Association Between Consumption of Low- and No-Calorie Artificial Sweeteners and Cognitive Decline

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. 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 (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. 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: β = -0.016, 95% CI -0.040 to -0.008; third tertile: β = -0.040, 95% CI -0.064 to -0.016) and global cognition (second tertile: β = -0.008, 95% CI -0.024 to 0.008; third tertile: β = -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. 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. Study limitations include self-reported dietary data, selection bias from attrition, and residual confounding from co-occurring health behaviors.