the-counter drugs seems the most prudent course. It would control unsubstantiated label claims, discrepancies between product contents and label ingredient descriptions, and potentially harmful label directions.
Cindy F. Kleiman, M.P.H., is ACSH's Coordinator of Toxicology Projects.
(From Priorities, Vol. 9, No. 2)