Popular 'Natural' Sweetener Erythritol Found to Impair Brain Blood Vessels and Raise Stroke Risk in New Study

A widely used sugar substitute found in diet sodas, protein bars, keto snacks, and a growing range of processed foods marketed as "natural" may quietly damage the tiny blood vessels inside the brain, according to new research published in the Journal of Applied Physiology. Scientists at the University of Colorado Boulder exposed human brain microvascular endothelial cells — the specialized cells that line blood vessels in the brain — to erythritol concentrations equivalent to those produced in the body after consuming a typical sugar-free beverage. The results were troubling: the cells showed multiple dysfunction markers associated with elevated stroke risk, reduced blood flow regulation, and impaired clot-clearing ability.

Lead researchers Auburn R. Berry and Christopher A. DeSouza found that erythritol exposure caused brain vessel cells to produce substantially less nitric oxide, the molecule that signals blood vessels to relax and widen. At the same time, the cells produced more endothelin-1, a protein that causes vessel constriction. The combination — less vasodilation, more vasoconstriction — is a recognized signature of vascular dysfunction and is associated with hypertension and increased risk of ischemic stroke. The cells also showed significantly elevated levels of reactive oxygen species, the so-called free radicals that accelerate cellular aging, trigger inflammation, and damage vascular walls over time.

Perhaps most alarming was the finding about clot clearance. When exposed to thrombin — a substance that promotes clotting, normally present in the bloodstream — the erythritol-treated brain cells had a diminished ability to produce tissue plasminogen activator, or t-PA, the body's primary natural clot-dissolving enzyme. The same compound is used as a frontline emergency drug when patients arrive at hospitals with ischemic strokes caused by blood clots. A reduction in the brain's endogenous t-PA production could mean that small clots are less efficiently cleared, raising the risk of micro-infarcts and transient ischemic attacks — often called "mini-strokes."

Erythritol is a sugar alcohol that occurs naturally in small amounts in some fermented foods and in the human body as a metabolic byproduct of glucose. In commercial production, it is manufactured by fermenting glucose from wheat or corn starch. It has grown dramatically in market share over the past decade because it tastes similar to sugar, has essentially zero calories, does not spike blood sugar levels in the way that sugar or high-fructose corn syrup does, and was previously considered among the safer alternatives to both sugar and artificial sweeteners like aspartame and sucralose. The FDA classifies it as GRAS — generally recognized as safe — and it is heavily marketed to diabetics and people following low-carbohydrate diets.

The researchers were careful to note important limitations. Their study was conducted on isolated cells in a laboratory environment, not in living humans, and the concentrations used — while intended to mimic real-world exposure — may not precisely reflect what happens inside a functioning circulatory system. They called explicitly for human clinical trials before any firm public health conclusions are drawn. Still, the findings add to a growing body of evidence raising questions about erythritol's long-term cardiovascular safety. A 2023 study by Cleveland Clinic researchers published in Nature Medicine found a significant association between elevated erythritol blood levels and increased risk of heart attack and stroke in patients with existing cardiovascular risk factors. The new Colorado study provides a potential cellular mechanism that could help explain that association — and raises fresh questions about how broadly a sweetener consumed by millions of Americans every day has been evaluated for neurovascular effects.