Diet Pills: It’s Still Buyer Beware

With some half of the adult U.S. population overweight–many individuals severely so–is it any wonder that the fastest growing segment of the dietary supplement industry is weight-loss aids? Since 1997, sales of diet pills and related supplements have been increasing 10 to 20 percent annually to the point where last year they reached $2 billion.

The biggest sellers continue to be products based on ephedra, or ma huang, a Chinese herb from the Ephedra sinica. Although the Food and Drug Administration has logged at least 1,173 “adverse event” reports among users of such products, “as many as 3 billion servings of ephedra are sold each year in the United States,” notes Janet Heinrich of the General Accounting Office, an investigational watchdog agency of the U.S. Congress.

Many consumers assume that such products have met some type of basic safety or efficacy standards before hitting the marketplace. However, as Heinrich pointed out in July 31 Senate testimony, federal regulators actually have limited oversight of such products and to date have “focused more on marketing than on safety.”

In fact, her agency found, “little is known about whether weight loss supplements are effective,” she said. Studies have been conducted using specific ingredients found in many diet products, she noted. However, most such studies were brief, exposed small groups of individuals, or adopted study approaches that limited the value of their findings, she said.

Of the studies published, most involved ephedra, a compound banned by Canada and several state governments. Though side effects and undesirable interactions with other commonly taken drugs have been reported for many diet supplements, Heinrich reported that her reviewers found that “few systematic studies exist” on complaints associated with specific products.

Moreover, it is not uncommon to find that amounts of a product’s active ingredients do not match what’s been reported on the label. The GAO investigators cited one ephedra study that found concentrations in one product were more than 50 percent higher than labeled; one chromium product studied elsewhere provided less than 5 percent of the amount claimed by its label.

An even bigger concern, Heinrich said, was the common finding that products contained ingredients not listed in the packaging. Earlier this year, she notes, the International Olympic Committee found that of 634 nutrition products that it analyzed, 15 percent contained ingredients banned by the committee and not listed on the label.

Regulating the marketplace

Drugs or new agricultural chemicals, such as pesticides, may not be sold in the United States until a manufacturer has established to the appropriate regulatory agency that the product is safe and effective.

Not so with dietary supplements. Seen as an offshoot of the food industry–indeed, many of the first entrants were food-derived natural products–dietary supplements can be sold without efficacy or safety studies as long as they contain ingredients already in the food supply.

FDA’s authority for regulating these goods is primarily limited to reining in exaggerated claims about functions or benefits. Product labels and advertising, for instance, can’t claim that a product cures or prevents disease. Rather, it can only say, for instance, a product contains one or more ingredients that come from foods that have been associated with good heart health or that a primary ingredient has been associated with some function–such as quenching of free radicals–that may underlie chronic ailments, such as cancer and heart disease.

At the Senate hearing, Joseph A. Levitt, director of FDA’s Center for Food Safety and Applied Nutrition, reported that he recently conducted a yearlong review of how his agency was implementing the Dietary Supplement Health and Education Act (DSHEA), the law outlining what his agency can do.

During this review, he said, FDA met with stakeholders–such as consumer groups, manufacturers, and scientists. All agreed that “safety first” should be the guiding principle, he reported. A cornerstone to such safety should be improved monitoring of reports identifying adverse effects, he maintained.

Unfortunately, noted Michael F. Mangano, Principle Deputy Inspector General for the U.S. Department of Health and Human Services (HHS)–FDA’s parent agency–”our review of the adverse-event reporting system for dietary supplements disclosed that it is an inadequate safeguard to consumers.”

Poor reporting of problems

If there were a means to glean and assemble into a single database most of the reports of problems associated with a diet aid or other food supplement, regulators and physicians might discern worrisome trends early and pull dangerous products from the marketplace. However, Mangano explains, “reporting adverse events associated with dietary supplements is entirely voluntary.” As such, he pointed out, there is no one-stop-shopping for such data as there is for drugs.

He reported at the hearing, for instance, that although the nation’s network of poison control centers received some 13,000 adverse reports on dietary supplements in 1999 alone, FDA received a mere 460. Moreover, Mangano noted, not only do hospitals, physicians, and consumers pass along few such reports to FDA, but the data they send are often incomplete.

FDA has at times attempted to follow up on health complaints linked to diet products. In a third of the cases, however, it was unable to get lists of all the ingredients in a product, Mangano reported. In 77 percent of the adverse reports for diet supplements, even such basic information as a product’s labeling was absent. In more than two-thirds of the instances where FDA requested a sample of the supplement described in a report, none was provided. Speculates Mangano, “Consumers may have discarded the remaining product, may want to hold on to it pending legal action, or may have sent it back to the manufacturer for a refund.”

Further impeding follow-up, he found, FDA couldn’t even identify who made 32 percent of the products cited in adverse reports or find addresses for 70 percent of the manufacturers.

At the hearing, Mangano recommended that FDA seek greater authority: to make manufacturers report all serious adverse affects; make manufacturers register their products with the agency; and develop a database that tracks adverse events associated with dietary supplements. He also recommended that FDA be included in the reporting network now maintained by the nations’ poison-control centers.

The case against ephedra

The Senate subcommittee launched its investigatory hearing to learn more about dietary supplements in general–and ephedra in particular. Not only are products containing ephedra big players in the diet arena, but they have also raised big health concerns.

Eight years ago, FDA published a bulletin asking physicians to contact the agency with any evidence of side effects from their patients’ use of botanical dietary supplements marketed as dieting aids, all-natural energy and performance enhancers, and body builders. These products were flying off store shelves. However, FDA was becoming bombarded with reports of adverse reactions that ranged from dizziness and elevated blood pressure to seizures, stroke, psychosis, and death.

Most troubling were the growing complaints about ephedra–a powerful stimulant chemically related to epinephrine, or adrenaline, a flight-or-fight hormone that the body produces under stress. Ephedra was usually delivered along with a hefty dose of caffeine, another stimulant that constricts blood vessels.

FDA was accumulating so many serious complaints about ephedra products that by 1999, it solicited a comprehensive review of them. Christine A. Haller and Neal L. Benowitz of the University of California, San Francisco took up the challenge and sifted through 140 reports. At least 31 cases “were considered to be definitely or probably related to the use of supplements containing ephedra alkaloids, and 31 percent were deemed to be possibly related,” they reported in the Dec. 21, 2000 New England Journal of Medicine.

In some cases, seemingly healthy people suffered a stroke or heart attack after taking over-the-counter ephedra products as directed. Others experienced seizures, insomnia, personality changes, and permanent nerve damage. These reports included 10 deaths, including one in a newborn and another in a fetus. It’s not clear whether some underlying sensitivity or physical characteristics resulted in certain individuals facing an unusual vulnerability.

It appeared that risks from the supplement were “difficult to justify because the alkaloids have no demonstrated benefit,” Haller and Benowitz said.

In a related editorial, G. Alexander Fleming of Ingenix Pharmaceutical Services argued that the report by Haller and Benowitz points to “a loophole that was created by Congress with the passage of DSHEA. This act allows inadequately tested drugs to be marketed as ‘dietary supplements’–an innocuous and even holistic-sounding term.” In fact, he argues, although there are true dietary supplements on the market, such as vitamins, any compound containing ephedra “should not be called a dietary supplement; it is a drug.”

Abuse of these products could be dramatically limited, Fleming contended, if they were simply called drugs–and regulated as such.

That hasn’t happened, nor was there any serious call for that at the recent Senate hearing–other than by Karen Ruiz, a young San Clemente, Calif., mother who in 1996 ended up in the psych ward of a local hospital within a week of taking an “all-natural” herbal product being touted to increase energy, physical endurance, and weight loss. It contained a large quantity of ephedra to be taken along with a caffeinated chaser.

Eventually, Ruiz sued the laboratory that manufactured the product and settled out of court. As she testified at the hearing, the manufacturer and the marketer both hired lawyers to fight her–”and we did not have the financial capability, or endurance, to fight this giant. The money we received was just enough to cover our medical bills and replenish our small savings.”

Since then, she’s seen plenty of related ephedra products on grocery and convenience-store shelves. “Never do I see posted warnings,” she said. In fact, she puzzled, since FDA banned nonprescription synthetic ephedrine and caffeine products in the 1980s, “Why is the herbal equivalent allowed on the market?”

She pleaded with lawmakers at the hearing to make manufacturers prove their products’ safety prior to marketing.

Industry relies on big government

At the same hearing, Michael McGuffin, president of the national trade group called the American Herbal Products Association, noted that his industry has developed a number of voluntary standards to “promote responsible commerce in botanicals.” Indeed, he argued that his industry remains “ahead of federal regulatory agencies with respect to encouraging the herbal supplement industry to label their products with useful and important information.”

Enforcing good practices remains the challenge, he said, because “there is a limit . . . to what any trade association can do to separate out bad products or bad actors.” To keep renegades in line, he said, “we rely on the ‘big stick’ of the federal enforcement agencies.”

Toward that end, he noted that his organization has begun warning its members that they will soon have to register with the feds as part of new anti-terrorism legislation. Under the Public Health Security and Bioterrorism Preparedness Response Act, signed into law on June 12, they, like all other food manufacturers, processors, packers, or holding companies, must register with the HHS Secretary.

Indeed, he noted that many of his association’s members have been quite proactive about safety issues, such as lobbying in 1996 that druglike food-supplement products be subject to rules enacted under the Controlled Substances Analogue Enforcement Act of 1986. It took FDA another 4 years to take even “limited” action in this arena, McGuffin said.

Yet Heinrich noted that even where federal agencies have the authority and willingness to take action against companies that violate some law, action has seldom been swift and successful.

For instance, she pointed to a 2000 Federal Trade Commission ruling against Enforma Natural Products for a pair of its herbal preparations: “Fat Trapper” and “Exercise in a Bottle.” Enforma advertising claimed that with these products “you can eat what you want and never, ever, ever have to diet again.” Although the company agreed to a $10 million settlement for its deceptive claims, Heinrich notes that “in 2002, the company was still marketing the products in question.”

What’s a consumer to do?

With so little known about the efficacy and risks of diet aids, research must become a priority, Heinrich said. And she noted that at the behest of Congress, the National Institutes of Health’s Office of Dietary Supplements has finally begun investigating the safety and utility of diet supplements, especially ephedra. Some findings should be available this fall, she says.

The National Institute of Environmental Health Sciences and National Toxicology Program has also launched research on weight-loss supplements in animals, she noted. Finally, the Office of Dietary Supplements is working with the National Heart, Lung, and Blood Institute to develop a workshop on weight-loss supplements. The plan is to review the science and identify research gaps.

In the meantime, the Federal Trade Commission is directing a program known as Operation Waistline aimed at alerting consumers to misleading and deceptive weight loss claims, steering them to accurate information about healthy weight loss, and bringing legal action against companies that violate the law.

As part of its educational outreach, the FTC also maintains a glitzy and persuasive Web site seemingly for a Scandinavian herbal formula called NordiCaLite that shrinks fat cells. It promises the product will help you shed 30 pounds in 30 days. It even has a hotlink for ordering the product. But selecting that link actually brings up a disheartening message: “NordiCaLite is not a real weight-loss product. If you respond to an ad like this one . . . YOU COULD GET SCAMMED!!!”

The Web page goes on to explain that the ad is a fake, posted to raise awareness about the false and deceptive advertising claims made by many “weight-loss” products.

At the end, it advocates what overweight people least want to hear: that to maintain weight loss, people must change how they eat and must increase exercise. Elsewhere on the FTC’s site are links to the Weight-Control Information Network. This NIH program was established to help individuals find plenty of sensible and effective tips to healthy slimming.