Trouble with ephedra
When the wildly popular drug combo phen-fen was pulled from the market in 1997, people were forced to look elsewhere for weight-loss help. Many turned to a then-mysterious Chinese herb known as ma huang.
The natural supplement, commonly known as ephedra, seemed less risky than the prescription medicines, which had been linked to heart valve problems. But now the federal government is reviewing the supplement’s safety, and one manufacturer of ephedra is under criminal investigation by the Justice Department. Once again, many consumers are searching for a safe alternative.
Although supporters contend that ephedra is safe, some major sellers already are scaling back or abandoning sales of products containing the herb.
The maker of one of the most popular supplements, Ripped Fuel, said last month that it will discontinue it and other ephedra products.
Dietary supplement giant Herbalife has begun phasing out its three ephedra products and is instead promoting a new ephedra-free line of supplements.
General Nutrition Centers, the largest retailer of dietary supplements, announced Nov. 6 that it will request proof of age from customers purchasing products with ephedra to stop sales to minors.
The moves follow several months of particularly bad publicity. Although ephedra may indeed help the body burn fat -- it’s known as a thermogenic aid, meaning it raises metabolism and increases heart rate -- that weight-loss potential may come with a risk. Some studies have linked use of the herb to stroke, heart attack, seizures and sudden death. The Food and Drug Administration says it has received more than 1,200 reports of adverse events linked to ephedra, although supplement makers say the health problems could have occurred even if people hadn’t taken ephedra.
Growing concern over the safety of ephedra prompted the Bush administration, in June, to order a scientific review of the herb. Two months later, the Justice Department announced it was conducting a criminal investigation to probe whether a major manufacturer of ephedra, Metabolife, lied about the safety of its products.
“Ephedra is getting a very bad name, even though a definitive review of the safety of ephedra hasn’t been published,” said Mark Blumenthal, executive director of the American Botanical Council, a nonprofit educational and research organization. “It’s the 900-pound gorilla that is getting all the attention.”
Manufacturers trace their flagging support for ephedra to consumer unease about the herb’s safety, the rising costs of liability insurance and the threat of a possible government crack-down. It doesn’t hurt that they also seem to have found a promising alternative, one known by the healthy-sounding name “bitter orange.”
Bitter orange, or Citrus aurantium, is emerging as the central ingredient in a new generation of herbal weight-loss products. Both Twinlab and Herbalife announced the demise of their ephedra products at the same time they introduced those containing Citrus aurantium. Several other supplement makers also have launched ephedra-free formulations containing bitter orange, including Xenadrine EFX and TurboTrim Plus Ephedra Free.
“We’ve been happy with the [ephedra] products. They’ve worked very well. But, basically, it’s the media attention and the FDA circling around. We’ve decided to go the high road,” said Dr. Jamie McManus, senior vice president of the Herbalife medical advisory board. The company is introducing an ephedra-free formulation called Total Control.
But some experts say exchanging ephedra for Citrus aurantium may not protect consumers from harm or manufacturers from controversy. Because the herb is chemically similar to ephedra, it could cause similar health problems, they warn.
Although several supplement companies say they’ve tested Citrus aurantium, the results of that research have not been published or peer-reviewed for scientific validity. The studies that have been published have been small; one 1999 U.S. study of 23 people showed those taking Citrus aurantium for six weeks experienced a decrease in body fat of about 6 pounds.
“It’s a new kid on the block. But we don’t know if it’s a good kid or a bad kid,” said Bill Gurley, a professor of pharmaceutical sciences at the University of Arkansas. Manufacturers “really don’t have to do any research before putting these things on the market. So how do you really know if they’re safe?”
Citrus aurantium is made from the immature fruit of a plant known in various parts of the world as bitter orange, sour orange or Seville orange. In China, the fruit is known as zhi shi and is used in traditional Chinese medicine to relieve chest congestion and indigestion. Its active substance, synephrine, is chemically similar to ephedra, and both are considered thermogenic weight-loss aids.
“The two work much the same way. Citrus aurantium will boost metabolic rate and, indirectly, cause the breakdown of fat,” said Dennis Jones, a Vermont scientist who began working on Citrus aurantium 10 years ago and created the brand called Advantra Z.
Some herb makers say that bitter orange will work as well as ephedra but without affecting the central nervous system or the heart. “It has the same effects in the periphery of the body, but it’s weaker,” said Jones. “It’s nowhere near as potent.”
Gurley agrees that Citrus aurantium by itself probably has little effect. But herbal weight-loss products are typically mixtures of various herbs, such as caffeine to boost metabolism and herbs that act as diuretics. Blending several herbs typically increases effectiveness. In the same manner, mixing Citrus aurantium with other herbs may improve its potency, making it more effective and, potentially, more dangerous to some users, he said.
“I think you’ll see the same types of problems as ephedra,” he said. “Normally, synephrine is not well-absorbed in the gastrointestinal tract. But there are compounds in some of these products that could aid absorption.”
For example, Gurley said, the herbs guarana and green tea have the potential to exacerbate the activity of Citrus aurantium.
Another potential problem with Citrus aurantium is that it could interact with a host of prescription drugs, said Gurley, who is studying the herb. Citrus aurantium inhibits an enzyme, known as CYP3A4, in the small intestine that can alter the metabolism of drugs, boosting their activity.
“We know this enzyme is responsible for the metabolic activity of 50% of all prescription medications,” he said. “We know that Seville orange juice can wipe out those enzymes. It would be reasonable to think that these concentrated extracts would do the same.”
Both Jones and McManus said the studies they’ve seen, performed at McGill University in Montreal and by Herbalife, have not shown any side effects.
But until more is known about Citrus aurantium weight-loss products, however, Gurley urges caution. “It’s like where we were six years ago with ephedra.”
In the meantime, whether the federal government pulls ephedra off the market -- as the American Medical Assn. recently urged -- remains to be seen. The safety report ordered by the Bush administration is due out early next year and could help government and industry leaders reach a consensus on how to best regulate ephedra. The Rand Corp. of Santa Monica is developing the report.
“That report is going to be the defining word, or something close to it,” Blumenthal said. “I think the Rand report constitutes a very good development in the saga of ephedra because it’s an independent review.”
Leaders in the supplement industry continue to defend ephedra’s safety when taken by healthy individuals in the recommended doses. Industry representatives are working with the FDA to create labeling for all ephedra products that would state proper dosage and which individuals should avoid taking the herb, said Michael McGuffin, president of the American Herbal Products Assn., a national trade organization for the herb supplement industry.
But, Blumenthal notes, some herb supplement makers feel the entire herbal field is being dragged down by the safety questions surrounding ephedra.
“Some companies do not sell ephedra and don’t care if it’s regulated into a corner or removed from the market,” he said. “They just want to see the problem go away because they see the constant negative attention as being ultimately deleterious to the entire industry.”
