Common sugar substitute linked to stroke-related brain effects, study finds

University of Colorado Boulder researchers document how the zero-calorie sweetener triggers cellular changes in brain vessels that may increase clotting and reduce blood flow.

Erythritol appears in countless sugar-free products, from diet sodas to protein bars, marketed as a safe alternative for managing weight and blood sugar. New laboratory research published in the Journal of Applied Physiology in July 2025 reveals the popular sweetener triggers concerning changes in the cells lining brain blood vessels, potentially elevating stroke risk through multiple biological mechanisms.

Professor Christopher DeSouza, who led the University of Colorado Boulder study, emphasizes that the findings challenge assumptions about artificial sweetener safety. The research demonstrates that non-nutritive sweeteners generally promoted as harmless may carry unexpected health consequences, according to the study team.

How researchers tested the sweetener's effects

The Colorado research team focused specifically on endothelial cells, which form the inner lining of blood vessels throughout the brain. These cells perform critical functions including regulating blood flow, controlling inflammation, and preventing dangerous clot formation.

Scientists exposed these brain vessel cells to erythritol concentrations equivalent to consuming a single sugar-free beverage. The exposure lasted just three hours. This brief contact period produced measurable cellular dysfunction across multiple pathways that protect against stroke.

Oxidative stress overwhelms cellular defenses

The erythritol exposure triggered significant oxidative stress within the cells. Reactive oxygen species, unstable molecules that damage cellular structures including DNA and proteins, flooded the cells. While the cells attempted to mount antioxidant defenses in response, these protective mechanisms proved insufficient to counter the assault.

First author Auburn Berry notes that the research demonstrates not only the potential for erythritol to increase stroke risk, but specifically identifies the biological mechanisms through which this occurs. The cellular stress response indicated the sweetener created conditions that favor vascular dysfunction.

Blood vessel relaxation capacity declines sharply

Nitric oxide serves as a crucial signaling molecule that helps blood vessels dilate and maintain proper blood flow to the brain. The study documented that erythritol exposure reduced nitric oxide production by approximately 20 percent compared to untreated cells.

The mechanism involved disruption of the enzyme responsible for generating nitric oxide. While total enzyme levels remained relatively stable, its functional activity dropped substantially. The sweetener interfered with the enzyme's activation at two specific molecular sites, ultimately compromising the vessels' ability to relax when needed.

Vessel constriction signals increase dramatically

Simultaneously, the erythritol-exposed cells ramped up production of endothelin-1, a protein that signals blood vessels to constrict. Treated cells showed a 30 percent increase in this vessel-tightening compound compared to normal cells. Levels of its precursor molecule also rose significantly.

Berry explains that the combination creates particularly dangerous conditions. When vessels lose their capacity to widen while simultaneously receiving intensified signals to narrow, stroke risk climbs. This dual effect restricts blood flow precisely when the brain requires steady circulation.

Clot breakdown mechanisms fail to activate

The body relies on tissue-type plasminogen activator to dissolve blood clots that form inappropriately inside vessels. Researchers tested whether erythritol affected this protective system by adding thrombin, which mimics natural clotting signals.

Normal cells responded to thrombin with a 25 percent increase in clot-dissolving enzyme release. Erythritol-treated cells showed no response whatsoever. The complete absence of this critical safety mechanism means clots could form without the body mounting its standard defensive reaction.

Human population data supports cellular findings

The laboratory results align with earlier epidemiological research published in Nature Medicine in February 2023. That Cleveland Clinic study, led by Dr. Stanley Hazen, tracked more than 4,000 people across the United States and Europe. Individuals with elevated blood erythritol levels experienced higher rates of heart attacks and strokes within three years, regardless of gender or pre-existing health conditions.

The Colorado team's cellular research provides biological explanations for the patterns observed in human populations. The documented mechanisms of vessel dysfunction, impaired relaxation, increased constriction, and failed clot breakdown directly correspond to stroke pathology seen in the Cleveland Clinic findings.

What's next for sweetener consumption

DeSouza emphasizes that given both the epidemiological evidence and the new cellular findings, prudent consumers should monitor their intake of non-nutritive sweeteners like erythritol. The study examined acute effects from a single serving, but many people consume multiple servings daily.

Unlike some substances that cannot enter the brain, erythritol crosses the blood-brain barrier. The research focused on short-term exposure, but questions remain about cumulative effects from repeated daily consumption. The study findings suggest long-term investigation into chronic exposure effects represents an important next step for understanding the full health implications of widespread erythritol use.