Sugar Substitutes Not So Sweet for Brain Health

Consuming low- and no-calorie artificial sweeteners may harm cognitive function, results of a longitudinal study of middle-aged and older adults showed.

In adjusted analyses, people who consumed the highest total amounts of these sweeteners had a 62% faster decline in overall thinking and memory skills, equivalent to about 1.6 years of aging, than those consuming the lowest amount.

The link was found in people younger than 60 years but not in older adults and was stronger in people with diabetes.

“For neurologists, the key message is that dietary exposures in midlife may impact long-term brain health, and artificial sweeteners may not be the harmless alternatives to sugar that many assume,” study author Claudia Kimie Suemoto, MD, PhD, with University of São Paulo in São Paulo, Brazil, told Medscape Medical News.

“This is important to keep in mind when counseling patients, especially those at higher risk for dementia or those with diabetes who often rely heavily on these products,” Suemoto said.

The findings were published online on September 3 in Neurology.

Higher Consumption, Faster Decline

The research is the largest and longest prospective study to date investigating the association between artificial sweetener consumption and cognitive decline.

“While previous research had linked sweeteners to conditions such as diabetes, cardiovascular disease, and depression, their long-term impact on cognition had not been systematically explored,” Suemoto said.

The study included 12,772 adults participating in the Brazilian Longitudinal Study of Adult Health Brazilian. As part of the study, they underwent standard cognitive tests every 4 years across three study waves (2008-2010, 2012-2014, and 2017-2019).

A food frequency questionnaire was used to calculate combined and individual consumption of seven low- and no-calorie sweeteners, including the artificial sweeteners aspartame, saccharin, and acesulfame-K; the sugar alcohols erythritol, sorbitol, and xylitol; and tagatose, a natural sweetener.

Participants were divided into three groups based on the total amount of sweeteners consumed. The lowest group consumed an average of 20 mg/d and the highest group consumed an average of 191 mg/d. For aspartame, this amount is equal to one can of diet soda. Sorbitol had the highest consumption, with an average of 64 mg/d.

In the overall sample, after a median follow-up of 8 years, participants in the two highest tertiles of combined low- and no-calorie sweetener consumption had a 35% and 62% higher rate of decline in global cognition, respectively, than peers in the lowest tertile. That corresponds to an excess 1.3 and 1.6 years of cognitive aging.

Verbal fluency also suffered, with participants in the two highest tertiles of combined low- and no-calorie sweetener consumption showing 110% and 173% higher rates of decline in verbal fluency decline, respectively.

Long-Term Consequences for Brain Health

In analyses stratified by age, consumption of low- and no-calorie sweeteners was associated with faster decline in global cognition and verbal fluency in those younger than 60 years but not in older individuals.

The association between higher intake of low- and no-calorie sweeteners was more pronounced in people with diabetes, particularly for memory decline, suggesting a heightened vulnerability in this group, the researchers said.

Similar positive associations with cognitive decline were found in analyses looking at consumption of all of the individual low- and no-calorie sweeteners — except for tagatose, the only natural sweetener.

“Our findings highlight the need to look more critically at what we are using to replace sugar in our diets, and they underscore that dietary choices in midlife can have consequences for brain health decades later,” Suemoto told Medscape Medical News.

“For people who love diet sodas and other sugar-free products (including myself), our findings do not mean that people should panic, but they do suggest it is wise to limit consumption as much as possible, ideally avoiding daily use. Whenever possible, choose natural options to add flavor, like fruit, honey, or spices, and try to shift toward a more balanced diet rich in whole foods,” Suemoto advised.

A limitation of the study was that not all artificial sweeteners were included (such as sucralose). And while a validated food frequency questionnaire was used, the possibility of misreporting bias cannot be ruled out. Also, diet was assessed only at baseline, which may reflect diet changes over time.

‘Compelling’ Data

Writing in a linked editorial, Thomas Monroe Holland, MD, with Rush Institute for Healthy Aging, Rush Medical College, Chicago, said the findings are “compelling” and add to “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.”

Although previous research has linked artificially sweetened beverages to cognitive risk, the use of rigorous and advanced statistical techniques in this study “makes the results more accurate and less biased and strengthen our confidence in the observed cognitive associations,” Holland pointed out.

The finding that associations between these sweeteners and cognitive decline were strongest in younger adults has “profound implications for neurologic counseling. This suggests that midlife dietary exposures, decades before cognitive symptoms emerge, may carry life-long consequences for brain health,” Holland wrote.

The findings may prompt neurologists to reconsider standard dietary recommendations, particularly for patients with diabetes, metabolic syndrome, or cerebrovascular risk factors, he said.

The widespread assumption that low- and no-calorie sweeteners represent a safe sugar substitute may be “misguided, especially given their ubiquity in products marketed as ‘healthier’ alternatives,” Holland added.

“For the medical community, this study poses a fundamental question: In our efforts to prevent stroke and preserve cognition through dietary modification, are we inadvertently recommending substances that may accelerate the very cognitive decline we seek to prevent?” Holland concluded.

Note: This article originally appeared on Medscape.