Midlife Brain Power Drops As Artificial Sweetener Use Rises

By Judy George

Higher artificial sweetener intake was linked with faster cognitive decline in middle-age adults.

No association emerged between sweetener use and decline in people ages 60 and older.

Cognitive decline was tied to artificial sweeteners in people with and without diabetes.

Midlife cognitive scores fell as intake of low-calorie and no-calorie artificial sweeteners rose, a longitudinal study of civil servants in Brazil showed.

People ages 35 to 59 in the highest tertiles of artificial sweetener use had faster declines in verbal fluency (second tertile: β = -0.016; third tertile: β = -0.040) over 8 years, reported Claudia Kimie Suemoto, MD, PhD, of the University of São Paulo, and co-authors.

Compared with those in the lowest tertile, they also had faster downturns in global cognition (second tertile: β = -0.008; third tertile: β = -0.024), the researchers wrote.

There was no association between low- and no-calorie sweeteners and cognitive changes in people ages 60 or older.

Consumption of aspartame, saccharin, acesulfame-k, erythritol, sorbitol, and xylitol was tied to faster drops in global cognition, particularly in memory and verbal fluency domains. No link between tagatose, a natural sugar, and cognitive decline emerged.

In people without diabetes, the highest level of artificial sweetener use was associated with faster declines in verbal fluency and global cognition. In people with diabetes, the highest use was linked with faster downturns in memory and global cognition.

"While we found links to cognitive decline for middle-aged people both with and without diabetes, people with diabetes are more likely to use artificial sweeteners as sugar substitutes," Suemoto said in a statement. "More research is needed to confirm our findings and to investigate if other refined sugar alternatives, such as applesauce, honey, maple syrup, or coconut sugar, may be effective alternatives."

Sugar-free ultraprocessed foods -- diet beverages, energy drinks, yogurts, snacks, low-calorie desserts, and milk-based beverages, for example -- often contain low- and no-calorie sweeteners, the researchers noted. Some studies have found that late-life consumption of sugar-sweetened or artificially sweetened beverages was not associated with dementia. Others have linked sweetened beverages with stroke and cognitive risk.

The current study "builds on mounting evidence that common dietary exposures, particularly ultraprocessed food additives, once considered benign, may influence brain health in ways neurologists and other healthcare professionals are only beginning to understand," observed Thomas Holland, MD, MS, of Rush Medical College in Chicago, in an accompanying editorial.

This research has several key implications for clinicians, Holland noted. Its use of rigorous statistical modeling "strengthen our confidence in the observed cognitive associations," he wrote. In addition, assessments of individual sweeteners suggest that "multiple low- and no-calorie sweeteners, not just erythritol, may pose cognitive risks."

The biological mechanisms underlying these findings may hold particular relevance for neurologists, he said. "Erythritol has been linked to increased platelet reactivity, thrombosis potential, and impaired endothelial nitric oxide production," Holland pointed out.

"These vascular effects raise serious concerns for brain health given that cerebrovascular disease underlies many dementias and nitric oxide plays a critical role in maintaining cerebral perfusion," he added. "In addition, elevated oxidative stress and neuroinflammation, possibly triggered by low- and no-calorie sweetener metabolites, represent proposed mechanisms that align with known pathways of cognitive impairment."

Suemoto and colleagues studied 12,772 civil servants ages 35 and up enrolled in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), following them for a median of 8 years. Cognitive performance was assessed every 4 years.

Mean baseline age was 52. About half (54.8%) of the study group were women, and 43.2% were Black or mixed race. Food frequency questionnaires were used to calculate combined and individual intake of seven low- and no-calorie sweeteners.

Participants were grouped into tertiles based on their low- and no-calorie sweetener consumption. The lowest tertile consumed an average of 19.9 mg/day; the highest group consumed an average of 191.0 mg/day. Sorbitol had the highest consumption, with an average of 63.8 mg/day.

The study relied on food frequency questionnaires, and the possibility of misreporting bias cannot be ruled out, the researchers acknowledged. Food consumption was measured only once, at baseline. Some sweeteners, like sucralose, were not included.

Many covariates in this analysis were self-reported, Suemoto and co-authors added. While regression models were adjusted for several clinical and lifestyle variables, residual confounding may have occurred.