Are Artificial Sweeteners Not Only Damaging Our Intestines, But Our Brain, As Well?

By Wayne Persky

RSS Feed

A major new study links popular sweeteners to faster cognitive decline. For microscopic colitis (MC) patients, there's a second layer of risk that most coverage isn't mentioning.

Many of us turned to artificial sweeteners and sugar alcohols years ago, to manage weight, control blood sugar, reduce calories, or simply because we were told they were a safer alternative to sugar. A major new study published in Neurology, the journal of the American Academy of Neurology, suggests that for at least some of those sweeteners, the "safer" assumption may have been wrong. And for MC patients, the concerns go beyond the brain.

What the new study found:

Researchers at the University of Sao Paulo followed nearly 13,000 Brazilian adults with an average age of 52 for approximately eight years, tracking their consumption of seven widely used low- or no-calorie sweeteners and monitoring their cognitive function through repeated assessments of verbal fluency, working memory, word recall, and processing speed (American Academy of Neurology, 2025, September 3).1

The results were striking. People who consumed the largest total amounts of sweeteners experienced a 62% faster decline in overall thinking and memory abilities than those who consumed the least — a difference the researchers estimated was comparable to roughly 1.6 additional years of cognitive aging. Even those in the middle consumption group experienced a 35% faster decline, equivalent to about 1.3 extra years of aging.

The association was especially pronounced in adults under 60, and was stronger in people with diabetes than in those without it. Since people with diabetes are among the most frequent users of sugar substitutes (because they're advised to use them specifically to manage blood sugar) this finding is particularly significant.

The seven sweeteners studied were aspartame, saccharin, acesulfame K, erythritol, xylitol, sorbitol, and tagatose. Six of the seven — all except tagatose — were associated with faster cognitive decline. The researchers were careful to note that this was an observational study and could not prove that sweeteners caused the cognitive changes. Other factors could help explain the pattern. But the consistency and size of the association across nearly 13,000 people over eight years is not something to dismiss lightly.

Why might sweeteners affect the brain?

The mechanisms aren't fully established, but several plausible pathways have been proposed in the research literature.

Aspartame is metabolized into methanol and then formaldehyde in the body, which can generate free radicals and oxidative stress. Some animal studies have found that aspartame at relatively low doses causes abnormalities in brain chemistry and learning deficits, and there is evidence that it may be able to breach the blood-brain barrier under some conditions (Ravn, 2025, October 10).2 Aspartame also produces phenylalanine as a breakdown product, which in large amounts can affect neurotransmitter balance.

A second and increasingly important pathway involves the gut-brain axis. Research has established that the gut microbiome communicates continuously with the brain through neural, immune, and endocrine signaling pathways. Disruption of the gut microbiome (called dysbiosis) can compromise the intestinal barrier, increase systemic inflammation through the release of bacterial endotoxins into the bloodstream, and trigger neuroinflammation that impairs cognitive function (Tana, Moffa, Tana, Ucciferri, and Moffa, 2025; Rundek et al. 2021).3, 4 Several artificial sweeteners, particularly sucralose and saccharin, have demonstrated bacteriostatic effects on gut bacteria, meaning they inhibit bacterial growth and can alter the composition of the microbiome in ways that tip it toward a pro-inflammatory state (Basson, Rodriguez-Palacios, and Cominelli, 2021; Xiaofa, 2014).5, 6​

This gut-brain pathway is especially relevant to MC patients,

as we'll discuss below.

What we know about the specific sweeteners:

Aspartame:
Found in diet sodas, many flavored drinks, tabletop sweeteners like Equal and NutraSweet, and thousands of processed food products. It was the sweetener most commonly discussed in the new Brazilian study's high-consumption group, and earlier research has linked it to oxidative stress and neurochemical changes in animals. The amount consumed by the highest intake group in the study was roughly equivalent to the aspartame in one can of diet soda per day.

Saccharin:
One of the oldest artificial sweeteners, found in Sweet'N Low and many processed foods. Epidemiological data from several countries has shown that spikes in IBD incidence have followed regulatory approval of saccharin in their markets — a correlation that has been noted in academic literature as potentially more than coincidental. Saccharin has demonstrated inhibitory effects on intestinal bacteria, and its decline in use in the late 1970s and early 1980s following cancer concerns was followed by a decrease in IBD rates in some regions.

Acesulfame K:
A high-intensity sweetener frequently used in combination with aspartame or sucralose to improve flavor in diet beverages and processed foods. It was among the six sweeteners associated with cognitive decline in the new study.

Sorbitol:
A sugar alcohol found naturally in some fruits and used widely in sugar-free candies, gum, baked goods, and medications. It was consumed in the largest quantity of any individual sweetener among the Brazilian study's participants, averaging 64 mg per day in the overall population. Sorbitol is also a well-established osmotic laxative — it draws water into the colon, which can cause bloating, cramping, and diarrhea even in people with healthy digestive systems (Mäkinen, 2016).7 For MC patients, this effect is relevant and serious.

Xylitol:
Another sugar alcohol, common in sugar-free gum, mints, and dental products. Like sorbitol, it's poorly absorbed in the small intestine, reaches the colon largely intact, and can cause osmotic diarrhea in sensitive individuals. Recent cardiovascular research has also raised concerns about xylitol's effects on platelet reactivity, suggesting potential links to increased clotting risk (Witkowski et al., 2023).8

Erythritol:
Generally considered the best-tolerated sugar alcohol from a gastrointestinal standpoint because most of it is absorbed in the small intestine before reaching the colon, minimizing the osmotic diarrhea effect that makes sorbitol and xylitol problematic. However, it was still among the six sweeteners linked to cognitive decline in the new study, and at high doses it can still cause nausea, bloating, and loose stools.

Tagatose:
The one sweetener in the study that was not associated with cognitive decline, and the exception is notable because tagatose has a meaningfully different biological profile from the others. It has a glycemic index of just 3 (compared to 65 for table sugar), acts as a prebiotic by generating short-chain fatty acids in the gut, and may actually support beneficial gut bacteria rather than disrupting them (Spinner, 2024, September 5; Durante et al., 2021).9, 10 Researchers at Tufts University recently developed a more efficient production method for tagatose, which may make it more widely available and affordable. It is already FDA-designated as generally recognized as safe (Love et al., 2025).11 For MC patients who need a sweetener, tagatose appears to be the most promising option currently available, although large quantities may still cause some GI discomfort in susceptible individuals, and human evidence on long-term effects remains limited.​

The particular risks for MC patients:

For most people, the cognitive findings in this study are the central concern. For MC patients, there's a second layer of risk that has received almost no attention in news coverage of the study. Several of these sweeteners have documented adverse effects on the gut that are especially dangerous for people with inflammatory bowel disease.

Sucralose, one of the most widely used sweeteners in the world, though not among the seven specifically studied in the new Brazilian research, has been shown in multiple animal studies to worsen gut inflammation in models of IBD, including both Crohn's disease and ulcerative colitis. It promotes dysbiosis, increases inflammatory markers, weakens the gut barrier, and stimulates the development of colonies of-invasive E. coli — the same pathogenic bacteria linked to soybean oil's effects on the gut (Rodriguez-Palacios et al., 2018).12 Research has also shown that sucralose worsens gut damage and promotes colitis-associated colorectal cancer risk in animal models (Li et al., 2020).13 About 10% to 15% of IBD patients report that artificial sweeteners worsen their symptoms — a figure that almost certainly understates the true proportion, since many patients don't connect their sweetener use to their symptoms.

Saccharin and acesulfame K have also been linked to IBD promotion through their inhibitory effects on intestinal bacteria. The concern is that these sweeteners remain in the gastrointestinal tract for extended periods, inhibit bacterial growth, reduce the bacterial populations that normally inactivate digestive proteases in the lower gut, and may thereby contribute to the protease-driven intestinal damage that's a feature of IBD pathogenesis.

Sorbitol and xylitol carry direct osmotic risks for MC patients. Both are classified as FODMAPs — fermentable carbohydrates that are poorly absorbed and highly fermentable in the colon. For someone whose gut is already compromised and whose colon responds to osmotic challenges with diarrhea and urgency, even moderate amounts of these sugar alcohols can trigger or worsen symptoms. Sorbitol in particular is a medically recognized laxative; it's not a dietary option that MC patients can safely use without caution.

The gut-brain connection adds another dimension. Research has increasingly established that gut dysbiosis can drive neuroinflammation through the gut-brain axis — that is, a disrupted and inflamed gut can contribute to cognitive impairment through systemic inflammation that reaches the brain. MC patients already have a disrupted gut environment and often experience brain fog that correlates with disease activity. Sweeteners that further disrupt the gut microbiome could theoretically worsen both gut symptoms and the cognitive effects they contribute to — a compounding problem rather than two separate ones.​

What about natural sweeteners?

The Brazilian study's lead author specifically noted that more research is needed on alternatives such as applesauce, honey, maple syrup, and coconut sugar.1 None of those were studied, and for MC patients some of them carry their own risks depending on individual tolerance. Honey and maple syrup contain fructose and other sugars that can be problematic during flares. Applesauce is tolerated by many MC patients but contains sorbitol naturally — a consideration for those who are particularly sensitive.

Stevia and monk fruit were not included in the Brazilian study and were not among the sweeteners linked to cognitive decline. Neither has been associated with the gut dysbiosis effects documented for sucralose and saccharin, though animal research on stevia and the gut microbiome has produced mixed results that are not yet conclusive in humans. For MC patients who need a sweetener during remission, stevia appears to be one of the lower-risk options based on current evidence, as does tagatose — with the caveat that large amounts of either may not be well tolerated by everyone.

The practical message for MC patients:

The picture that emerges from this research is that most of the commonly used sugar substitutes carry risks we weren't fully informed about when we started using them. Six of the seven sweeteners examined in a rigorous eight-year study of nearly 13,000 people were associated with measurable cognitive decline. Several of those same sweeteners have independent evidence linking them to gut dysbiosis, worsened IBD symptoms, and intestinal barrier damage. And the population most frequently advised to use sugar substitutes — people with diabetes — is the same population in which the cognitive effects appear to be strongest.

For MC patients, this isn't an abstract concern. Many of us use these sweeteners daily in beverages, medications, and processed foods, often without realizing they're there. They appear on labels under multiple names and are present in products that don't advertise themselves as sugar-free.

The most practical steps we can take are to read labels carefully and identify which sweeteners we're currently consuming, give particular priority to avoiding sorbitol, xylitol, saccharin, sucralose, and acesulfame K, consider shifting to tagatose or stevia as primary sweeteners if we need one, and discuss with our care team whether our current sweetener use is consistent with our gut health goals.
​
As with so many things in MC management, the safest approach is the most whole-foods-based one — meaning that reducing our dependence on sweetened products of any kind, artificial or otherwise, is probably the most protective step we can take for both our gut and our brain.

References:

1. American Academy of Neurology. (2025, September 3). Study links high intake of artificial sweeteners to faster cognitive decline. Retrieved from https://www.news-medical.net/news/20250903/Study-links-high-intake-of-artificial-sweeteners-to-faster-cognitive-decline.aspx

2. Ravn, C. (2025, October 10). Does Aspartame Cause Demential? Memory Loss, Sweeteners & Daily Impact. Retrieved from https://optoceutics.com/does-aspartame-cause-dementia-alzheimers-memory-loss-artificial/?srsltid=AfmBOopUu25hEibVByI5O-F93d6bWxJT3mS80vs5FkdYTYF-sYYJRxdt

3. Tana, C., Moffa S, Tana, M., Ucciferri, C., and Moffa, L. (2025). Gut Microbiota, Mild Cognitive Impairment and Dementia: A Systematic Review. Neurology International, 17(10). 155. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC12566805/

4. Rundek, T., Roy, S., Hornig, M., Cheung, Y. K., Gardener, H., DeRosa, J., . . . Sacco, R. L. (2021). Gut permeability and cognitive decline: A pilot investigation in the Northern Manhattan Study. Brain Behavior & Immunity — Health, 12:100214. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC8186438/

5. Basson, A. R., Rodriguez-Palacios, A., and Cominelli, F. (2021). Artificial Sweeteners: History and New Concepts on Inflammation. Frontiers in Nutrition, 8:746247. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC8497813/

6. Xiaofa, Q. (2014). May artificial sweeteners not sugar be the culprit of dramatic increase of inflammatory bowel disease in China? Chinese Medical Journal, 127(17) Retrieved from https://mednexus.org/doi/pdf/10.3760/cma.j.issn.0366-6999.20140673

​7. Mäkinen, K. K. (2016). Gastrointestinal Disturbances Associated with the Consumption of Sugar Alcohols with Special Consideration of Xylitol: Scientific Review and Instructions for Dentists and Other Health-Care Professionals. International Journal of Dentistry, 2016:5967907. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC5093271/

8. Witkowski, M., Nemet, I., Alamri, H., Wilcox, J., Gupta, N., Nimer, N., . . . Hazen, S. L. (2023). The artificial sweetener erythritol and cardiovascular event risk. Nature Medicine, 29, pp 710–718. Retrieved from https://www.nature.com/articles/s41591-023-02223-9

9. Spinner, J. (2024, September 5). Tagatose sweetens with prebiotic benefits: ASR Group. Snack Food & Wholesale Bakery, Retrieved from https://www.snackandbakery.com/articles/112030-tagatose-sweetens-foods-with-lower-gi-and-prebiotic-benefits-asr-group

10. Durante, M., Sgambellone, S., Lucarini, L., Failli. P., Laurino, A., Collotta, D., . . . Collino, M. (2021). D-Tagatose Feeding Reduces the Risk of Sugar-Induced Exacerbation of Myocardial I/R Injury When Compared to Its Isomer Fructose. Frontiers in Molecular Biosciences, 8:650962. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC8076855/

11. Love, A., Toomey, C., Kumar, A., Kashyap, S. N., Santhamoorthy, D. K., Muthuraj, L., . . . Santos, C. N. S. (2025). Reversal of the Leloir pathway to promote galactose and tagatose synthesis from glucose. Cell Reports Physical Science, 6(12). 102993. Retrieved from https://www.cell.com/cell-reports-physical-science/fulltext/S2666-3864(25)00592-2

12. Rodriguez-Palacios, A., Harding, A., Menghini, P., Himmelman, C., Retuerto, M., Nickerson, K. P., . . . Cominelli, F. (2018). The Artificial Sweetener Splenda Promotes Gut Proteobacteria, Dysbiosis, and Myeloperoxidase Reactivity in Crohn's Disease-Like Ileitis. Inflammatory Bowel Diseases, 24(5). pp 1005–1020. Retrieved from https://pubmed.ncbi.nlm.nih.gov/29554272/

13. Li, X., Liu, Y., Wang, Y., Li, X., Liu, X., Guo, M., . . . Jiang, M. (2020). Sucralose Promotes Colitis-Associated Colorectal Cancer Risk in a Murine Model Along With Changes in Microbiota. Frontiers in Oncology, 10:710. Retrieved from https://pubmed.ncbi.nlm.nih.gov/32582527/