The Neuropsychiatric Effects of Aspartame in Normal Volunteers

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Abstract
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 postdosage: 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 < .01) than with placebo between 1 and 6 hours postdosage, reaching a maximum difference of +3.36 μmol/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.