This Popular Zero-Calorie Sweetener Could Impair Brain Blood Vessel Cells, Study Suggests

Lab Study Raises Concerns That Sugar Substitute Erythritol May Raise Risk of Stroke

By StudyFinds Analysis

July 16, 2025

BOULDER, Colo. — That zero-calorie sweetener making your morning coffee taste just right might be quietly interfering with the tiny blood vessels in your brain — at least in a petri dish.

A new laboratory study has found that erythritol, one of the most widely used artificial sweeteners, adversely affects the function of human brain blood vessel cells at levels similar to drinking just one can of diet soda.

Researchers from the University of Colorado-Boulder discovered that erythritol triggers a cascade of cellular changes that could theoretically raise stroke risk: ramping up harmful oxidative stress inside cells, disrupting protective nitric oxide pathways, and blunting the brain’s natural clot-busting abilities.

The team used concentrations of erythritol that match what someone would have in their bloodstream after consuming about 30 grams of the sweetener, which is roughly the amount in a standard artificially sweetened drink.

It’s the same kind millions of people reach for daily, believing they’re making a healthier choice because it says “diet” or “sugar-free.”

Erythritol’s popularity has surged over the past decade as consumers and food companies search for sugar alternatives that don’t spike blood sugar levels.

Found in everything from sugar-free gum and protein bars to energy drinks and low-calorie sodas, erythritol occurs naturally in some fruits but is now produced industrially for commercial use.

The U.S. Food and Drug Administration approved it in 2001, and it’s marketed as a nearly ideal sugar substitute: it tastes about 60–80% as sweet as sugar, provides virtually no calories, and is generally considered safe for people with diabetes.

How Erythritol Alters Brain Vessel Cells

Researchers from the University of Colorado Boulder focused on human brain microvascular endothelial cells.

These are specialized cells that line the tiny blood vessels in the brain.

They are vital gatekeepers of the blood-brain barrier, regulating blood flow and blocking harmful substances from reaching brain tissue.

In the experiment, the team exposed these cells to a 6 millimolar (mM) concentration of erythritol for three hours — a dose that mimics typical human blood levels after consuming about 30 grams of the sweetener.

The results were striking: erythritol increased the production of reactive oxygen species (ROS) — a form of harmful cellular stress — by about 75%.

It also disrupted the cells’ ability to produce nitric oxide, a protective molecule that keeps blood vessels open and healthy.

Nitric oxide production dropped by around 20% in the erythritol-treated cells.

At the same time, levels of endothelin-1 (a powerful blood vessel constrictor) rose by about 30%. Tight regulation of blood vessel diameter is especially crucial in the brain, where steady blood flow is needed to keep neurons alive.

Perhaps most concerning was erythritol’s impact on the brain’s natural clot-busting system.

When the researchers exposed the cells to thrombin, a protein that normally triggers the release of tissue plasminogen activator (t-PA) to dissolve clots, the untreated cells boosted their t-PA release by about 25%.

But the erythritol-treated cells failed to respond at all.

A Recipe for Stroke?

The authors note that these cellular changes represent “central characteristics of cerebral vascular endothelial dysfunction and causative factors in the development, severity, and outcome of ischemic stroke.”

Ischemic stroke — which happens when a clot blocks blood flow to part of the brain — accounts for nearly 87% of all strokes.

The combination of increased cellular stress, reduced nitric oxide, elevated endothelin-1, and impaired clot-busting ability could, in theory, create conditions that increase the risk of these dangerous blockages.

Researchers point out that brain blood vessels are especially vulnerable to this kind of damage because they contain large numbers of mitochondria, the tiny energy factories inside cells that are particularly sensitive to oxidative stress.

Is It Time To Substitute Sugar Subtitutes?

These results, published in the Journal of Applied Physiology, are noteworthy given how common erythritol is and the mounting evidence linking it to cardiovascular issues.

Recent large-scale studies have found that people with elevated blood levels of erythritol had a higher risk of heart attacks and strokes over three years.

A small follow-up trial showed that consuming 30 grams of erythritol significantly increased platelet activity and clotting potential in healthy volunteers.

Unlike some cell studies that use unrealistically high doses, this research used erythritol levels that millions of people can realistically reach through normal consumption of sugar-free foods and drinks.

Still, the researchers acknowledge that the study has important limitations: it was conducted in isolated cells over a short period and does not prove that consuming erythritol causes strokes in real people.

However, the cellular pathways they identified have been linked to stroke risk in other studies and provide a plausible mechanism worth investigating further.

Rethinking Erythritol

Erythritol’s rise from a niche ingredient to a mainstream sugar substitute reflects a broader trend: as obesity rates rise and more people try to manage diabetes, artificial sweeteners have become go-to products for cutting calories without giving up sweetness.

Marketing often highlights the positives, noting that erythritol is “natural,” low-calorie, and doesn’t upset the gut the way other sugar substitutes can.

But emerging research on its potential cardiovascular and cerebrovascular effects receives far less attention.

For now, this new evidence suggests that while erythritol may still have a place for people managing diabetes or weight, it may not be the entirely risk-free alternative it’s sometimes made out to be.

Instead of searching for the perfect artificial sugar substitute, many health experts argue that training our palates to crave less sweetness overall — from any source — could be a healthier long-term strategy.

Disclaimer: This report summarizes the findings of an in vitro (lab-based) study. The research did not test erythritol’s effects in living humans, so it does not prove that consuming erythritol causes stroke or other health problems. Always consult qualified health professionals for advice about your diet and health choices.