Title : Aspartame and its potential neurocognitive effects in humans: A scoping review
Abstract:
Background: The safety of aspartame, a widely consumed low-calorie artificial sweetener, has been heavily debated for human consumption. Published research has demonstrated its breakdown products, aspartic acid and phenylalanine, are associated with potential neurotoxicity due to their ability to activate glutamate receptors and a correlation between aspartame consumption and carcinogenic and metabolic effects in animal models. Neurocognitive implications must be further assessed for consumer safety.
Objective: To evaluate the extent of literature on the neurocognitive effects of aspartame.
Methods: Following PRISMA-ScR, we searched peer-reviewed literature using databases EMBASE, OViD MEDLINE, and Web of Science. Search strategy was limited to full-text studies published in English between 2013 and 2023, excluding review articles. Using the search terms “aspartame”:exp, Aspartame AND neuro*, (aspartame) AND (neuro* OR memory OR dementia), Aspartame AND health*, aspartame AND health AND human*, the initial search yielded 170 articles. After filtering based on inclusion and exclusion criteria and quality of the design and results, 29 articles were selected.
Results: The domains for data extraction were 1) dose-independent and dose-dependent changes in brain and neuronal cells, 2) memory/cognition, 3) behavior/mood and 4) potential neuroprotective agents. Multiple experimental studies involving rats exposed to aspartame over a period of several weeks revealed histopathological changes in the brain such as neuronal damage, reactive gliosis, and increases in oxidative stress markers in the hippocampus, cerebral cortex, and striatal tissue samples, indicating that aspartame has potential neurotoxic effects. Others showed memory and learning impairments in rodents after aspartame ingestion, as well as an association with mood disorders such as depression and anxiety in both human and rodent models. One study showed the consumption of aspartame increased anxiety levels in rodents by down-regulating GABA signaling and up-regulating glutamate signaling in the amygdala. Similarly, adults who frequently consumed beverages containing aspartame were found to exhibit increased levels of depression. Interestingly, mice with induced Parkinsonism consuming aspartame demonstrated a significant decrease in dopamine concentration as well as cognitive changes, such as immobility suggestive of behavior resembling depression and impaired memory. Lastly, diabetic rats consuming aspartame were found to be more aggressive and anxious than their nondiabetic counterparts and had indications of cognitive dysfunction by impaired memory and learning behaviors. Nonetheless, multiple experiments demonstrated potential ameliorative compounds, such as β-caryophyllene, Pimpinella anisum oil, vitamin E, L-carnitine, and a combination of N-acetyl-L-cysteine and folic acid, that may have neuroprotective benefits with aspartame administration.
Conclusions: This review highlighted the negative neurocognitive effects of aspartame consumption, such as neuronal damage, deficits in spatial learning and memory retention, as well as behavioral and mood alterations in both rodent and human subjects and further emphasized its detrimental effects on populations diagnosed with certain conditions such as Parkinson’s disease or diabetes. Aspartame’s common use as a “healthier” sugar replacement needs to be reevaluated and caution needs to be taken in the advisement of its use in clinical practice. Further research involving human subjects in controlled settings is required to reassess aspartame’s safety and enable informed decision-making among consumers.
Audience Take Away Notes:
- Provides background for future research on aspartame consumption and neurocognitive changes in human subjects
- Recall indications to exercise caution with aspartame consumption in people diagnosed with Parkinson’s disease or diabetes
- Recognize molecular effects of aspartame on the brain and its implications on memory, cognition, behavior, and mood
- Identify new research applications for compounds with the potential to offset the negative neurocognitive impacts of aspartame
