FDA Urged to Step Up Regulation of Supplements: Adverse events are largely underreported.

The days when the dietary supplements industry is allowed to regulate itself may be numbered following release of a federal report addressing growing concerns about dietary supplement industry.

The report, issued this month by the Government Accountability Office, calls on the Food and Drug Administration to expand adverse event reporting and increase its efforts to educate the public about the safety, efficacy, and labeling of these products. The GAO investigation into supplement safety was made at the request of Congress.

According to the 77-page report, the FDA should be tracking all levels of adverse events related to the use of dietary supplements and herbs, not just severe events. And, the report noted, despite the 2007 requirement for improved manufacturing practices, the FDA still lacks even the most basic ability to track the quality of dietary supplements (www.gao.gov/new.items/d09250.pdf).

Companies that manufacture the products are not required to identify themselves as such, or to provide the FDA with information about the products, including the product name and ingredients, the report said. And if a product is found to be dangerous, the agency is hamstrung—it can only ask for a voluntary recall as it did in December, when Star Caps, a popular weight-loss supplement, was found to contain prescription-strength levels of the diuretic bumetanide.

The FDA lost its authority to regulate the ingredients of dietary supplements prior to marketing with the enactment of the Dietary Supplement Health and Education Act of 1994 (DSHEA) (www.cfsan.fda.gov/∼dms/dietsupp.html). Prior to passage of the DSHEA, which went a long way toward deregulating the dietary supplement industry, the ingredients of dietary supplements were regulated under the 1958 Food Additive Amendments to the Federal Food, Drug, and Cosmetic Act.

Dietary supplements fall within the definition of complementary and alternative medicine (CAM). An earlier federal report issued by the Centers for Disease Control and Prevention found that use of CAM is widespread. For example, when patients with arthritis become frustrated by lack of pain relief, they often turn to dietary supplements.

The issue of quality control has bothered Dr. Roy Altman for years. Supplements and herbal preparations designed to promote joint health and relieve pain are some of the most popular products on the market, grabbing almost as big a market share as weight-loss products, he said in an interview. “We are looking at probably $40-$60 billion spent on over-the-counter arthritis supplements each year,” he said, but noted that “this is only a fraction of what is spent on prescribed arthritis medications.”

Some of these products probably do have a beneficial effect in patients with rheumatic disorders, said Dr. Altman, professor of rheumatology at the University of California, Los Angeles. The problem is identifying which products actually contain what the label promises, and nothing else. “We, and a group of colleagues from Canada, once tested 10 different glucosamine products sold in the U.S. Four of them didn't even have glucosamine in them, and of the remaining six, four had much less than was stated on the product label.”

Similar quality control problems led Congress to request the investigation about 18 months ago, said Lisa Shames, the GAO's director of Food Safety and Agriculture Issues. “There has been a lot of congressional interest into how FDA was implementing the requirements [for oversight of dietary supplements and herbal products], especially the requirement for reporting adverse events,” she said in an interview.

One of the paper's key findings is that adverse events are probably significantly underreported, she said. In December 2007, the FDA began requiring manufacturers of dietary supplements and herbal preparations to report all serious adverse events related to the use of their products. “Since then, FDA has had a threefold increase in the number of events reported, but the big question is whether this is all the events that are happening,” Ms. Shames said. From January through October 2008, the FDA received 948 reports of adverse events, compared with 298 over the same time frame in 2007. “FDA recently estimated that the true number of adverse events could be well over 50,000 each year. We recommended that the FDA require reporting of all adverse events, regardless of their severity.”

The report also called on the FDA to require more information from manufacturers about the ingredients in their products.

Also, under current law, manufacturers are the ones to decide whether an ingredient is “generally recognized as safe,” and thus exempt from the laws that govern pharmaceutical products, she said. The report asks that the FDA take part in this responsibility, by clarifying the evidence needed to document an ingredient's safety and the methodology necessary to establish that safety.

The agency should also increase its efforts to educate the public about the safety of supplements, the report concluded. “People think all these products are safe and approved by the FDA, and of course, this isn't the case,” Ms. Shames said.

The report didn't even touch on manufacturing issues, which are controlled by a set of laws that until recently left manufacturing oversight to the companies, with little government regulation. In 2007, the FDA finalized its Good Manufacturing Practice regulations, which will require quality control measures for all domestic manufacturers and foreign manufacturers that distribute in the United States. But the law is being phased in by company size, with the smallest companies having until June 2010 to come into full compliance.

Dr. Altman noted that country of manufacture is not a good guideline. “You might think you are better off buying something that was made in the U.S., but in reality a lot of those are manufactured in China and then repackaged in the U.S.”

Dr. David Riley, founder of the Integrative Medicine Institute in Santa Fe, N.M., pointed to a study in which researchers obtained 190 Ayurvedic medicines from China and India through Internet sources and determined their components by x-ray fluorescence spectroscopy. They found that 20% contained some level of toxic metal (lead, mercury, or arsenic). U.S.-manufactured products were just as likely to be contaminated as were those made in India (22% vs. 19%). Among companies manufacturing the metal-containing products, 75% claimed that they adhered to the FDA's Good Manufacturing Practices (JAMA 2008;300:915-23).