Ephedra-free weight-loss supplements scrutinized
Only months after the herb ephedra was pulled from the market, government regulators and scientists have become increasingly alarmed about a new generation of herbal weight-loss products -- specifically those containing bitter orange.
Like ephedra, the stimulant is used by people seeking to lose weight. Products containing the ingredient only have been widely available for a little more than a year, but already bitter orange has been linked to 169 reactions in people who took it, said a spokeswoman for the Food and Drug Administration.
The agency is monitoring reports of problems with such ephedra-free products closely and is planning studies to explore their safety, she said.
Industry observers are watching the issue with interest. “I think [the FDA] learned their lesson with ephedra, so maybe they’re going to be more cautious with these first cousins,” said Bill Gurley, a professor of pharmaceutical sciences at the University of Arkansas. “How quickly they’ll act, that’s the key question. But at least they are looking at it.”
A government ban on ephedra went into effect April 12 after years of reports and studies on its potential dangers. About 16,000 adverse events and numerous deaths had been linked to the substance, and the agency was criticized widely for not taking action sooner.
Although the FDA maintains that so-called adverse events are not considered proof of a problem, dietary supplements that garner suspicion now may be targeted for faster action.
Several lawmakers have already asked the FDA to investigate the safety of ephedra substitutes and to remove dangerous products. And Sen. Richard Durbin (D-Ill.), who has expressed concern over bitter orange, is working with Sen. Orrin G. Hatch (R-Utah), a longtime supporter of the dietary supplement industry, to introduce a bill mandating that manufacturers promptly report serious adverse events related to dietary supplements.
The action by lawmakers and the FDA’s interest in funding studies on ephedra-free products follows growing unease over bitter orange, the most prominent ingredient in most ephedra substitute products. The herb -- Citrus aurantium, also called sour orange, Seville orange or zhi shi -- has a long history of use in Chinese medicine but only came to the attention of American consumers as fears over ephedra grew.
Extracts from the peel of the bitter orange contain a chemical called synephrine, a substance similar to ephedra and pseudoephedrine, which is found in many over-the-counter cold remedies. Like ephedra, bitter orange may contribute to weight loss by increasing metabolism.
But while ephedra raises heart rate, respiratory rate and blood pressure, it is unclear whether bitter orange acts similarly. Some animal studies suggest similar effects, which could make the herb particularly risky for people with arrhythmias and high blood pressure.
Michael McGuffin, president of the American Herbal Products Assn., an industry trade organization, said products with bitter orange and caffeine (also a stimulant) were only a potential risk in people who should avoid stimulants in general, such as people with heart problems.
But, he said, “there is also interest in the industry in adding to the weight of the science on bitter orange. We’re going to have to provide a greater level of scientific data to the [FDA] and appease their concerns.”
Currently, there is little high-quality, scientific information on the substance’s risks and benefits. Scientists now are scurrying to learn more about its safety and effectiveness.
“It’s almost like we’re back to square one in understanding what these weight-loss products mean,” said Dr. Christine Haller, a medical toxicologist at UC San Francisco who is studying bitter orange.
Determining the safety of bitter orange and other ephedra-free products may be complicated because most contain multiple ingredients, such as bitter orange, caffeine and other herbs, Gurley said. He’s about to start a study examining heart rate, blood pressure and the heart’s electrical activity in people taking a product containing bitter orange and caffeine.
“What we do know about synephrine is that, pharmacologically, it’s similar to ephedra,” he said. “Ephedra and caffeine boost each other’s side effects. By themselves, they’re fairly innocuous.”
Haller, a consultant for the California Poison Control Center, is comparing the effects of a bitter orange extract, a multiple-ingredient supplement containing bitter orange and a placebo. She said the agency had received some reports of agitation, nervousness and high blood pressure related to bitter orange products.
A few reports of serious problems related to the herb also have been published, including a case in the March issue of Annals of Pharmacotherapy describing a heart attack in a 55-year-old woman who had taken 300 milligrams a day of bitter orange in a product called Edita’s Skinny Pill.
The woman had no history of heart disease, high blood pressure or high cholesterol, but she did smoke, a risk factor in heart attacks.
“We don’t have any clinical studies in humans to rely on,” Haller said. “You really need to have some data. I appreciate [the FDA’s] desire to act quickly, but you have to have some evidence that it induces harm.”
Added Gurley: “We’re really behind the eight ball.... A lot of these [ephedra-free] products have been out there for a year, and it may take another year to see more effects.”
Both health and business concerns are at stake. According to the Nutrition Business Journal, a San Diego-based industry publication, about two-thirds of ephedra users switched to an ephedra-free product after the FDA crackdown. At one time, ephedra sales totaled well over $1 billion a year in the United States.
But supplement makers are wary of “another ephedra” controversy and wish to work with the FDA on any safety concerns, McGuffin said. The industry supports the proposed bill to mandate manufacturers’ reporting of serious adverse event, he adds.
“There ought to be a mandatory system,” McGuffin said.
