The case for zero-calorie sweeteners has always rested on a simple trade: skip the sugar, avoid the metabolic consequences. Two studies published within the last year suggest that trade may not be as clean as it looks -- and that the brain may be paying part of the cost.
Higher sweetener consumption was linked to 62% faster cognitive decline.
A study published in Neurology, the journal of the American Academy of Neurology, followed 12,772 adults across Brazil for an average of eight years. Researchers tracked consumption of seven low- and no-calorie sweeteners -- aspartame, saccharin, acesulfame-K, erythritol, xylitol, sorbitol, and tagatose -- the same ones found in products like Diet Coke, Gatorade Zero, Halo Top, and Extra Gum. Participants completed dietary questionnaires and cognitive tests measuring verbal fluency, working memory, word recall, and processing speed at the start, middle, and end of the study.
People who consumed the highest amounts of sweeteners -- averaging 191 mg per day, roughly equivalent to one can of diet soda worth of aspartame -- showed a 62% faster rate of cognitive decline in overall thinking and memory than those consuming the lowest amounts (averaging 20 mg per day). The gap translated to approximately 1.6 additional years of brain aging. The middle group showed a 35% faster decline.
The effect was concentrated in adults under 60 and was stronger in participants with diabetes. No significant link was found in people over 60, and tagatose was the only sweetener that showed no association with cognitive decline.
"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 author Dr. Claudia Kimie Suemoto, MD, PhD, of the University of São Paulo.
The study was observational and does not establish causation. Diet was self-reported, and not every artificial sweetener on the market was included. But the consistency of the signal across six of the seven sweeteners examined -- and across eight years of follow-up -- is notable.
Erythritol specifically was found to damage the brain's protective barrier.
A separate study from the University of Colorado, Boulder, published in the Journal of Applied Physiology, focused specifically on erythritol -- a sugar alcohol increasingly used in keto and low-sugar products. Researchers exposed brain endothelial cells, the cells that make up the blood-brain barrier, to erythritol in laboratory conditions and observed a cascade of damaging effects.
Erythritol caused the cells to produce less nitric oxide, a compound that keeps blood vessels relaxed and dilated, while simultaneously increasing endothelin-1, a protein that constricts blood vessels. It also reduced the release of tissue plasminogen activator (t-PA), a compound that breaks down blood clots, and increased free radicals -- reactive oxygen molecules that damage tissue. Together, these changes tighten blood vessels, impair clot clearance, and leave the brain more vulnerable to ischemic stroke.
"Big picture, if your vessels are more constricted and your ability to break down blood clots is lowered, your risk of stroke goes up," said physiologist Auburn Berry. "Our research demonstrates not only that, but how erythritol has the potential to increase stroke risk."
The findings build on a prior epidemiological study that found higher erythritol blood levels were associated with increased risk of heart attack and stroke. The new lab research offers a potential biological mechanism for why.
Important caveats apply: this was a cell study, not a human trial, and the human body naturally produces small amounts of erythritol. It is possible elevated blood erythritol reflects an underlying metabolic condition rather than dietary intake alone. The researchers are clear that more clinical research is needed.
The sweetener that seems safe is often the one that hasn't been studied long enough.
The pattern here is familiar. Saccharin, aspartame, sucralose, and now erythritol have each been positioned at different points in time as the safe alternative -- approved, widely used, and defended as benign until a body of evidence accumulates suggesting otherwise. Erythritol in particular has been classified as a sugar alcohol, a category that exempted it from some of the scrutiny applied to other artificial sweeteners.
Dr. Suemoto's own conclusion gestures toward the real alternative: "More research is needed to investigate if other refined sugar alternatives, such as applesauce, honey, maple syrup or coconut sugar, may be effective alternatives."
The Animal Base Perspective: Real Sugar Over Fake Sugar
At AB, we don't carry processed sweeteners -- and this is exactly why. The argument for zero-calorie sweeteners has always been framed as risk reduction, but the studies keep reframing it as risk transfer: avoid glucose spikes, accept neurological trade-offs. The products we carry use real sugars in their whole form -- raw honey, fruit, unprocessed sources -- because the processing of any additive always comes with trade-offs the label does not disclose. Sugar consumption should still be calibrated to your activity level and metabolic health. But using real, whole-food sweeteners removes a layer of risk that the "zero-calorie" category is only beginning to account for.
