Physiological mechanisms mediating aspartame-induced satiety

Physiol Behav. 2003 Apr;78(4-5):557-62. doi: 10.1016/s0031-9384(03)00034-9.


Aspartame has been previously shown to increase satiety. This study aimed to investigate a possible role for the satiety hormones cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) in this effect. The effects of the constituents of aspartame, phenylalanine and aspartic acid, were also examined. Six subjects consumed an encapsulated preload consisting of either 400 mg aspartame, 176 mg aspartic acid+224 mg phenylalanine, or 400 mg corn flour (control), with 1.5 g paracetamol dissolved in 450 ml water to measure gastric emptying. A 1983-kJ liquid meal was consumed 60 min later. Plasma CCK, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucose, and insulin were measured over 0-120 min. Gastric emptying was measured from 0 to 60 min. Plasma GLP-1 concentrations decreased following the liquid meal (60-120 min) after both the aspartame and amino acids preloads (control, 2096.9 pmol/l min; aspartame, 536.6 pmol/l min; amino acids, 861.8 pmol/l min; incremental area under the curve [AUC] 60-120 min, P<.05). Desire to eat was reduced from 60 to 120 min following the amino acids preload (control, -337.1 mm min; aspartame, -505.4 mm min; amino acids, -1497.1 mm min; incremental AUC 60-120 min, P<.05). However, gastric emptying rates, plasma CCK, GIP, insulin, and glucose concentrations were unaffected. There was a correlation between the increase in plasma phenylalanine and decrease in desire to eat after the liquid meal following the constituent amino acids (r=-.9774, P=.004). In conclusion, it is unlikely that aspartame increases satiety via CCK- or GLP-1-mediated mechanisms, but small changes in circulating phenylalanine concentrations may influence appetite.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Appetite / drug effects
  • Aspartame / pharmacology*
  • Aspartic Acid / blood
  • Aspartic Acid / pharmacology
  • Blood Glucose / metabolism
  • Cholecystokinin / metabolism
  • Cross-Over Studies
  • Diet
  • Female
  • Gastric Emptying / drug effects
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1
  • Hormones / blood
  • Humans
  • Insulin / blood
  • Male
  • Peptide Fragments / metabolism
  • Phenylalanine / blood
  • Phenylalanine / pharmacology
  • Protein Precursors / metabolism
  • Satiety Response / drug effects*
  • Satiety Response / physiology*
  • Sweetening Agents / pharmacology*


  • Blood Glucose
  • Hormones
  • Insulin
  • Peptide Fragments
  • Protein Precursors
  • Sweetening Agents
  • Aspartic Acid
  • Phenylalanine
  • Glucagon-Like Peptide 1
  • Glucagon
  • Cholecystokinin
  • Aspartame