The popular sugar substitute erythritol, often promoted as a safe alternative for people managing obesity, diabetes, or metabolic conditions, may damage cells lining the brain’s blood vessels, according to a new laboratory study. The findings suggest a potential link between erythritol and increased risk of stroke, raising questions over the long-term use of this common sweetener in diet drinks and other low-calorie products.
Researchers exposed human brain microvascular endothelial cells to a dose of erythritol equivalent to that found in a single can of artificially sweetened beverage. Within hours, the cells showed a significant rise in oxidative stress, along with reduced nitric oxide production and impaired ability to regulate blood flow. These cellular changes are widely recognised as early markers of cerebrovascular dysfunction.
The study, published in the Journal of Applied Physiology, found that erythritol-treated cells produced around 75% more reactive oxygen species compared to untreated cells. This increase was accompanied by a rise in the production of antioxidant enzymes such as catalase and superoxide dismutase. While these enzymes normally protect cells from damage, their heightened activity suggested that the cells were responding to an abnormal level of stress.
Nitric oxide, which plays a key role in relaxing blood vessels and maintaining healthy circulation in the brain, was also significantly reduced. This was not due to a lack of the enzyme that produces nitric oxide, but rather a change in how the enzyme was activated. At the same time, levels of endothelin-1, a powerful vasoconstrictor that narrows blood vessels, increased. This imbalance between nitric oxide and endothelin-1 may impair cerebral blood flow and heighten stroke risk.
The researchers also looked at the cells’ ability to release tissue-type plasminogen activator (t-PA), a protein that helps dissolve blood clots. While untreated cells responded to a trigger by increasing t-PA release, the erythritol-treated cells showed no such response, suggesting weakened protection against thrombosis.
This in vitro research builds on recent large-scale population studies that have associated higher erythritol levels in the blood with increased rates of cardiovascular and cerebrovascular events. While the study does not prove that erythritol causes stroke in humans, the results support concerns that the sweetener may disrupt vascular function at a cellular level.
The findings may be especially relevant for individuals who consume multiple diet drinks a day. Erythritol is widely used not only in beverages, but also in baked goods, sugar-free gum, and protein bars. Though it occurs naturally in small amounts in fruit, commercially produced erythritol is often consumed in much higher concentrations.
Because the study was conducted in a controlled laboratory setting, the researchers caution that it does not confirm direct health outcomes in people. Still, the cellular effects observed are consistent with known mechanisms involved in stroke and other vascular disorders, and they call for further investigation through clinical trials.