Ephedra Products Thin Out

Nutrition aisles that used to bulge with products containing the controversial dietary supplement ephedra are filling with alternatives like green-tea extract and bitter orange, as supplement makers try to cushion themselves from liability fears and the possibility of a government ban.

Whether the government action against ephedra-containing products materializes this spring, as many supplement makers fear, recent industry moves suggest some manufacturers have concluded that public tolerance for bad news about the herbal product has reached its limit.

"With all the bad publicity ephedra's gotten lately, and all the problems these companies are having maintaining their product liability insurance now, I can't blame [manufacturers] for coming up with something new to sell," said John Hathcock, vice president of nutrition and regulatory science for the Council for Responsible Nutrition (CRN), a trade association for the supplement industry.

An indepenent safety review of the plant derivative by the Rand Corp. is slated for March release. If the report, ordered by the Bush administration, finds ephedra hazardous, the Department of Health and Human Services could initiate action to have it taken off the market. If that happens, said Larry Sasich, a pharmacist and spokesman for the Public Citizen Health and Research Group, ephedra would be the first supplement to run afoul of the Dietary Supplements Health and Education Act of 1994 (DSHEA). "I have a feeling [ephedra] will eventually come off the market -- but it could be quite a mess first," said Sasich.

In November, General Nutrition Centers (GNC), the country's largest retailer of dietary supplements, began requiring customers to show proof they are 18 or older before buying products containing ephedra. While there has been little research to suggest ephedra exposes children to greater risk than adults, industry sources fear teens are more likely to ignore dosage directions.

Also in November, Twinlab Corp. announced it would discontinue the manufacture of all ephedra products, effective in March.

Saying that the federal government "will move as aggressively as the law and the science allow" to protect consumers from the potential dangers of ephedra, Health and Human Services Secretary Tommy G. Thompson directed the Food and Drug Administration (FDA) in October to recommend the strongest mandatory warning label for ephedra-based products. The same month, the FDA announced a new program to analyze all herbal ephedra products to make sure that they, as required by law, contain natural ingredients and not synthetic ingredients.

Meanwhile, observers say the entire $4.2 billion herbal supplement industry has been tainted by the claims and counterclaims about ephedra, the subject of probably the most serious health complaints of any supplement on the market.

"You can't have a discussion about herb safety right now without the conversation turning to ephedra," said Mark Blumenthal, executive director of the American Botanical Council, a nonprofit educational and research organization whose members include several ephedra makers. "It haunts the herbal industry, has become its Achilles' heel."

The past year or tw o have not been ephedra's best season.

Last summer, the government ordered the Rand Corp. review of the product, which, according to the FDA, has been linked to 80 deaths and 1,500 reports of health problems including hallucinations, seizures, hypertension and stroke. Under DSHEA, the FDA is required to prove a dietary supplement harmful before it can take action to limit or ban its sale. So far, said an FDA spokesperson, the agency has not publicly labeled ephedra dangerous, despite mounting reports of adverse reactions. Three years ago, when the agency proposed to set new dosage limits, industry pressure killed the move. Now, industry watchers say the Rand report may provide the proof the FDA needs to take action against ephedra.

But there's no letup meanwhile in the heat for ephedra product makers. The Justice Department announced last summer that it was conducting a criminal investigation to determine whether Metabolife International Inc., a major manufacturer of ephedra, lied to the government and withheld records. In 1998 the company's president told the FDA that his company had never received any consumer health complaints associated with Metabolife's ephedra product, Metabolife 356, which contains a mixture of ephedra and caffeine. Later, the company handed over about 1,300 such notices, including reports on hundreds of people who required hospitalization and 80 incidents claiming serious injury or death.

The National Football League banned ephedra use by its players in September 2001, citing health risks such as seizures, strokes and death. Ephedra has also been banned by the International Olympic Committee and the National Collegiate Athletic Association (NCAA). Health officials in Canada asked ephedra makers to voluntarily recall all ephedra products in January 2001. And after more than 30 military personnel died following their use of ephedra, the U.S. Army and Air Force last summer banned ephedra product sales in its stores worldwide. The Marines issued a similar ban in February 2001.

The American Medical Association also wants the product banned.

Since Jan. 1, California has required that all ephedra-bearing products have a warning label listing contraindications such as pregnancy and high blood pressure, as well as a toll-free number to call the FDA about adverse reactions. This law also prohibits sale of ephedra to minors. Several other states also require ephedra products to carry warning labels.

Ephedrine, the main active ingredient in ephedra, is a chemical relative of amphetamines that is derived from a Chinese medicinal root known as ma huang. Marketers have promoted ephedra supplements for improving athletic performance, increasing alertness and controlling weight by claiming the herb suppresses appetite and increases metabolism.

Trade groups say it's nearly impossible to know how many ephedra products are for sale in groceries, drugstores, heath food stores, convenience stores and on the Web because most aren't labeled as such. Instead, the groups say, they're labeled simply as weight-loss pills, bodybuilding supplements or energy boosters. Many contain a host of other ingredients in addition to ephedra.

Doctors say ephedra poses particular dangers for people who have high blood pressure, heart problems, diabetes or a history of seizure or stoke.

One theory is that the herb, especially when combined with caffeine or exercise, overstimulates the heart. A 2000 analysis in the New England Journal of Medicine linked at least 54 deaths and about 1,000 reports of complications to the popular supplement since the mid-1990s.

In response, ephedra industry spokesmen cite at least 55 studies that they say prove ephedra's safety when it is taken as directed. The Ephedra Education Council, an organization funded by ephedra makers to defend the herb, says there are so far no clinical studies that show that ephedra causes any adverse health events.

The CRN defends manufacturers' rights to keep products on the market until they're proven unsafe. Nonetheless, CRN categorizes ephedra as a "red-light" product in its three-light (red, yellow, green) classification system for performance-enhancing products. The designation, it says, means buyers should be 18 or over, know the supplement's adverse effects and take it only according to the label's directions.

CRN advises, but does not require, that ephedra products bear warnings about contraindications that include hypertension and kidney, liver and neurological diseases, as well as potentially dangerous interaction with psychoactive drugs and other ephedrine alkaloid-based supplements.

Meanwhile, companies that continue to sell ephedra products as well as those that have pulled theirs have begun to bring new weight-loss products to market as they await word from the federal government on ephedra's future.

Herbalife, which faces two wrongful death suits tied to its ephedra products, and Twinlab, which faces a lawsuit over a customer death following use of its Metabolift ephedra product, announced last year that they were discontinuing their ephedra lines. At the same time, they introduced new weight-loss supplements containing citrus aurantium, also known as bitter orange, which comes from orange peels. Neither company returned calls seeking comment.

Bitter orange contains synephrine, an agent that like ephedra, has been shown to speed metabolism. Safety and efficacy information on bitter orange is sparse, says the CRN's Hathcock. However, the substance is on GNC's list of products that cannot be sold to minors. New Jersey-based Cytodyne Technologies has turned to both bitter orange and green-tea extract while keeping its ephedra product, Xenadrine-RFA-1, on the market. Last year, the company introduced Xenadrine-EFX, a weight-loss pill containing a mix of green-tea extract, bitter orange and caffeine. Company president Robert Chinery said sales of the new product have already outpaced the older, ephedra-based product.

Cytodyne cites two small company-sponsored pilot studies as evidence of the safety of green-tea extract, which contains 150 milligrams of caffeine per tablet, 10 times more than the amount of caffeine in a cup of green tea. Chinery says that more studies are ongoing. Cytodyne claims that someone taking its green-tea extract product would lose about 25 pounds over a year without adding diet or exercise.

But independentexperts aren't so sure.

"Green-tea extract has market buzz because of its antioxidant properties, but basically, it's just caffeine," said ABC's Blumenthal.

Hathcock concurs. "All stimulants to one degree or another keep people moving and keep them jittery, which in fact may cause a considerable amount of weight loss. There's not sufficient evidence that green-tea extract itself actually causes weight loss, though."

Public statements by Cytodyne cast further doubt on its claims. The company recently put out press releases claiming that studies on its green-tea extract product had been published in the Journal of the American College of Nutrition and by the National Institutes of Health (NIH). That's not the case. Cytodyne's study abstracts were merely printed in programs for upcoming conferences sponsored by the NIH and the journal.

Meanwhile, ephedra-makers are being plagued by product liability insurance problems, said Hathcock. Ephedra insurance premiums have increased along with the adverse incident reports and lawsuits. Herbalife said in a 2002 federal filing that from 2000 to 2001 its product-liability insurance premium jumped from $400,000 to $2.5 million, while its coverage limit fell by $10 million to $40 million. Many companies are looking into banding together to purchase insurance, said Hathcock.

Oddly enough, some in the industry say the fracas over ephedra may have worked some positive effects.

Howard Schwartz, director of clinical research for Miami Research Associates, which conducts clinical trials for the pharmaceutical and nutritional supplement industry, says he is seeing more herb companies order safety and efficacy studies on their products, exceeding FDA requirements.

The shame, says Hathcock, is that, with more than 60 percent of Americans now considered overweight or obese, people turn to diet pills when research continues to show that eating right and exercising regularly is still the best Rx for weight loss.

"There is simply no substitute for those two," he said.