The neuropsychiatric effects of aspartame in normal volunteers

J Clin Pharmacol. 1990 May;30(5):454-60. doi: 10.1002/j.1552-4604.1990.tb03485.x.


Ten healthy volunteers with no history of aspartame intolerance (6 men and 4 women, aged 21-36 years) received a single dose of aspartame (15 mg/kg body weight in capsules) or matching placebo in a randomized, double-blind crossover study. Eleven blood samples collected over 24 hours were analyzed for plasma glucose and amino acid concentrations. The following variables were evaluated at 1, 2, 4, 8, and 24 hours post-dosage: changes in mood measured on visual analog scales, cognitive function determined by digit-symbol substitution test (DSST) and arithmetic test scores, and reaction time measured with a brake-pedal reaction timer. Memory was tested at 2 and 24 hours after dosage based on recall of standardized 16-item word lists. No significant differences between aspartame and placebo were found in measures of sedation, hunger, headache, reaction-time, cognition, or memory at any time during the study. Plasma phenylalanine levels were significantly higher following aspartame (P less than .01) than with placebo between 1 and 6 hours postdosage, reaching a maximum difference of +3.36 mumols/dl at 2 hours. Plasma glucose concentrations were not significantly different between aspartame and placebo. The results of this study suggest that following a single 15 mg/kg dose of aspartame, no detectable effects are observed in a group of healthy volunteers with no history of aspartame intolerance, despite significant increases in plasma phenylalanine concentrations.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Affect / drug effects*
  • Amino Acids / blood
  • Aspartame / administration & dosage
  • Aspartame / adverse effects
  • Aspartame / pharmacology*
  • Blood Glucose / analysis
  • Cognition / drug effects*
  • Dipeptides / pharmacology*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Memory / drug effects
  • Phenylalanine / blood
  • Product Surveillance, Postmarketing
  • Random Allocation
  • Reaction Time / drug effects*
  • Time Factors


  • Amino Acids
  • Blood Glucose
  • Dipeptides
  • Phenylalanine
  • Aspartame