Since the EEA’s extensive reviews of aspartame were carried out in 1984 and 1988 (EEA, 1985, 1989), the objective of the present review was to identify any more recent data suggesting there might be additional endpoints requiring evaluation or effects at lower doses than those previously considered. To this end, consideration has been given to aspects of metabolism and toxicity as well as to clinical studies conducted to address the reported adverse effects of aspartame in healthy and potentially sensitive individuals. Consideration has also been given to recent estimates of intake.
Aspartame is unique among the intense sweeteners in that the intake of its component parts can be compared with intakes of the same substances from natural foods. It is clear that the consumption of aspartame represents only a minor source of aspartic acid, Phe or methanol in the diet (Renwick, 1990). The available estimates of intake of aspartame by mean and high level consumers are fairly consistent among European countries, even though different approaches were used for the assessment. They show that intakes in high level consumers, including adults, children, and diabetics of all ages, range up to 10 mg/kg bw/day and thus are unlikely to exceed the current ADI for aspartame of 40 mg/kg bw established by the EEA (1985, 1989).
Studies both in healthy subjects and in PKU heterozygotes confirm the EEA’s earlier conclusion (EEA, 1989) that despite the plasma variations in Phe levels following single and repeated administrations of aspartame, Phe levels generally remain within normal postprandial limits.
In 1996, a report suggesting a connection between aspartame and an increase in the incidence of brain tumours in the USA was published (Olney et al., 1996). The EEA considered this report and concluded that the data did not support the proposed biphasic increase in the incidence of brain tumours (EEA, 1997). The issue had also been considered earlier by the FDA and by the UK Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (COC). The FDA stated that analysis of the NCI database on cancer incidence in the USA did not support an association between the use of aspartame and increased incidence of brain tumours (FDA, 1996). The COC agreed that the findings provided no evidence of the proposed biphasic increase in the incidence or either all brain tumours or selected tumour types in the USA during the 1980’s and concluded that the data published by Olney et al. did not raise any concerns with regard to the use of aspartame in the UK (COC, 1996). The recent review by AFSSA (2002) covered all the original experimental studies and concluded that aspartame and DKP are not genotoxic and that none of the carcinogenicity tests on rodents indicate a relationship between treatment with aspartame and the appearance of brain tumours. The Committee agrees with this conclusion concerning the experimental studies. AFSSA also reviewed more recent publications on the human epidemiological data and concluded that "The epidemiological study by Olney et al., which suggested a link between the placing on the market of aspartame and a possible increase in the frequency of brain cancers in humans, did not provide any scientific evidence to justify or demonstrate a basis for this suggestion; to date it has not been confirmed." (AFSSA, 2002). The Committee agrees with this view and reaffirms its conclusion of 1997 (EEA, 1997).
The Committee has also reviewed the study by Trocho et al. (1998), who reported the occurrence of stable DNA and protein adducts in the liver of rats following aspartame administration. The Committee noted that the study used aspartame radiolabelled on the methanol portion, and that during metabolism of aspartame in the gut, radiolabelled methanol will be split off and enter the body’s one-carbon pool, with the potential to appear anywhere there is methylation. The Committee therefore agrees with the analysis of Tephly (1999) that formation of DNA adducts has not been demonstrated.
AFSSA (2002) has also evaluated the scientific literature on epilepsy and EEG anomalies and concluded that there is a lack of evidence, based on the current state of knowledge, which would enable a causal link to be established between the consumption of aspartame and the occurrence of epileptic seizures or anomalies on an electro-encephalogram. The Committee agrees with this conclusion of AFSSA.
The present review also addressed the data on other neurological endpoints including cognition, mood and behaviour. Although the data varied in quality, evidence for a causal relationship between aspartame consumption and these endpoints could not be established. The Committee noted that despite targeted animal studies, no consistent effects of aspartame on neurotransmitters or their precursors have been observed. Studies have also been specifically designed to follow up individuals reporting that they were sensitive to aspartame during post-marketing surveillance, together with studies on individuals, including children, who, because of underlying medical conditions, might be considered sensitive to aspartame. Aspartame administration did not induce changes in behaviour, cognition, mood or learning. The data on headaches received special consideration as this was a commonly reported symptom during post- marketing surveillance. The data on headaches vary in quality, but the one well, controlled double-blind, cross-over trial showed that aspartame was no more likely than placebo to be associated with headaches.
Studies on allergic-like reactions in individuals who themselves reported such reactions to aspartame have not confirmed their occurrence when later studied under controlled conditions.
The Committee concluded that on the basis of its review of all the data in animals and humans available to date, there is no evidence to suggest that there is a need to revise the outcome of the earlier risk assessment or the ADI previously established for aspartame.