More than half of U.S. adults are overweight or obese, and more than one- third of U.S. adults are trying to lose weight. Increasingly, they are turning to weight loss supplements for help. The most widely used weight loss supplement is ephedra, or ma huang. The active ingredients in ephedra— ephedrine alkaloids—are compounds with potentially powerful stimulant effects on the nervous and cardiovascular systems. The dietary supplement industry estimates that as many as 3 billion servings of ephedra are sold each year in the United States and approximately 12 million individuals were using ephedra in 1999. FDA regulates dietary supplements under DSHEA, which covers vitamins, minerals, herbs or other botanicals, amino acids, certain dietary substances, or derivatives of these items. A product that contains any active ingredient not on the preceding list—such as synthetic ingredients that are sold in over-the-counter drugs and prescription medications—may not be marketed as a dietary supplement. DSHEA requires that dietary supplement labels include complete lists of ingredients and the amount of each ingredient in the product. Products may be labeled as “proprietary blends” and must list all ingredients but do not need to list the amount of each ingredient. In addition, dietary supplements cannot be promoted as a treatment, prevention, or cure for a specific disease or condition. To the extent that therapeutic claims are made, FDA may take action. FDA generally oversees the safety of dietary supplements. It may issue a regulation, for example, to prevent the further marketing of dietary supplements that it has determined pose an unreasonable risk of illness under the recommended conditions of use. A dietary supplement may also be removed from the market if HHS finds that it poses an imminent hazard to public health and safety. However, under DSHEA, it is the manufacturer who is responsible for ensuring the safety of the weight loss supplements it sells. Dietary supplements do not need approval from FDA before they are marketed. DSHEA does not require manufacturers to register with FDA, identify the products they manufacture, or provide reports of adverse events—harmful effects or illnesses—to FDA. However, FDA is authorized to issue regulations governing GMPs to standardize manufacturing, packaging, and holding practices. Since manufacturers of dietary supplements are not required to provide reports of adverse events to FDA, the agency and others rely on voluntary postmarketing reporting of adverse events to better understand the safety of dietary supplements. In addition to these adverse event reports, FDA uses data from poison control centers, reports and inquiries from consumers and health care providers, and complaints from trade competitors to track potentially dangerous supplements. These reporting systems can then be used to signal safety concerns. There are numerous problems with this passive system of adverse event reporting, and these have been noted extensively in our earlier work. For example, only a small proportion of adverse events are reported, and those reports often are incomplete or contain inconsistent information. In an effort to control unfair or deceptive acts or practices in the marketplace, FTC oversees dietary supplement advertising to ensure that product claims are truthful and substantiated. Manufacturers and distributors of weight loss supplements make a wide variety of claims about how their products work. They claim that the supplements reduce appetite or cravings, increase metabolic rate, have a laxative effect, and block digestion of fat, carbohydrates, sugars, or starches. Manufacturers frequently combine multiple supplements into single products, promoting several pathways to weight loss. FTC can demand that false, exaggerated, or unsubstantiated claims be removed from advertising, and it also can seek monetary relief for injurious conduct. The marketing of unsafe products or potentially dangerous products without adequate safety warnings could violate the Federal Trade Commission Act. Federal research regarding the safety and efficacy of weight loss supplements marketed to the public is carried out under NIH sponsorship. The agency’s NCCAM is primarily responsible for federal research on complementary and alternative medicine, including dietary supplements, although other NIH institutes may also fund such research. Generally, NCCAM funds clinical trials to evaluate the safety and efficacy of popular alternative medicine products and therapies of interest. NIH’s Office of Dietary Supplements (ODS) supports research and disseminates research results in the area of dietary supplements. Specifically, ODS plans, organizes, and supports conferences, workshops, and symposia. Although ODS can initiate such activities, it generally works in conjunction with other NIH institutes and centers and other groups. States and individuals can also take action against manufacturers of weight loss supplements. States can enact and enforce laws and regulations to protect consumers from dangerous weight loss supplements and false or misleading advertising. Individuals can file lawsuits against manufacturers alleging injury from using weight loss supplements. There is little evidence on whether weight loss supplements are efficacious. However, we identified several ways that weight loss supplements might cause health risks. Many weight loss supplements have been associated with side effects, some of which can be serious. Some weight loss supplements should be avoided by individuals with certain medical conditions because particular effects of the supplements could exacerbate the conditions. In addition, some weight loss supplements have potentially dangerous interactions with prescription or over-the-counter medications or foods. Further, a supplement may contain dangerous contaminants or different amounts of an active ingredient than indicated on the product label. Finally, we found multiple-ingredient products to be of particular concern because of the increased difficulty involved in evaluating and understanding their safety. For most weight loss supplements, little scientific evidence to date supports their efficacy. Although there have been studies on specific ingredients, many of these studies have been of short duration, involved small numbers of individuals, or used study approaches that limited the usefulness of their findings. There have been few comprehensive reviews or long-term studies of efficacy. One comprehensive review of alternative treatments for weight loss found no reliable scientific evidence for the efficacy of any of the weight loss supplements that it reviewed. Another review found similar results except for ephedra. Most of the research that has been done to evaluate the efficacy of weight loss supplements has involved ephedra. A recently published randomized study found that a combination of ephedra and kola nut (a source of caffeine) promoted weight reduction. Other smaller studies have shown similar results for ephedra. Available research on weight loss supplements, though limited, in general suggests that some supplements are associated with both minor and potentially serious adverse effects. Further, many supplements are contraindicated for individuals with some underlying health problems. That is, there are specific dangerous side effects for persons with certain health conditions. In addition, a variety of weight loss supplements can have dangerous interactions with prescription and over-the-counter drugs that are being taken concurrently. However, just as with research on efficacy, few systematic studies exist on the negative health consequences of particular weight loss supplements. Adverse effects, contraindications, and interactions that have been associated with some of the more commonly used weight loss supplements are shown in the appendix. The side effects associated with weight loss supplements are generally mild and may include unpleasant digestive symptoms, insomnia, or rash. However, for some supplements there may be more serious adverse effects. For example, dehydroepiandrosterone (DHEA) may increase the risk of some hormone-related cancers. Both aloe taken internally, such as in a dieter’s tea, and chromium may also increase the risk of cancer. FDA has identified illnesses and injuries reported to be associated with the use of selected weight loss supplements, including yohimbe, which has been associated with renal failure, seizures, and death, and ephedra, which has been associated with seizures, heart attacks, psychosis, stroke, and death. Use of some weight loss supplements has been found to be contraindicated, or inadvisable, for persons with certain preexisting medical conditions. For example, bitter orange (Citrus aurantium) should be avoided by persons with certain heart conditions. DHEA may worsen prostate hyperplasia. Neither herbal laxatives found in dieter’s teas nor fiber should be used by persons with intestinal obstructions. Fiber and gymnema may affect persons with diabetes. These risks are of particular concern because serious health conditions, such as hypertension and diabetes, often go undiagnosed. Consumers who have undiagnosed medical conditions and inadvertently use contraindicated dietary supplements may expose themselves to considerable risk. Using weight loss supplements along with certain prescription medications and certain foods poses an additional risk. For example, fiber may alter the effects of some medications. Other supplements, such as DHEA, may duplicate the effects of prescription medications. Similarly, aloe and chromium affect blood sugar levels and may require altering the dosage of medication for diabetes. And many supplements, such as fiber, green tea, and guggul, may alter the effects of anticoagulant medications. Yohimbe and St. John’s wort should not be used with certain foods (such as red wine, liver, and cheese) because they may cause a toxic reaction, and chitosan may affect the absorption of certain vitamins. The possibility of such interactions is of particular concern because it has been reported that more than 18 percent of those who use a prescription drug also use a dietary supplement, and further, about 60 percent of people who use dietary supplements do not discuss their supplement use with their doctors. Contaminated supplements and those with different amounts of active ingredients than indicated on the labels, or different active ingredients altogether, can pose significant health risks to consumers. Research has found supplements contaminated with pesticides or heavy metals, some of which are probable carcinogens and are toxic to the liver and kidneys. One commercial laboratory found contamination in samples of the weight loss supplements St. John’s wort and chromium. For dietary supplements in general, the same laboratory found that 24 percent of the 62 herbal products it tested, particularly those containing ginseng, and 4 percent of the 68 nonvitamin, nonmineral supplement products it tested were contaminated in some way.