title: Aspartame: review of recent experimental and observational data.
abstract: In this report the neurotoxicity of aspartame and its constituent amino acids aspartic acid and phenylalanine is reviewed. The adverse reactions ascribed to the consumption of aspartame-containing products, as reported in the U.S.A., are discussed and placed in perspective with the results of recent behavioural studies in humans and animals. The issue of common intake levels associated with proposed uses of aspartame is addressed. In brief, the following conclusions can be drawn: When aspartame is consumed at levels within the ADI-limit of 40 mg/kg body wt, there is no significant risk for an aspartate-induced neurotoxic effect in the brain. When aspartame is consumed at levels within the ADI-limit by normal subjects or persons heterozygous for phenylketonuria (PKU) the resultant plasma phenylalanine concentrations are practically always within the normal postprandial range; elevation to plasma concentrations commonly associated with adverse effects has not been observed. Persons suffering from phenylketonuria (PKU-homozygotes) on a phenylalanine-restricted diet should avoid consumption of aspartame. PKU-homozygotes on the (less strict) phenylalanine-liberalized diet should be made aware of the phenylalanine content of aspartame. In the available behavioural studies in humans with acute dosing, no adverse effects were observed. Long-term studies on behaviour and cognitive function in (sensitive) humans are lacking. Analyses of adverse reaction reports made by consumers in the U.S.A. have not yielded a specific constellation of symptoms clearly related to aspartame that would suggest a widespread public health hazard associated with aspartame use. Focussed clinical studies are now being carried out in the U.S.A.; the results should provide additional evidence concerning the interpretation of the reports on adverse reactions ascribed to aspartame. In the regulation of admitted uses for aspartame the possibility of intake levels exceeding the ADI-limit in some groups of consumers should be a point of attention.
authors.affiliation: National Institute of Public Health and Environmental Hygiene, Bilthoven, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Janssen
authors.forename: C A
authors.initials: CA
authors.lastname: van der Heijden
mesh_terms: D000818:Animals; D001218:Aspartame / Q000009:adverse effects* / Q000378:metabolism / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004151:Dipeptides / Q000009:adverse effects*; D006801:Humans; D010649:Phenylalanine / Q000097:blood / Q000378:metabolism*; D010661:Phenylketonurias / Q000378:metabolism
chemical_list: D004151:Dipeptides; D010649:Phenylalanine; D001218:Aspartame