Introduction: Aspartame, a widely consumed artificial sweetener, raises concerns regarding its potential neurotoxic effects mediated through oxidative stress pathways. This systematic review and meta-analysis quantified the relationship between aspartame exposure and oxidative stress biomarkers that affect learning and memory. Methods: A comprehensive systematic review was conducted following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were performed across multiple databases, including PubMed, MEDLINE, and Google Scholar, for studies published between 2015 and 2025. The review included studies that investigated the effects of aspartame exposure on learning and memory, as well as oxidative stress measurements. A random-effects meta-analysis was performed using the DerSimonian-Laird method, with effect sizes calculated as Cohen’s d. This was followed by a dose-response meta-regression analysis. The risk of bias was rigorously assessed using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) criteria. Results: From an initial pool of 264 records, 10 studies met the predefined inclusion criteria. Meta-analysis revealed significant increases in reactive oxygen species (ROS) (pooled effect size: 2.140, 95% CI: 1.514-2.767) and malondialdehyde (MDA) (1.773, 95% CI: 1.230-2.317). Concurrently, significant decreases were observed in glutathione (GSH) (-1.809, 95% CI: -2.339 to -1.279) and superoxide dismutase (SOD) (-1.438, 95% CI: -1.915 to -0.962). All observed effects were highly significant (p 0.92) across all biomarkers and predicted large oxidative effects (Cohen’s d > 1.2) across all evaluated biomarkers. Discussion: This study evidence that aspartame exposure results in oxidative stress in a dosedependent fashion. ROS has been established as the most sensitive bio-signature of the early occurrence of these effects in the body. These data indicate that aspartame may be an important environmental factor for the development of oxidative stress in the brain, and current safety standards may not be sufficient to avoid biochemical effects, based on our experimental conditions. Conclusion: This is a very clear aspartame dose-dependent relationship in describing a toxic effect of aspartame. The results underscore the urgent necessity of re-evaluating the established daily intake of aspartame for humans to a more realistic, decreased value in order to approach or reach only theoretical risk levels.
Choudhary et al. (Mon,) studied this question.