Common sugar substitute linked to brain blood vessel damage – higher heart attack and stroke risk

The popular sugar substitute erythritol, found in countless low-carb, keto, and “sugar-free” products, may come with hidden dangers. While it’s often seen as a healthier choice due to its low calorie count and minimal effect on blood sugar, new research from the University of Colorado Boulder suggests erythritol may damage the delicate cells that line blood vessels in the brain, potentially increasing the risk of stroke.

In a study published in the Journal of Applied Physiology, scientists treated human cerebral blood vessel cells with an amount of erythritol similar to what you'd find in a typical sugar-free drink. Within just three hours, those cells began to show signs of stress and dysfunction. The findings reveal a clear biological mechanism that may explain the troubling link between high erythritol levels in the blood and cardiovascular events like heart attacks and strokes.

“Our study adds to the evidence suggesting that non-nutritive sweeteners that have generally been purported to be safe may not come without negative health consequences,” said senior author Christopher DeSouza, professor of integrative physiology and director of the Integrative Vascular Biology Lab.

Led by DeSouza and graduate student Auburn Berry, the research team set out to understand why a previous large-scale study showed that people with higher levels of erythritol in their blood were significantly more likely to suffer from heart attacks or strokes within three years. That earlier study, involving over 4,000 individuals from the U.S. and Europe, found a strong connection even after adjusting for other common risk factors.

To explore this further, the Colorado team cultured human cerebral microvascular endothelial cells—those that line the small blood vessels in the brain—and exposed them to erythritol in amounts typical of one 12-ounce artificially sweetened drink (30 grams). After just three hours, several troubling changes were observed.

The cells produced significantly less nitric oxide, a molecule vital for relaxing and widening blood vessels. At the same time, they began making more endothelin-1, a protein that narrows blood vessels. This shift toward constriction increases resistance to blood flow and raises blood pressure—both known stroke risk factors.

Even more concerning, the cells released fewer molecules of t-PA, the compound responsible for breaking down blood clots. When blood clots form and the body's natural clot-busting system doesn’t respond effectively, the chance of a stroke rises sharply.

“Big picture, if your vessels are more constricted and your ability to break down blood clots is lowered, your risk of stroke goes up,” Berry explained. “Our research demonstrates not only that, but how erythritol has the potential to increase stroke risk.”

On a molecular level, the erythritol-exposed cells also showed more oxidative stress. That’s the buildup of reactive oxygen species—unstable molecules that damage cells, speed aging, and promote inflammation. The study found a 204% rise in these free radicals, along with significantly higher levels of antioxidant response proteins like superoxide dismutase-1 and catalase. These increases indicate that the cells were reacting defensively to high stress levels.

Even though the amount of endothelial nitric oxide synthase (eNOS)—the enzyme that makes nitric oxide—did not change much, its activity did. The cells had lower levels of a key activated form of the enzyme (p-eNOS Ser1177) and higher levels of an inactive version (p-eNOS Thr495), leading to reduced nitric oxide production overall. Without enough nitric oxide, vessels stay constricted and can’t properly regulate blood flow.

Furthermore, Big ET-1, a precursor to the vessel-constricting protein endothelin-1, was also elevated. The actual endothelin-1 levels jumped by nearly 30% in treated cells. Meanwhile, nitric oxide dropped significantly from 7.3 to 5.8 µmol/L. These shifts in vascular signaling push blood vessels toward a more dangerous, high-pressure state.

As a final test, the team simulated blood clot conditions using a compound called thrombin. In untreated cells, thrombin triggered a healthy increase in the release of t-PA. But in cells exposed to erythritol, this response was blunted. The release barely changed, staying at baseline levels, suggesting an impaired ability to prevent dangerous clots from forming.

Erythritol has been approved by the FDA since 2001 and is a favorite among those with diabetes or weight concerns. It's a sugar alcohol with about 0.2 calories per gram—roughly 80% as sweet as sugar—and doesn’t significantly raise blood sugar or insulin levels. It occurs naturally in small amounts in some fruits and vegetables, and is also produced inside the body by organs like the liver and kidney.

Because it’s absorbed quickly in the small intestine and excreted without much change, erythritol has long been considered safe. But mounting evidence is challenging that belief.

A study by Witkowski and colleagues used advanced metabolomic techniques to track erythritol in the blood. They found a strong association between high levels of this sweetener and increased platelet activity, which makes the blood more prone to clotting. These findings were consistent across different age groups, sexes, and ethnicities, and independent of other heart disease risk factors.

In small trials, healthy volunteers who consumed 30 grams of erythritol saw a rapid rise in blood erythritol and platelet reactivity. Within hours, their blood became more likely to form clots. These results raise serious concerns when combined with the new lab findings showing that erythritol weakens the body’s ability to counteract those clots.

“Given the epidemiological study that inspired our work, and now our cellular findings, we believe it would be prudent for people to monitor their consumption of non-nutrient-sweeteners such as this one,” said DeSouza.

Erythritol is a popular low-calorie sugar alcohol used in many "sugar-free" and "keto-friendly" products. It provides about 70% the sweetness of sugar but contains almost no calories.

Here’s a breakdown of some common food items and brands that use erythritol as a primary sweetener:

The research team cautions that their study was conducted in a lab using cell cultures, not in living humans. Still, the results provide a clear biological explanation for earlier studies that linked erythritol to heart and brain risks.

Since erythritol appears in so many processed foods, it’s easy to consume more than one serving a day without realizing it. DeSouza suggests reading nutrition labels carefully and watching for “erythritol” or “sugar alcohol” listed among the ingredients.

For now, the best path forward is moderation. Until more human trials are completed, it’s wise to limit intake of this and similar non-nutritive sweeteners—especially if you're at risk for cardiovascular issues.

Note: The article above provided above by The Brighter Side of News.

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