People domesticated sugarcane around 8,000 years ago in Papua New Guinea, and by about 5000 years later, Indian producers had developed methods to extract solid sugar.
Sugar, transformed from a rare luxury into a ubiquitous commodity during the 16th–18th centuries, became central to European and American markets as large-scale production on colonial plantations became the norm—an expansion relying heavily on enslaved labor. The unprecedented availability drove correspondingly high consumption.
According to research published in Nutrients, using data from the 2015–2016 NHANES, Americans consume approximately 17 teaspoons (68 grams) of added sugar per day, exceeding the WHO recommendation by about one-third. Given the well-established link between excessive sugar intake, obesity, and other diet-related chronic illnesses, many individuals have adopted non-caloric sweeteners (NCS) as a dietary substitute.
International regulatory agencies classify NCS as safe when consumed within established Acceptable Daily Intake (ADI) limits. However, over the past decade, researchers have questioned the long-term effects of NCS on gut microbiota, metabolic regulation, and cardiovascular health. Observational studies have reported associations with elevated insulin, dysbiosis, paradoxical weight gain, and cardiovascular issues. Crucially, these findings reflect correlations rather than causation, emphasizing the need for careful interpretation.
The most recent public concern arose from a study published in Neurology, which reported an association between non-caloric sweetener consumption and cognitive decline in a large cohort of Brazilian adults. International media coverage was predictably sensationalized, with headlines such as “Sweeteners can harm cognitive health equivalent to 1.6 years of aging, study finds.” Beneath the sensationalism, however, the study represents a methodologically robust effort worthy of careful examination.
The Elsa Study
ELSA-Brasil is a cohort study of 15,105 civil servants aged 35–74 years from six institutions across Brazil. Researchers follow participants over time to examine how exposures (e.g., diet, pollutants, and activities) relate to outcomes (e.g., health conditions). This study has produced numerous publications, including the Neurology article, which investigates the incidence and progression of diabetes and cardiovascular diseases.
At baseline, participants completed a variety of tests and interviews, including cognitive testing. One assessing memory (word learning and retention) and two evaluating executive functions (attention, concentration, and psychomotor speed). Researchers repeated these tests at follow-up to track changes in cognitive performance. Researchers assessed dietary intake using a semi-quantitative, 114-item Food Frequency Questionnaire (FFQ). The FFQ included items on sweetened beverages (“with sugar,” “with sweetener,” and “without sugar”), as well as on eating habits such as fast-food and sweet-food consumption.
The final sample included 9,226 individuals. Researchers defined regular NNS consumption as the daily intake of at least one NNS-sweetened product. Overall, 25.7% of participants reported regular use, primarily in their coffee (20.9%). In adjusted models, higher education and income increased the likelihood of regular NNS use by approximately 80%, while moderate-to-vigorous leisure-time physical activity increased it by about 30%.
This analysis provides the basis for the Neurology study. However, despite their best efforts, several limitations remain: observational studies preclude causal inference, dietary assessment tools are prone to bias, and despite statistical “adjustment,” residual confounding may persist.
Do Sweeteners Accelerate Cognitive Decline?
Published in Neurology, the study investigated whether consumption of seven low- or no-calorie sweeteners (LNCS) is associated with cognitive decline over eight years, hypothesizing that higher intake accelerates decline.
. Participants were classified by frequency of LNCS use into two groups: less than once per day and “daily consumption”, and consumption amounts were categorized into three increasing amounts (tertiles). The study included three waves of cognitive performance, every 4 years, for a baseline of 12,772 individuals.
Analyses were adjusted for sociodemographic and lifestyle factors, metabolic variables, and diet quality, measured using the MIND dietary pattern, which emphasizes leafy green vegetables, red fruits, and olive oil while discouraging fried foods, sweets, and red meat.
After eight years, participants in the highest LNCS consumption tertile showed faster cognitive decline than those in the lowest tertile:
- Memory declined 32% faster
- Verbal fluency declined 110% in the second tertile and 173% in the third (highest) tertile
- Global cognition declined 35% and 62% faster, corresponding to approximately 1.3–1.6 years of “excess cognitive aging.”
- Among participants <60, the highest LNCS intake was associated with a faster decline in verbal fluency and global cognition; no associations were observed among those ≥60.
- Saccharin and xylitol affected memory and global cognition, while tagatose affected executive function in individuals with diabetes. In non-diabetic participants, higher LNCS intake was associated with faster decline in verbal fluency and global cognition
- Aspartame was associated with the fastest decline across all domains, while acesulfame-K and erythritol were related to declines in memory and global cognition; tagatose showed no significant associations.
The authors concluded that LNCS consumption was associated with accelerated cognitive decline over eight years, suggesting potential long-term adverse effects. Proposed mechanisms include neurotoxicity, neuroinflammation caused by toxic metabolites, and alterations in the gut microbiota. The researchers highlighted two study-specific limitations: a loss of nearly 75% of participants in completing all cognitive tests, and that the diet was assessed only at baseline and would not reflect subsequent changes.
This graphic shows that the highest tertiles of total sweetener consumption were more strongly associated with cognitive decline among participants with diabetes than among those without diabetes. This pattern suggests that the observed associations may not result directly from sweeteners but instead reflect the effects of diabetes, particularly when poorly managed.
Another noteworthy point concerns the relationship between tagatose and cognitive decline in participants with diabetes. Although tagatose showed no statistically significant adverse effects in most tests and may have even had neutral or potentially beneficial effects on overall cognition, the diabetic subsample exhibited a faster decline in executive function. This observation appears to contradict the researchers’ conclusion that more natural sweeteners may serve as suitable alternatives to LNCS.
Overall, considering these limitations, the evidence suggests that non-nutritive sweeteners remain generally safe. This is reassuring news, especially for those heading into the holiday season, armed with diet guaraná (arguably the best soda in Brazil) to wash down the turkey.
Sources: Brazilian Longitudinal Study of Adult Health (ELSA-Brasil): objectives and design. AM J. Epidemiol. DOI: 10.1093/aje/kwr294.
Examining the Usage Patterns of Non-Nutritive Sweeteners among Non-Diabetic Individuals: Insights from the Longitudinal Study of Adult Health (ELSA-Brasil). Nutrients. DOI: 10.3390/nu15224785.
Association Between Consumption of Low- and No-Calorie Artificial Sweeteners and Cognitive Decline. Neurology. DOI: 10.1212/WNL.0000000000214023
