March 14, 2023

Erythritol and cardiovascular events

At a Glance

  • Higher blood levels of the artificial sweetener erythritol were associated with increased risk of heart attack and stroke.
  • The results highlight the need for further study of erythritol’s long-term risks for cardiovascular health.
Woman selecting groceries from a shelf. Erythritol is found in many foods and drinks, but is not required to be listed on nutrition labels. Prostock-studio / Shutterstock

Artificial sweeteners have become a widespread way to reduce sugar and calorie intake. Regulatory agencies generally consider artificial sweeteners to be safe. But little is known about their long-term health consequences. Growing evidence points to a link between certain artificial sweeteners and cardiovascular problems. But the connection hasn’t yet been proven.

Erythritol is a common artificial sweetener. Low amounts occur naturally in fruits and vegetables. It is also made inside our cells as part of normal metabolism. But when used as a sweetener, erythritol levels are typically more than 1,000-fold greater than levels found naturally in foods. Erythritol is in an ingredient category called “sugar alcohols,” which are not required to be listed individually on Nutrition Facts labels. 

An NIH-funded research team led by Dr. Stanley Hazen at the Cleveland Clinic examined the relationship between erythritol and heart attacks and stroke. In an initial study with more than 1,000 people, the team looked for compounds in blood whose levels were linked to future cardiac risk. They tracked major adverse cardiovascular events over three years, including death and nonfatal heart attack or stroke. Results appeared in Nature Medicine on February 27, 2023.

The team found that elevated levels of erythritol and several related artificial sweeteners were associated with the risk for cardiovascular events. To confirm this result, the researchers examined two more groups of people in the U.S. and Europe totaling almost 3,000. They also developed a method to better distinguish erythritol from related compounds.

These measurements reproduced the association between erythritol and cardiovascular events. People with the highest erythritol levels (top 25%) were about twice as likely to have cardiovascular events over three years of follow-up as those with the lowest (bottom 25%).

Next, the team wanted to better understand how erythritol might increase these health risks. So, they exposed human platelets, which control blood clotting, to erythritol. Doing so increased the platelets’ sensitivity to blood clotting signals. Increasing blood erythritol levels also sped up blood clot formation and artery blockage in mice.

The scientists next asked how diet affects erythritol levels in people. To find out, they measured blood erythritol levels in eight healthy volunteers after drinking a beverage sweetened with erythritol. Blood erythritol levels increased 1,000-fold and remained substantially elevated for several days. For at least two days, the erythritol levels grew more than high enough to trigger changes in platelet function.

These results suggest that consuming erythritol can increase blood clot formation. This, in turn, could increase the risk of heart attack or stroke. Given the prevalence of erythritol in artificially sweetened foods, further safety studies of the health risks of erythritol are warranted.

“Sweeteners like erythritol have rapidly increased in popularity in recent years, but there needs to be more in-depth research into their long-term effects,” Hazen says. “Cardiovascular disease builds over time, and heart disease is the leading cause of death globally. We need to make sure the foods we eat aren’t hidden contributors.”

—by Brian Doctrow, Ph.D.

Related Links

References: The artificial sweetener erythritol and cardiovascular event risk. Witkowski M, Nemet I, Alamri H, Wilcox J, Gupta N, Nimer N, Haghikia A, Li XS, Wu Y, Saha PP, Demuth I, König M, Steinhagen-Thiessen E, Cajka T, Fiehn O, Landmesser U, Tang WHW, Hazen SL. Nat Med. 2023 Feb 27. doi: 10.1038/s41591-023-02223-9. Online ahead of print. PMID: 36849732.

Funding: NIH’s National Heart, Lung, and Blood Institute (NHLBI) and Office of Dietary Supplements (ODS); Leducq Foundation; Deutsche Forschungsgemeinschaft; Charité—Universitätsmedizin Berlin; Berlin Institute of Health; Sanofi-Aventis Deutschland GmbH; American Heart Association.