Research News

New Cleveland Clinic-led research demonstrates the artificial sweetener erythritol’s potential to cause blood clots in a human study. Healthy participants drank water sweetened with either 30 grams of erythritol or 30 grams of glucose (sugar)—less than the amount typically found in a sugar-sweetened can of soda.

What is erythritol?

Erythritol, a common artificial sweetener, has become one of the most popular in the class that is known as sugar alcohols. Low amounts of erythritol occur naturally in fruits and vegetables. Erythritol products like low-calorie, low-carbohydrate, “zero sugar” and “keto” foods (including sugar-free chocolate bars and ice creams, zero-calorie sodas and even packaged keto snacks) substitute the sweetener for table sugar.

Although artificial sweeteners like erythritol are generally considered safe, researchers are still studying both short-term and long-term side effects. “Many professional societies and clinicians routinely recommend that people at high cardiovascular risk—those with obesity, diabetes or metabolic syndrome—consume foods that contain sugar substitutes rather than sugar,” explains Stanley Hazen, MD, PhD.

Since people with these conditions are already at a higher risk for developing adverse cardiovascular events like heart attack or stroke, Dr. Hazen says he felt it critical as a clinician to perform more research after his 2023 study found that erythritol was clinically associated with higher chance of a major adverse cardiac event, and in mechanistic (blood and preclinical model) studies provoked enhanced thrombosis potential.

Testing erythritol dangers and side effects

Dr. Hazen led the research team performing the studies published in Arteriosclerosis, Thrombosis and Vascular Biology. His lab conducted the precursor study in 2023 which first highlighted erythritol dangers, and demonstrated that elevated blood erythritol levels are associated with an increased risk of cardiovascular events like heart attack or stroke. The study was designed to directly compare the effects of ingesting erythritol versus an equivalent amount of regular sugar on platelets—disc-shaped blood cells that play a critical role in forming blood clots.

The study’s 20 healthy volunteers had their blood drawn following an overnight fast to assess baseline measurements. After subsequently consuming water mixed with either 30 grams of erythritol or 30 grams of sugar, blood was drawn again after 30 minutes to measure plasma levels and multiple measures of platelet function.

Blood levels of erythritol increased more than 1,000-fold after consuming the erythritol-sweetened drink, compared to baseline measurements. In every subject, platelet aggregation responses and other measures of platelet reactivity strikingly increased after consuming erythritol but did not change after participants consumed sugar. For every test of platelet function measured, and in every subject, the platelets after exposure to the erythritol drink appeared to be “aggravated,” and therefore more prone to clotting and causing thrombosis. Drinking the comparable sugar-sweetened drink failed to provoke any changes in functional testing.

The findings contribute to Dr. Hazen’s team’s ongoing investigation into the effects of sugar substitutes on the body’s systems. Although our bodies naturally create low levels of erythritol, this study further demonstrates the implications when the sugar substitute accumulates to excessive levels.

To avoid health risks, choose sugar over artificial sweeteners—in moderation

Study co-author W.H. Wilson Tang, MD says the erythritol intervention study is especially notable following the team’s recently published findings on xylitol, another artificial sweetener. In that study, ingestion of a solution containing 30 grams of xylitol—another sugar alcohol used in diabetic candies and confections, oral care products, and like erythritol, to sweeten food and beverages—produced similar increases in plasma levels and similar acute effects on platelet aggregation in healthy volunteers. The study from Dr. Hazen’s lab, however, was a different design. In addition to looking at each subject before versus after ingestion, this new study also performed a direct head-to-head comparison of erythritol versus sugar.

“This research raises some concerns that a standard serving of an erythritol-sweetened food or beverage may acutely stimulate a direct prothrombotic effect,” says Dr. Tang, Research Director for Heart Failure and Cardiac Transplantation Medicine. “We feel strongly that erythritol and other sugar alcohols that are commonly used as sugar substitutes should be re-evaluated for potential long-term health effects, especially when such effects are not seen with sugar itself.”

Until more clinical studies are performed to further test the cardiovascular safety of these sugar alcohols when used as sugar substitutes, both Dr. Hazen and Dr. Tang are encouraging their high-risk patients to avoid highly processed “sugar-free” foods, instead recommending occasional sugar-sweetened treats.