Aspartame (ASP), a widely used artificial sweetener, remains the subject of scientific scrutiny regarding its long-term safety. While regulatory agencies assert safety at established acceptable daily intake (ADI) levels, accumulating preclinical rodent data suggests potential adverse effects under chronic exposure conditions. This systematic review and meta-analysis synthesized evidence from 13 rodent studies investigating neurotoxic and metabolic endpoints. Our quantitative meta-analysis of the oxidative stress domain (k = 8) demonstrated a very large and statistically significant increase in oxidative damage (pooled Hedges' g = +4.44; 95% CI: 2.94 to 5.94), suggesting oxidative stress as a major hypothesized mechanism of aspartame-induced injury. Qualitatively, chronic exposure was associated with neurobehavioural deficits, including spatial learning and memory impairments, alongside metabolic dysfunction such as glucose intolerance and dyslipidaemia. Notably, these effects were observed in several studies utilizing doses equivalent to the human ADI. However, the interpretation of these findings is constrained by high statistical heterogeneity (I2 = 85.4%) and a lack of detailed reporting in primary studies, resulting in uncertain internal validity across several risk-of-bias domains. While these results provide a critical signal regarding the neurotoxic and metabolic potential of aspartame, they underscore the urgent need for improved reporting standards in preclinical toxicology and long-term human epidemiological studies to fully clarify its safety profile.
Choudhary et al. (Mon,) studied this question.