Erythritol, a common non-nutritive sweetener, is associated with increased risk of cardiovascular and cerebrovascular events, according to new research from the University of Colorado, Boulder.
Berry et al. demonstrate that erythritol — at a concentration typically contained in a standard-size commercially available artificially sweetened beverage — adversely affects brain microvascular endothelial cell oxidative stress, eNOS activation and NO production, ET-1 expression, and t-PA release in vitro. Image credit: Tafilah Yusof.
Erythritol is a widely used non-nutritive sugar substitute due to its minimal impact on blood glucose and insulin levels.
A 4-carbon sugar with extremely low-calorie content, erythritol, is around 60-80% as sweet as sucrose, making it a popular sugar substitute/artificial sweetener in baked goods, confectionary products, and beverages.
Approved by the FDA in 2001, the use of erythritol has been advocated for individuals with obesity, metabolic syndrome, and diabetes to help regulate/reduce caloric consumption and sugar intake as well as help limit high blood glucose levels.
Erythritol occurs naturally in low amounts in several types of fruits and vegetables as well as fermented foods and is rapidly absorbed by the small intestine via passive diffusion.
In humans, erythritol is also produced endogenously from glucose and fructose by erythrocytes, liver, and kidney through the pentose phosphate pathway. Thus, circulating erythritol levels are affected by both endogenous production and exogenous intake.
“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 University of Colorado, Boulder’s Professor Christopher DeSouza.
In a recent study involving 4,000 people in the U.S. and Europe, scientist found that men and women with higher circulating levels of erythritol were significantly more likely to have a heart attack or stroke within the next three years.
Professor DeSouza and his colleagues set out to understand what might be driving that increased risk.
They treated human cells that line blood vessels in the brain for three hours with about the same amount of erythritol contained in a typical sugar-free beverage.
They observed that the treated cells were altered in numerous ways.
The cells expressed significantly less nitric oxide, a molecule that relaxes and widens blood vessels, and more endothelin-1, a protein that constricts blood vessels.
Meanwhile, when challenged with a clot-forming compound called thrombin, cellular production of the natural clot-busting compound t-PA was ‘markedly blunted.’
The erythritol-treated cells also produced more reactive oxygen species, or free radicals, metabolic byproducts which can age and damage cells and inflame tissue.
“Big picture, if your vessels are more constricted and your ability to break down blood clots is lowered, your risk of stroke goes up,” said Auburn Berry, a graduate student at the University of Colorado, Boulder.
“Our research demonstrates not only that, but how erythritol has the potential to increase stroke risk.”
“Our study used only a serving-size worth of the sugar substitute,” Professor DeSouza said.
“For those who consume multiple servings per day, the impact, presumably, could be worse.”
The authors caution that their study was a laboratory study, conducted on cells, and larger studies in people are needed.
That said, they encourage consumers to read labels, looking for erythritol or ‘sugar alcohol’ on the label.
“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,” Professor DeSouza said.
The study was published today in the Journal of Applied Physiology.
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Auburn R. Berry et al. 2025. The non-nutritive sweetener erythritol adversely affects brain microvascular endothelial cell function. Journal of Applied Physiology 138 (6): 1571-1577; doi: 10.1152/japplphysiol.00276.2025