Further analysis of the short-term inhibition of food intake in humans by the dipeptide L-aspartyl-L-phenylalanine methyl ester (aspartame)

Physiol Behav. 1991 Apr;49(4):739-43. doi: 10.1016/0031-9384(91)90312-c.


It was reported previously that the dipeptide sweetener aspartame suppresses food intake in humans by a postingestive action. The present study examined the hypothesis that this is due to an effect of phenylalanine, one of the primary breakdown products of aspartame (phenylalanine is a potent releaser of the so-called satiety hormone cholecystokinin, CCK). Capsulated aspartame (400 mg) administered to human volunteers reduced food intake by 15% (253 kcal) in a lunchtime test meal begun 1 hour later. However, neither phenylalanine (200 mg) nor the other constituent amino acid of aspartame, aspartic acid (200 mg), altered intake compared with placebo. Despite the large effect on food intake there were no treatment differences in pre- or postmeal ratings of motivation to eat. This suggests that aspartame may act to intensify the satiating effects of ingested food. Although high doses of phenylalanine reduce food intake, an individual action of phenylalanine cannot account for the potent anorexic effect of aspartame. In discussing alternative mechanisms it is noted that the amino acid sequence of aspartame (Asp-Phe) is the same as the C-terminal dipeptide of CCK. A direct action of aspartame at CCK receptors appears to be unlikely; however, aspartame might act as CCK releaser. Further studies are required to elucidate the mechanism of aspartame's anorexic action and perhaps to evaluate its therapeutic potential as an antiobesity agent.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Appetite / drug effects
  • Aspartame / pharmacology*
  • Aspartic Acid / pharmacology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Feeding Behavior / drug effects*
  • Female
  • Humans
  • Hunger / drug effects*
  • Male
  • Neural Inhibition / drug effects*
  • Phenylalanine / pharmacology
  • Satiety Response / drug effects*


  • Aspartic Acid
  • Phenylalanine
  • Aspartame