How Safe are Ephedrine-Free Diet Pills?

On March 1, the U.S. Food & Drug Administration will put a nationwide ban into effect on the sale of over-the-counter ephedrine diet pills.

In spite of 16,000 complaints and reports of 155 deaths that the FDA received over the past ten years, it was the untimely death early last year of 23-year-old Baltimore Orioles baseball pitcher Steve Bechler (his widow has filed a $600-million lawsuit against the makers of Xenadrine RFA-1) that brought matters to a head.

Knowing that the axe would soon fall following Bechler's death, weight loss supplement makers have been busy coming up with "ephedra-free" diet pills, which promise weight loss without the adverse effects of ephedrine.

The question is: Are these substitutes any safer? The answer is no one knows. Just like there was no extensive pre-market testing done on supplements containing ephedrine derived from ephedra or ma huang, there is also not much research on the safety record of ephedra-free weight loss formulations.

This is because of a1994 loophole law that allows herbal and food supplements to be sold under the radar of the FDA. According to this law, nutritional supplements are defined as food and do not need to undergo the stringent process that drugs go through, which can take years of research and testing. Thus, dietary supplements can be sold based on anecdotes and testimonials instead of hard scientific evidence. The burden of proof is on the FDA to prove that a supplement is dangerous to the health of consumers. For that, people have to get hurt or die first.

This worries people like Dr. Ray Woolsey, vice-president for health sciences at the University of Arizona, who told John Carey of Business World Online, "It is very likely that the substitutes for ephedra are going to be just as toxic." Another medical professional, pharmaceutical sciences professor Bill Gurley of the University of Arkansas, told Carey that there are already reports of adverse reactions to the new ephedra-free products. The ephedra substitute that health experts are concerned with the most is synephrine.

As a drug, synephrine is used in nasal sprays to unclog stuffy noses. It is effective at doing this because it constricts blood vessels. But because of that characteristic, the FDA requires a warning label that states in part, "Do not use this product for more than 3 days and use only as directed. Side effects: General stimulation causing increased heart rate and blood pressure, insomnia, nervousness, anxiety, tremor, dry mouth, blurry vision, and headache. It may also cause an inability to urinate. Therefore, consult a physician if you have any history of cardiac disease, high blood pressure, anxiety, or urinary problems. Also, combining decongestants with other other-the-counter or prescribed medicines with similar side effects may lead to dangerous complications".

That's a long list of possible side effects simply from using a nasal spray with synephrine. Yet, you won't see the same warning on a weight loss product, which probably contains more synephrine than you can spray up your nostrils.
The FDA does not approve of the use of synephrine for the purpose of weight loss. To circumvent the FDA's authority, supplement manufacturers extract synephrine from a fruit called "bitter orange" (its peel is used in small amounts to make orange marmalade) so that their product will fall under the category of "dietary supplements" rather than drugs.

In Chinese medicine, bitter orange has been safely used for hundreds of years to make an herbal concoction called zhi shi as a digestive aid for upset stomach. So there should be no problem using bitter orange or synephrine in a weight loss pill, right? Wrong.

There is a big difference when an experienced herbalist uses the fruit, flower, leaf or root of an herb compared to when the active ingredient is extracted and used in much larger doses in pill or capsule form.

Consider this: Chinese herbalists use ma huang, which contains ephedrine to alleviate asthma sufferers. Ma huang has a good safety record when used for this purpose and in this manner. The adverse side effects began when the ephedrine in ma huang was used in concentrated form in diet pills.

Synephrine is chemically similar to ephedrine though it is not as potent. However, since it also constricts blood vessels and raises the heart rate, the concern is that in large doses, it may produce the same side effects of ephedrine namely irregular heartbeats, anxiety, high blood pressure, heart attack, and stroke.

A fact sheet on bitter orange from the Natural Medicines Comprehensive Database states that "the small amounts found in food have not been shown to be harmful, but larger amounts found in over-the-counter herbal supplements can be harmful". The fact sheet further warns, "The ingestion of large amounts of bitter orange peel in children can cause intestinal colic, convulsions, and even death."

The other concern is that just like ephedrine, the effects of synephrine are heightened or exaggerated when combined with another stimulant like caffeine. Manufacturers almost always package synephrine with caffeine because although synephrine has the same appetite-suppressing qualities as ephedrine, it lacks the energizing "kick" that ephedrine was famous for. To give their product an extra "zing", the addition of large amounts of caffeine is almost mandatory.

Consumer Reports, a non-profit organization that does independent reviews and analysis of supplements, sent a team of reporters to 90 stores and checked the Internet to analyze ephedra-free weight loss pills. They found that many products contain as much caffeine as six cups of strong coffee.

Another worry is that bitter orange, just like grapefruit, contains a natural chemical that can interfere with over-the-counter and prescription medication that a dieter may already be taking. Dr. Adriane Fugh-Berman of Georgetown University told Lauran Neergaard of the Associated Press that bitter orange contains a natural chemical just like grapefruit that allows certain medications to build up to dangerous levels.

In 1999, alternative medicine expert Dr. Andrew Weil of the University of Arizona wrote about the possible dangers of using bitter orange as a weight loss supplement in his website. "Results of one study that looked at the weight loss effects of bitter orange should serve as a cautionary tale. A group of Italian researchers published results showing that as the dose of bitter orange was increased, lab rats ate less and did lose weight but also developed heart abnormalities and died. The researchers speculated that the deaths were due to the stimulant action of the synephrine. These scientists cautioned that bitter orange may pose a danger, especially when used by the elderly, the obese and those with heart problems."

It is possible to a buy a weight loss product or "fat burner" that contains synephrine and/or caffeine and yet not see those ingredients listed on the label. That's because manufacturers may list other names or list only the herbs that the active ingredients are derived from. This can be deceiving because the average consumer may not know that what he or she is buying contains these things.

Synephrine may be listed as bitter orange, sour orange, green orange, Seville orange, neroli oil, zhi shi, or Citrus aurantium.

Caffeine, meanwhile, can be hiding under the names guarana, kola nut, green tea, mate, Paullina cupana, and mate.

Until the DSHEA or Dietary Supplement Health Education Act of 1994 is changed, the FDA will be at a loss to stop the market from being flooded with weight loss products containing ingredients that are not fully tested for safety or effectiveness. It is truly a "buyer beware" market.

To protect yourself, perhaps the best advice to take is that of Jamie Kopf, editorial associate at Consumer Reports, who told The Detroit Free Press, "Our baseline advice is to avoid all weight-loss products. It's a complete jungle out there. It's highly unregulated. There are all kinds of pseudonyms and products that sound safe, but, like ephedra, they have the same dangers. And there's little data showing these things work. Why take the gamble?".

Update: On April 14, 2005, the ban on ephedra products was lifted. Federal Judge Tena Campbell ruled that if the FDA wants to continue the ban, it will have to prove that products containing ephedra are dangerous at the doses recommended by manufacturers

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