Nutr Rev. 2025 Jul 3:nuaf103. Aspartame and Its Potential Neurocognitive Effects in Humans
Abstract
The safety of aspartame, a widely consumed low-calorie artificial sweetener, for human consumption has recently been heavily debated. Published research has demonstrated that aspartame’s breakdown products-aspartic acid, phenylalanine, and methanol-are associated with potential neurotoxicity and possible carcinogenic and metabolic effects in animal models.
For this scoping review, existing literature on neurocognitive effects of aspartame was gathered and analyzed. A search of 3 literature databases (Embase, Ovid MEDLINE, and Web of Science) yielded 170 peer-reviewed, full-text articles. After consideration of exclusion criteria, 29 articles were selected for inclusion.
After reviewing the findings, indications of aspartame’s potential neurotoxic effects were demonstrated: multiple experimental studies revealed histopathological changes, such as elevated oxidative stress markers and neuronal loss, in various brain regions of animal models after exposure to aspartame.
Additional studies showed memory and learning impairments in animal models, as well as behavioral dysfunction and mood disorders indicative of depression and anxiety in both animal and human models, illustrated by processes such as the downregulation of gamma aminobutyric acid signaling and upregulation of glutamate signaling in the amygdala. Notably, many of these studies investigated aspartame’s impact not only at or above the Food and Drug Administration (FDA)-approved level, but below it as well.
Two studies also indicated that populations with preexisting neurocognitive deficits, such as individuals with parkinsonism or preexisting metabolic conditions such as diabetes may have an increased vulnerability to neurocognitive harm when consuming aspartame.
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Nutr Neurosci. 2024 May;27(5):506-519. Aspartame use and Parkinson’s disease: review of associated effects on neurotransmitters, oxidative stress, and cognition
Abstract
Objective: The purpose of this review was to assess the current evidence regarding the associated physiological and cognitive effects of aspartame (APM) consumption and Parkinson’s Disease (PD).
Methods: A total of 32 studies demonstrating effects of APM on monoamine deficiencies, oxidative stress, and cognitive changes were reviewed.
Results: Multiple studies demonstrated decreased brain dopamine, decreased brain norepinephrine, increased oxidative stress, increased lipid peroxidation, and decreased memory function in rodents after APM use. In addition, PD animal models have been found to be more sensitive to the effects of APM.
Discussion: Overall, studies of APM use over time yielded more consistent results.
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Neurology. 2025 Oct 7;105(7):e214023. Association Between Consumption of Low- and No-Calorie Artificial Sweeteners and Cognitive Decline: An 8-Year Prospective Study
Abstract
Background and objectives: Consumption of low- and no-calorie sweeteners (LNCSs) has been associated with adverse health outcomes. However, little is known about the association between consumption of LNCSs and cognition. The aim of this study was to investigate the association between consumption of LNCSs and cognitive decline.
Methods: We conducted a longitudinal observational study using data from civil servants aged 35+ years at baseline who were enrolled in the Brazilian Longitudinal Study of Adult Health and evaluated across 3 study waves (2008-10, 2012-14, and 2017-19). Participants with incomplete dietary data, extreme caloric intake (<1st percentile or >99th percentile), and incomplete data for cognitive tests and covariates at baseline were excluded. A Food Frequency Questionnaire was used to calculate combined and individual consumption of 7 LNCSs (aspartame, saccharin, acesulfame k, erythritol, xylitol, sorbitol, and tagatose). We estimated z-scores across 6 cognitive tests. The association of LNCSs with cognitive decline was evaluated using linear mixed-effects models.
Results: Among 12,772 participants (mean age 51.9 ± 9.0 years, 54.8% women, 43.2% Black/mixed race), the mean consumption of LNCSs was 92.1 ± 90.1 mg/d. Among participants aged younger than 60 years, consumption of combined LNCSs in the highest tertiles was associated with a faster decline in verbal fluency (second tertile: ? = -0.016, 95% CI -0.040 to -0.008; third tertile: ? = -0.040, 95% CI -0.064 to -0.016) and global cognition (second tertile: ? = -0.008, 95% CI -0.024 to 0.008; third tertile: ? = -0.024, 95% CI -0.040 to -0.008). There was no association between tertiles of LNCSs and cognitive decline in participants aged 60+ years.
Consumption of aspartame, saccharin, acesulfame k, erythritol, sorbitol, and xylitol was associated with a faster decline in global cognition, particularly in memory and verbal fluency domains. Consumption of combined LNCSs in the highest tertiles was associated with a faster decline in verbal fluency and global cognition in participants without diabetes and faster decline in memory and global cognition in participants with diabetes.
Discussion: Consumption of LNCSs was associated with an accelerated rate of cognitive decline during 8 years of follow-up. Our findings suggest the possibility of long-term harm from LNCS consumption, particularly artificial LNCSs and sugar alcohols, on cognitive function.
Robert Rodgers PhD
Founder 2004
Parkinsons Recovery®
https://www.parkinsonsrecovery.com






