Aspartame-induced cognitive dysfunction: Unveiling role of microglia-mediated neuroinflammation and molecular remediation

Aspartame, an artificial sweetener, is consumed by millions of people globally. There are multiple reports of aspartame and its metabolites affecting cognitive functions in animal models and humans, which include learning problems, headaches, seizures, migraines, irritable moods, anxiety, depression, and insomnia. These cognitive deficits and associated symptoms are partly attributed to dysregulated excitatory and inhibitory neurotransmitter balance due to aspartate released from aspartame, resulting in an excitotoxic effect in neurons, leading to neuronal damage. However, microglia, a central immunocompetent cell type in brain tissue and a significant player in inflammation can contribute to the impact. Microglia rapidly respond to changes in CNS homeostasis. Aspartame consumption might affect the microglia phenotype directly via methanol-induced toxic effects and indirectly via aspartic acid-mediated excitotoxicity, exacerbating symptoms of cognitive decline. Long-term oral consumption of aspartame thus might change microglia's phenotype from ramified to activated, resulting in chronic or sustained activation, releasing excess pro-inflammatory molecules. This pro-inflammatory surge might lead to the degeneration of healthy neurons and other glial cells, impairing cognition. This review will deliberate on possible links and research gaps that need to be explored concerning aspartame consumption, ecotoxicity and microglia-mediated inflammatory cognitive impairment. The study covers a comprehensive analysis of the impact of aspartame consumption on cognitive function, considering both direct and indirect effects, including the involvement of microglia-mediated neuroinflammation. We also propose a novel intervention strategy involving tryptophan supplementation to mitigate cognitive decline symptoms in individuals with prolonged aspartame consumption, providing a potential solution to address the adverse effects of aspartame on cognitive function.