Sugar substitutes have long been promoted as a healthier way to enjoy sweet foods and drinks without consuming the high calories and metabolic drawbacks of traditional sugar. From morning diet sodas to low-calorie yogurts and sugar-free snacks, millions of consumers worldwide rely on these alternatives to help manage their weight and blood sugar levels. However, new research suggests that some of these widely used sweeteners may carry an unexpected and concerning downside for long-term brain health, prompting new questions about their safety and everyday use.
A comprehensive study published in Neurology, the medical journal of the American Academy of Neurology, has found that people who consumed the highest amounts of low- and no-calorie sweeteners experienced significantly faster declines in memory and thinking skills compared to those who consumed the least. Most notably, this association was particularly pronounced among individuals living with diabetes, a population that frequently turns to sugar substitutes as a dietary safeguard.
The research team focused its investigation on seven distinct sweeteners that are commonly found in everyday foods and beverages. These ingredients include aspartame, saccharin, acesulfame-K, erythritol, xylitol, sorbitol, and tagatose. These compounds frequently appear in a vast array of ultra-processed products, ranging from diet sodas and flavored sparkling waters to energy drinks, flavored yogurts, and low-calorie desserts. Additionally, many of these substances are sold individually as tabletop sweeteners for home use in coffee, tea, and cooking.
"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 lead study author Dr. Claudia Kimie Suemoto, MD, PhD, an associate professor at the University of São Paulo in Brazil.
Despite the concerning trends observed in the data, researchers emphasize that the findings demonstrate an association rather than a proven cause-and-effect relationship. Consequently, scientists cannot conclude from this observational study alone that consuming these artificial or low-calorie sweeteners directly damages the structural integrity of the brain or triggers permanent memory loss. Nonetheless, the strength of the statistical link warrants a closer look at how these chemical alternatives interact with human metabolism and neurological function over extended periods.
Study Tracks Nearly 13,000 Adults for Eight Years
To investigate whether sugar substitutes might be connected to long-term cognitive health, researchers analyzed longitudinal data gathered from 12,772 adult participants across Brazil. The cohort was diverse, with participants averaging 52 years of age at the start of the research project, and they were followed closely for an average duration of approximately eight years.
At the very beginning of the study, participants completed detailed dietary questionnaires designed to capture their eating and drinking habits over the preceding year. Researchers used these comprehensive responses to estimate each individual’s daily intake of the seven targeted sweeteners, establishing a baseline to measure subsequent changes in mental acuity.
Participants were subsequently divided into three distinct groups based on the volume of sweeteners they consumed. Those in the lowest consumption tier averaged a meager 20 milligrams per day, while individuals in the highest consumption group ingested an average of 191 milligrams per day. To put these figures into a practical perspective, 191 milligrams of aspartame is roughly equivalent to the amount found in a single standard can of diet soda.
Among the seven individual sweeteners examined in the study, sorbitol registered the highest average daily intake among participants, recording an average of 64 milligrams per day. Sorbitol belongs to a chemical classification known as sugar alcohols, or polyols, which mimic the sweetness of sucrose while providing fewer calories and are widely utilized in commercial food manufacturing as sugar substitutes.
Throughout the multi-year study, participants underwent rigorous cognitive assessments at three critical junctures: the beginning, the middle, and the end of the tracking period. These standardized tests were designed to measure several vital cognitive faculties essential for everyday mental functioning, including memory retention, linguistic ability, and the speed at which the human brain processes complex information.
Specifically, researchers evaluated verbal fluency—the psychological capacity to quickly retrieve and produce words upon demand—alongside working memory, which allows individuals to temporarily hold, manipulate, and utilize information in real-time. They also tested word recall capabilities and overall processing speed to meticulously track how these vital mental faculties shifted and evolved over the multi-year study period.
High Sweetener Consumption Linked to 62% Faster Cognitive Decline
The final results revealed a striking and statistically significant difference in cognitive trajectories between the individuals who consumed the highest levels of sweeteners and those who consumed the least.
After adjusting and accounting for a wide array of potential confounding factors that could naturally influence cognitive health—including age, biological sex, high blood pressure, and existing cardiovascular disease—the researchers uncovered a troubling pattern. Participants who fell into the highest consumption group experienced a 62% faster decline in their overall thinking and memory abilities compared to those in the lowest consumption tier.
To help contextualize these figures, the researchers noted that this rate of decline was roughly equivalent to experiencing approximately 1.6 additional years of natural cognitive aging over the course of the study period.
Even moderate consumption levels were associated with measurable differences in mental performance. Participants placed in the middle consumption group experienced a 35% faster cognitive decline than those consuming the lowest amounts, a deficit roughly equivalent to experiencing about 1.3 additional years of cognitive aging.
The study authors pointed out that these estimates describe statistical changes in cognitive test performance over time rather than a direct, biological measurement of physical brain aging. Furthermore, these statistical associations do not imply that every individual who consumes artificial or low-calorie sweeteners will inevitably suffer from clinical memory problems or cognitive impairment.
Stronger Links Found in Adults Under 60 and People With Diabetes
When the researchers disaggregated the data to examine different demographic cohorts, they discovered that the association between sweeteners and cognitive decline was not uniformly distributed across all participants.
Among adults younger than 60 years old, higher sweetener consumption was linked to notably faster declines in verbal fluency and overall cognitive performance. Intriguingly, researchers did not find a similar, statistically significant association among participants who were older than 60 at the start of the study, suggesting that middle-aged adults may be particularly vulnerable to the metabolic or neurological impacts of these substances.
Furthermore, the relationship between sweetener intake and cognitive decline was markedly stronger in individuals diagnosed with diabetes compared to those without the metabolic condition. This particular discovery carries immense public health relevance, given that people with diabetes frequently and heavily rely on sugar substitutes as a primary strategy to manage their blood sugar levels and avoid the glycemic spikes associated with real sugar.
When the team examined the seven specific sweeteners individually, nearly all of them shared similar statistical profiles. Six of the seven substances—specifically aspartame, saccharin, acesulfame-K, erythritol, sorbitol, and xylitol—were individually associated with faster rates of decline in overall cognitive performance, with a pronounced impact on memory.
Tagatose stood out as the sole exception to this trend. The researchers found no discernible statistical association between the consumption of tagatose and cognitive decline within this study group. However, the study authors were careful to clarify that this finding does not establish tagatose as a brain-protecting agent, nor does it prove that it is inherently safer than its industry counterparts.
Should People Rethink Artificial Sweeteners?
The unsettling findings raise pressing questions regarding whether substituting refined sugar with low-calorie and artificial alternatives consistently delivers the health benefits that consumers expect, particularly when it comes to the long-term vitality of the human 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," Dr. Suemoto noted. She added that considerably more scientific research is urgently needed to confirm these preliminary findings and to investigate whether other unrefined or alternative sweeteners—such as applesauce, honey, maple syrup, or coconut sugar—might serve as safer or more effective alternatives for daily consumption.
The researchers were also transparent about several inherent limitations in their study design. For instance, the analytical scope did not encompass every single artificial or low-calorie sweetener currently available on the commercial market, meaning the conclusions cannot be broadly applied to every sugar substitute in existence.
Additionally, the dietary data relied heavily on participants’ retrospective recollections of what they had eaten and drunk over the previous year. Because human memory is fallible, and individuals frequently forget certain foods, underestimate portion sizes, or inaccurately report their dietary habits, these self-reported estimates may not perfectly mirror actual lifetime sweetener consumption.
The observational nature of the research also means that residual confounding factors—variables that were not fully captured or controlled for—could theoretically help explain the observed relationship between heavy sweetener intake and cognitive decline, despite the researchers’ thorough statistical adjustments for established health variables.
Consequently, further clinical and epidemiological studies will be required to definitively determine whether the sweeteners themselves actively contribute to pathological changes in brain function, why certain demographic groups appear considerably more vulnerable to these effects, and whether different classes of sugar alternatives yield divergent long-term health outcomes.
The underlying research project received financial backing and support from the Brazilian Ministry of Health, the Ministry of Science, Technology, and Innovation, and the National Council for Scientific and Technological Development.