Excerpted from Detroit Free Press, Tuesday, 3 March 1998.

The Enigma Of Ephedra: Radio DJs Praise A Weight-Loss Herb The FDA Says Could Hurt You

Annie Lehmann, Free Press Special Writer -- Detroit radio has been abuzz with hype for Metabolife 356, "the all-natural weight loss supplement that will energize your life."

The sales pitch for this herbal formula, which claims to work "by raising your metabolic rate and curbing your appetite," can be heard throughout the day on WKQI-FM (95.5), WPLT-FM (96.3) and WYCD-FM (99.5).

WKQI DJ Kevin O'Neill, for one, frequently praises his diet success using the ginger-colored caplets, which are marketed by the San Diego-based Metabolife International Inc., and manufactured in Colorado Springs, Colo. The caplets can be purchased by phone.

But what listeners don't hear is that one of Metabolife's main ingredients, ma huang concentrate, also known as the herb ephedra, is at the center of a heated controversy.

Ephedrine alkaloids, which are extracted from ephedra (as caffeine is derived from coffee), "may decrease appetite and elevate mood," according to "Prescription for Nutritional Healing" (Avery Publishing, $19.95) by Dr. James F. Balch and Phyllis A. Balch, a certified nutritional consultant. But this heart and nervous system stimulant may pose a hazard, especially for people with conditions such as glaucoma, heart disease or high blood pressure or those taking antidepressant medications such as a monoamine oxidase (MAO) inhibitor.

At the 1996 meeting of the American Academy of Neurology, a medical association of more than 13,500 neurologists and neuroscience professionals, Dr. Gary M. Franklin, Professor of Neurological at the University of Washington, Seattle, presented preliminary results of an analysis that suggested use of ephedrine alkaloids was associated with acute neurologic events.

Franklin became interested in ephedrine after seeing an otherwise healthy 24-year-old woman who, almost comatose, was brought to the emergency room. "She was found unconscious at work and had multiple prior episodes of dizziness after ingesting increasing doses of ma huang for weight loss," Franklin says.

After this and similar incidents with other patients, Franklin reviewed the current federal Food and Drug Administration data on adverse events associated with ephedrine and found that there are four different levels of adverse effects resulting from its use:

• Stroke, seizure, loss of consciousness and bleeding in the brain;
• Psychosis;
• Chest pain, tingling in the arms, increased blood pressure, numbness, slurred speech and weakness in the legs, with or without migraine;
• Anxiety, hyperactivity, insomnia and nervousness.

"From a medical standpoint, I see ephedra use as potentially dangerous," Franklin says.

Dr. Peter Lewitt, neurology professor at Wayne State University, concurs: "Stimulants like ephedrine need to be used in a monitored manner. Experience has shown them to be a poor choice for appetite control because their benefits are usually limited to one or two weeks."

Herbalist Michael Ellis, president of Metabolife, says, "Ephedra is safe as long as the consumer follows label directions carefully and reads all cautions."

But the labeling is itself part of the controversy.

Metabolife, for example, advertises a 90-caplet bottle as lasting 30-45 days, implying that a two- or three-caplet dosage per day (24 mg to 36 mg of ephedrine) is the normal dosage. When the product arrives, however, the "suggested use" portion of the Metabolife label reads: "ONE to TWO caplets two to three times per day, or every four hours. DO NOT EXCEED EIGHT CAPLETS PER DAY." At 12 mg of ephedrine per caplet, a person following these instructions could be taking anywhere from 24 mg to 96 mg of ephedrine daily.

According to Ellis, some 20 million "servings" (the word the industry uses) of ma huang are taken monthly, so it is not surprising that since 1994, the FDA has investigated more than 900 adverse incidents associated with ephedra use. Most incidents, including 34 deaths, involved young to middle-aged people using ephedra for weight loss or to increase energy, says Arthur Whitmore, spokesman for the FDA.

"Those reports," says Ellis, "were anecdotal, and of the 900, only five were true injuries that could have been avoided had the users properly heeded the cautions on the label." None of the adverse event reports, he says, resulted from the use of Metabolife. Whitmore says it's impossible to know for sure unless the person reporting the adverse effects specifically cited Metabolife as the source of ephedra in the bloodstream.

Last June, however, the FDA announced a proposal to cut dosage and restrict long-term use of ephedra products. The FDA proposal would:

Prohibit marketing dietary supplements with 8 mg or more of ephedrine alkaloids per serving.

Ban labeling that suggests taking more than 8 mg per six-hour period or a total daily intake that exceeds 24 mg. This dosage was determined after medical records of reported adverse effects were analyzed by the FDA. Many of the complications occurred when the dose exceeded 24 mg per day.

Instruct consumers not to take ephedra products for more than seven consecutive days, to discourage long-term use for weight loss.

Discourage short-term excessive use for purposes of energy enhancement by labeling products to read: "Taking more than the recommended serving may result in heart attack, stroke, seizure or death."

Prohibit the use of other stimulant substances such as caffeine in combination with ephedra, because of the "increased risk of 'heart attack, stroke, seizure or death.' "

The FDA is reviewing public comment on the proposal that was solicited last summer and hopes to issue a final ruling by this summer.

Advocates for the $11.5-billion diet supplement industry, including Metabolife Inc., are critical of the FDA's proposal. Ellis says the FDA has not done any scientific studies about the effects of ephedra and that the reporting mechanisms for the 900 reported events were not valid.

"No one wants regulators more than I do," he says. Ellis wants guidelines based on "scientific studies and clinical trials," the kind he says were conducted on Metabolife by two independent laboratories.

Copies of these scientific studies and data from the clinical trials were requested for this report. Instead, letters and reports refuting the FDA proposal were received, most notably from the Scientific Advisory Committee, "a panel of esteemed academicians assembled to review the FDA Proposed Rulemaking." The Scientific Advisory Committee is supported by funds received by the Academy of Clinical, Environmental Safety and Science Coalition, a consortium of nine herbal product companies, which Ellis heads.

The FDA's Whitmore counters that "the data on the whole indicate a problem with ephedra. We have hundreds of reports that are substantiated and that indicate specific problems in otherwise healthy consumers."

Proponents of ephedra-containing supplements also point to bronchodilators (Primatene Mist) and cold remedies (Sudafed) as examples of products that, when taken as directed, often equal or exceed the FDA's proposed daily dosage of ephedrine alkaloids. These products, however, would not be affected by this proposal. The reason for the exception, according to Whitmore, is that "over-the-counter substances are in a different category than diet supplements." Also, there are enforceable standards on how the nonprescription drugs should be used and manufacturing plants are open to inspection, enabling the FDA to assure consistency, purity and reliable potency of a product.

Whitmore also points out that synthetically derived chemicals -- like those in Primatene and Sudafed -- can be measured precisely, unlike herbs, which vary in potency depending on soil and growing conditions.

Unfortunately, he said, many individuals seeking a quick fix often believe that if some is good, more is better, especially if something is labeled "all-natural."

"Consumers should be aware that just because a product is labeled 'natural' or from an herbal source it is not guaranteed to be safe," says Michael Friedman, the FDA's deputy commissioner of food and drugs in a written statement issued last June. "We urge people to talk to their doctor before using dietary supplements containing ephedrine alkaloids and to always use them with caution."

Ellis agrees with Friedman, saying "all-natural" does not mean "all safe." But Ellis doesn't believe that a product should be altered or be taken off the shelf simply because some don't use it responsibly. "There are posted speed limits, yet many people drive too fast. Does that mean you remove all cars from the road?" he asks.

If indeed ephedrine alkaloid-containing compounds can pose health risks, how did they make it to market shelves?

As a result of the Dietary Supplement Health and Education Act (DSHEA), passed in 1994, diet supplements are treated differently than pharmaceuticals even though they often contain the same ingredients as prescription drugs.

While pharmaceuticals need to be proven safe and effective in controlled studies in order to be marketed, a diet supplement must demonstrate an "imminent risk" to be removed from the shelves by the FDA. Because proving "imminent risk" is so difficult, people such as Rep. John Dingell, D-Mich., would like to undo the law. "I'd like to repeal the whole sorry mess," he said last June. The law is currently under review in the House Commerce Committee.

While herbal diet supplement manufacturers cannot by law claim that a preparation will prevent illness, they can say that it helps certain parts of the body. For instance, claiming that a compound will prevent a heart attack is prohibited, but labeling the formula as being good for the heart is permissible.

Personal testimony

Despite the controversy, people like Valerie Miller, an administrative assistant in programming and marketing at WKQI, continue to turn to diet supplements for weight loss.

She has lost 53 pounds in eight months using Metabolife and gone from a size 18 to a size 10. Because it is a product the station advertises, sample boxes were free to employees interested in trying the supplement. She takes six caplets daily, about 180 per month. Had she spent $49.95 per 90-caplet bottle, losing the 53 pounds would have cost her $800, or about $15.09 per pound.

Miller, 43, says she has tried many weight loss regimens, including Weight Watchers and grapefruit and cabbage diets, "which all work." What's different about Metabolife, she says, is that it helps curb her appetite.

Miller is aware that the six caplets of Metabolife -- totaling 72 mg of ephedrine -- she has been consuming daily for the past eight months exceeds both FDA guidelines for dosage and time limits. She contends: "I eat too much salt, sugar, beef and artificial sweetener, as well.

"It's not magic. It's a crutch," she said, "But I have definitely changed my eating habits and lost the weight slowly." Having more energy has been a side benefit, says Miller, who walks two miles three times a week and still has energy after work to clean the house that she shares with her two children. She does not take Metabolife after 5 p.m. because it keeps her awake if she does.

Miller is clear, however, that her weight loss cannot be solely attributed to taking Metabolife. "The bottom line," she says, "is that you have to change what, how and when you eat or it will all come back."

Excerpted from Detroit Free Press, Tuesday, 3 March 1998.