The World Health Organization defines obesity and overweight as the excessive accumulation of body fat and warns that both conditions pose serious threats to health by increasing the risk for chronic diseases like diabetes, cancer, and cardiovascular diseases. Effective methods to counter obesity include changes in lifestyle, such as engagement in physical activity and exercise, as well as controlling one’s weight through balanced dieting. Nevertheless, lifestyle modifications are not always easy to achieve. Therefore, scientists have called for effective antiobesity pharmacological treatments, or diet drugs. These drugs include both pharmacological and nonpharmacological agents that aid weight regulation by interfering with the processes of metabolism, reducing appetite, or influencing the absorption of calories or fat in the body. Pharmacological agents typically comprise substances that are purchased with medical prescription, whereas nonpharmacological agents refer to nonprescribed substances, such as dietary supplements and herbal products. While primarily intended to counter obesity, diet drugs are widely used by athletes and leisure-time exercisers to increase endurance, physical stamina, and leaner muscle mass. This entry presents an overview of commonly used diet drugs and addresses the potential role diet drugs play in weight control and athletic performance by focusing on their alleged health benefits and reported side effects.
Pharmacological Agents for Weight Loss
A wide range of diet drugs can be purchased in nutritional supplement stores, pharmacies, and through online retailers. However, regulatory authorities, such as the U.S. Food and Drug Agency (FDA), have only approved a handful of these substances. In professional sports, the World Anti-Doping Agency (WADA) and affiliated official sporting associations consider the use of diet drugs a doping practice.
Orlistat, sibutramine, and rimonabant are pharmacological agents used in dieting and weight-loss interventions. Orlistat is a gastric and pancreatic lipase inhibitor that aids weight control by reducing the absorption of dietary fat. Sibutramine is a monoamine reuptake inhibitor initially developed to treat depression. Unlike orlistat, sibutramine stimulates thermogenesis (the production of heat energy in the body) and acts in the human brain to increase satiety, which is the feeling that one is full. Rimonabant is a selective cannabinoid receptor antagonist that was approved in 2006 in Europe as an aid to exercise and weight-loss interventions. Clinical trials have shown that both orlistat and sibutramine are effective in weight loss, and their effects are increased if followed by lifestyle modification, such as exercising and dietary changes. There is limited evidence about the effectiveness of rimonabant in weight-loss interventions. However, following several reports about their side effects (e.g., increased cardiovascular risk, suicide ideation), sibutramine and rimonabant were suspended and withdrawn from the markets. Orlistat is the only currently licensed drug for dieting and weight-loss interventions.
Nonpharmacological Diet Drugs
Nonpharmacological diet drugs include herbal supplements with weight-loss properties and typically serve two purposes. They provide the body with nutrients that are scarce in low-caloric diets and stimulate weight loss. These supplements can be purchased over the counter and usually come in formulas or so-called proprietary blends containing vitamins, botanical derivatives (e.g., green tea, açai berry, guarana), caffeine, or even aspirin. Ephedrine is a well-known herbal diet drug and stimulant derived from the Chinese plant Ephedra sinica and was initially used for the development of amphetamine drugs. Several nutritional supplements contain ephedrine alkaloids. These supplements are assumed to counter obesity and increase athletic performance by stimulating thermogenesis. A meta-analytic study found that ephedrine use is associated with modest short-term weight loss, but there is no sufficient data to support the long-term effects of ephedrine on long-term weight loss and athletic performance. Most importantly, the concurrent use of ephedrine with others stimulants, such as caffeine, is associated with increased heart palpitations and psychiatric, autonomic, and gastrointestinal symptoms. Ephedrine was banned by the U.S. FDA in 2004 in response to consumer reports of adverse health effects, and is includedin the 2012 list of prohibited substances issued by WADA.
Ephedra-Free Diet Drugs
Following the ban on ephedra-based products, the nutritional supplements industry introduced alternative ephedra-free diet drugs. These supplements come in formulas or so-called proprietary blends. Bitter orange or Citrus aurantium is assumed to be an effective and safe alternative to ephedrine, and is a rich source of adrenergic amines synephrine and octopamine. Synephrine and octopamine are similar to norepinephrine, and their thermogenic effects are heavily advertised. Although related research is still growing, the safety of octopamine and synephrine was challenged by evidence showing that their effects on cardiac function are similar to that of ephedrabased supplements. While synephrine is not considered a doping substance, octopamine is included in WADA’s 2012 list of prohibited substances.
Dieting and weight management can effectively counter obesity. However, only a few pharmacological agents have been licensed for this purpose. Over-the-counter pharmacological and herbal-based dietary supplements with alleged health benefits and weight-control properties are easily accessible for individuals suffering from obesity, athletes, or leisure-time exercisers. Nevertheless, the safety of such products has either been challenged or still remains to be determined by empirical evidence. The development of regulation policies for diet drugs in professional sports is an ongoing and dynamic process.
- Ara, R., Blake, L., Gray L., Hernández, M., Crowther, M., Dunkley, A., et al. (2012). What is the clinical effectiveness and cost-effectiveness of using drugs in treating obese patients in primary care? A systematic review. Health Technology Assessment, 16(5). doi:10.3310/hta16050
- Boesten, J. E., Kaper, J., Stoffers, H. E., Kroon, A. A., & van Schayck, O. C. (2012). Rimonabant improves obesity but not the overall cardiovascular risk and quality of life; results from CARDIO-REDUSE (CArdiometabolic Risk reDuctIOn by Rimonabant: The effectiveness in daily practice and its use). Family Practice, 29, 521–527.
- Dwyer, J. T., Allison, D. B., & Coates, P. M. (2005). Dietary supplements in weight reduction. Journal of the American Dietetic Association, 105, 80–86.
- Greenway, F. L. (2001). The safety and efficacy of pharmaceutical and herbal caffeine and ephedrine use as a weight loss agent. Obesity Reviews, 2, 199–211.
- Padwal, R. S., & Majumdar, S. R. (2007). Drug treatments for obesity: Orlistat, sibutramine, and rimonabant. Lancet, 369, 71–77.
- Rossato, L. G., Costa, V. M., Limberger, R. P., Bastos, M.
- , & Remião, F. (2011). Synephrine: From trace concentrations to massive consumption in weight loss. Food and Chemical Toxicology, 49, 8–16.
- Shekelle, P. G., Hardy, M. L., Morton, S. C., Maglione, M., Mojica, W. A., Suttorp, M. J., et al. (2003). Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: A meta-analysis. Journal of the American Medical Association, 289, 1537–1545.
- Simpson, S. A., Shaw, C., & McNamara, R. (2011). What is the most effective way to maintain weight loss in adults? British Medical Journal, 343, doi: 10.1136/bmj.d8042