A long-term follow-up study of Brazilian adults showed that higher intakes of a variety of common low-calorie artificial sweeteners were associated with faster declines in memory and thinking skills over time. This association was particularly evident among people under 60 years old and those with diabetes.
People often think of "replacing white sugar with sugar substitutes" as a simple health choice, but this study published in Neurology, a journal of the American Academy of Neurology, suggests that the story at the brain level may be far more complicated than imagined. The study found that high intake of certain sugar substitutes was associated with faster cognitive decline during follow-up, with people with diabetes being more prominently affected.
It’s important to stress that this study does not prove that artificial sweeteners directly damage the brain, but instead found a statistical association that persisted after controlling for a variety of cognitive-related health factors. The research team pointed out that this means that sugar substitutes cannot simply be regarded as a "free" healthy alternative, but their long-term use should be viewed more cautiously.
The study focused on seven widely used low-calorie sweeteners: aspartame, saccharin, acesulfame K-K, erythritol, xylitol, sorbitol and tagatose. These ingredients are commonly found in a variety of highly processed foods and beverages, including flavored waters, sodas, energy drinks, yogurt, and low-calorie desserts, some of which are also sold as bulk sugar substitutes.
Corresponding author Dr. Claudia Kimie Suemoto of the University of São Paulo in Brazil said that low-calorie or no-calorie sweeteners are often regarded as healthy alternatives to sugar, but the research results suggest that some sweeteners may have negative effects on health in the long term.brainadverse health effects.
In terms of research design, the scientific research team tracked 12,772 adults from all over Brazil for about 8 years. The average age of the participants was 52 years old. At the start of the study, all participants filled out a detailed dietary questionnaire that reviewed their food and drink intake over the previous year, which allowed the researchers to estimate total artificial sweetener intake and divide the population into different intake gradients.
The results showed that the average intake of artificial sweeteners in the lowest intake group was 20 mg/day, and that in the highest intake group was 191 mg/day, which is roughly equivalent to the content in a can of diet soda containing aspartame. In terms of single ingredients, sorbitol had the highest average intake at 64 mg/day.
During the follow-up period, participants underwent multiple rounds of cognitive testing at the beginning, middle, and end of the study on several commonly used measures of brain health and aging, including word-finding speed, working memory capacity, delayed recall, and information processing speed.
After adjusting for age, gender, high blood pressure and other health factors in the statistical analysis, the study found that the group with the highest intake of artificial sweeteners declined 62% faster in overall thinking and memory ability than the group with the lowest intake, which is equivalent to an additional 1.6 years of "brain age" aging. The moderate intake group also showed significant differences, with cognitive decline occurring 35% faster than the lowest intake group, roughly equivalent to about 1.3 years of additional aging.
After further analysis stratified by age, the association was more prominent among those under 60 years of age. Among this subset of subjects, the highest intake group experienced significantly faster declines in verbal fluency and overall cognitive performance than the lowest intake group, while no significant association was observed among those over 60 years of age.
Diabetic status also amplified the relationship: Among participants with diabetes, the link between artificial sweetener consumption and cognitive decline was stronger than among those without diabetes. The researchers noted that patients with diabetes are often more likely to use sugar substitutes as a means of controlling their sugar levels, which may make this group of particular concern.
Looking at specific sweeteners, higher intakes of aspartame, saccharin, acesulfame potassium-K, erythritol, sorbitol, and xylitol were all associated with faster degradation of overall cognitive function, especially memory. Of the seven ingredients analyzed, tagatose was the only sweetener not shown to be associated with cognitive decline.
Suemoto said the study not only found a correlation among middle-aged diabetics but also observed similar trends among middle-aged people without diabetes, but given that diabetics more frequently choose artificial sweeteners, how to provide them with safer alternatives is particularly important. She also called for more research to validate existing findings and explore whether other refined sugar alternatives such as applesauce, honey, maple syrup, coconut sugar, etc., might be more suitable options.
The research team also admitted that this study has limitations: first, it does not cover all types of artificial sweeteners on the market; second, dietary data relies on self-reporting, and subjects' recall of their diet in the past year is inevitably biased. Therefore, no conclusive causal judgment can be made based on this at this stage, but it should be regarded as an important risk signal and a starting point for future research.
This work was funded by the Brazilian Ministry of Health, the Ministry of Science, Technology and Innovation, the National Council for Scientific Research and Development and other institutions. The main article and supporting review articles were published in the magazine "Neurology" on September 3, 2025. The research has sparked a new round of discussion about whether sugar-free sweeteners are as safe as advertised, and has also given the public and clinicians more considerations when weighing sugar control, weight management and long-term brain health.