Six popular sugar substitutes linked to faster brain aging

Sugar substitutes are often promoted as a healthier way to enjoy sweet foods and drinks without consuming as much sugar. However, new research suggests that some of these widely used sweeteners may have an unexpected downside for long-term brain health.

A study published in Neurology, the medical journal of the American Academy of Neurology, found that people who consumed the most low- and no-calorie sweeteners experienced significantly faster declines in memory and thinking skills than those who consumed the least. The association was particularly pronounced among people with diabetes.

Researchers examined seven sweeteners commonly used in foods and beverages: aspartame, saccharin, acesulfame-K, erythritol, xylitol, sorbitol and tagatose. These ingredients frequently appear in ultra-processed products, including diet sodas, flavored waters, energy drinks, yogurt and low-calorie desserts. Some are also sold separately for sweetening foods and beverages.

"Low- and no-calorie sweeteners are often seen as a healthy alternative to sugar; however, our findings suggest certain sweeteners may have negative effects on brain health over time," said study author Claudia Kimie Suemoto, MD, PhD, of the University of São Paulo in Brazil.

Importantly, the findings show an association rather than a proven cause-and-effect relationship. Researchers cannot conclude from this study that consuming these sweeteners directly damages the brain or causes memory loss.

To investigate whether sugar substitutes might be connected to cognitive health, researchers analyzed data from 12,772 adults across Brazil. Participants were 52 years old on average when the study began and were followed for approximately eight years.

At the beginning of the study, participants completed detailed dietary questionnaires describing the foods and drinks they had consumed during the previous year. Researchers used these responses to estimate each person's daily intake of the seven sweeteners.

Participants were then separated into three groups according to how much of the sweeteners they consumed. Those in the lowest consumption group averaged 20 milligrams per day (mg/day), while those in the highest group averaged 191 mg/day. For comparison, 191 milligrams of aspartame is roughly the amount found in one can of diet soda.

Of the seven sweeteners examined, sorbitol had the highest average intake, at 64 mg/day. Sorbitol belongs to a category of sweeteners called sugar alcohols, which provide sweetness and are commonly used as sugar substitutes.

Throughout the study, participants completed cognitive assessments at three points: the beginning, middle, and end. These tests measured several abilities essential for everyday mental functioning, including memory, language, and the speed at which the brain processes information.

Researchers evaluated verbal fluency, or the ability to quickly retrieve and produce words, along with working memory, which allows people to temporarily hold and use information. They also tested word recall and processing speed to determine how these abilities changed over time.

The results revealed a striking difference between people who consumed the most sweeteners and those who consumed the least.

After accounting for factors that could influence cognitive health, including age, sex, high blood pressure, and cardiovascular disease, researchers found that participants in the highest consumption group experienced a 62% faster decline in overall thinking and memory abilities compared with those in the lowest group.

Even moderate consumption was associated with measurable differences. Participants in the middle group experienced a 35% faster decline than those consuming the least, equivalent to roughly 1.3 additional years of cognitive aging.

These estimates describe changes in cognitive test performance rather than a direct measurement of biological brain aging. They also do not mean that everyone who consumes artificial sweeteners will experience memory problems.

When researchers examined different age groups, they discovered that the association was not consistent across all participants.

Among adults younger than 60, higher sweetener consumption was linked to faster declines in verbal fluency and overall cognitive performance. However, researchers did not find a similar association among participants older than 60.

The relationship was also stronger in people with diabetes than in those without the condition. This finding is especially relevant because people with diabetes frequently turn to sugar substitutes to help manage their sugar intake.

Those six were aspartame, saccharin, acesulfame-K, erythritol, sorbitol and xylitol.

Tagatose was the exception. Researchers found no association between its consumption and cognitive decline in this study. However, that finding does not establish that tagatose protects the brain or is necessarily safer than other sweeteners.

The findings raise important questions about whether replacing sugar with low-calorie alternatives always delivers the health benefits consumers expect, particularly when it comes to the brain.

"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. "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."

Researchers also acknowledged several limitations. The analysis did not cover every artificial sweetener available on the market, so the findings cannot necessarily be applied to all sugar substitutes.

In addition, dietary information came from participants' own recollections of what they had eaten and drunk. Because people may forget foods, underestimate portions, or inaccurately report their habits, these estimates may not perfectly reflect actual sweetener consumption.

The observational design also means that other factors could help explain the relationship between sweetener intake and cognitive decline, despite researchers' efforts to account for several important health differences.

Further studies will be needed to determine whether the sweeteners themselves contribute to changes in brain function, why certain groups appear more strongly affected, and whether different sugar alternatives produce different long-term outcomes.

The research was supported by the Brazilian Ministry of Health, the Ministry of Science, Technology, and Innovation, and the National Council for Scientific and Technological Development.