Diet Drugs

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.


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