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.

Stanley Hazen, MD, PhD, led the research team performing the studies published in Arteriosclerosis, Thrombosis and Vascular Biology. His lab conducted the precursor study in 2023 which first demonstrated that elevated blood erythritol levels are associated with an increased risk of cardiovascular events like heart attack or stroke. The new 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 new 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. Erythritol has become one of the most popular artificial sweeteners in the class that is known as sugar alcohols — typically used as a common replacement for table sugar in low-calorie, low-carbohydrate, “zero sugar” and “keto” products.

“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,” Dr. Hazen explains.

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.

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. This new study, 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.