Research News

Higher amounts of the sugar alcohol xylitol are associated with higher risk of cardiovascular events like heart attack and stroke, according to a new Cleveland Clinic study.

Xylitol is a zero-calorie sweetener about as sweet as sugar. It is used in sugar-free candy, low-sugar baked goods and oral products like toothpaste. A research team led by Stanley Hazen, MD, PhD, confirmed the association in large-scale patient analysis, preclinical research models and a clinical intervention study published in European Heart Journal.

The same research team found a similar link between erythritol and cardiovascular risk last year. Xylitol is not as prevalent as erythritol in keto or sugar-free food products in the U.S. but is common in other countries. The findings reinforce the need for further long-term studies on sugar alcohols, a current knowledge gap in public health even as more sugar-free products hit the market, says Dr. Hazen.

"This study again shows the immediate need for investigating sugar alcohols and artificial sweeteners, especially as they continue to be recommended in combatting conditions like obesity or diabetes," Dr. Hazen says. "It does not mean throw out your toothpaste if it has xylitol in it, but we should be aware that consumption of a product containing high levels could increase the risk of blood clot related events."

Dr. Hazen's team first identified that circulating xylitol levels were associated with a higher three-year risk of cardiovascular events in an analysis of over 3,000 patients in the U.S. and Europe. The third of patients with the highest amount of xylitol circulating in their plasma were more likely to experience a cardiovascular event.

Researchers then observed directly how xylitol may cause these effects in preclinical testing. They saw platelets were more likely to clot and cause thrombosis after introducing xylitol. The research team also conducted a human intervention study. Researchers tracked platelet activity from people who ingested a xylitol-sweetened drink versus a glucose-sweetened drink. Every measure of clotting ability significantly increased immediately following ingestion, Dr. Hazen says.

Dr. Hazen directs Cleveland Clinic's Center for Microbiome & Human Health. The xylitol study is a prime example of his team's approach to identifying risk factors to cardiovascular health outside of traditional measures like high blood pressure or cholesterol. The team also developed a test that other teams can use to confirm circulating xylitol levels, which will be critical to future investigations.

"We need to be comprehensive in our approach to evaluating common components in our diet, including sugar alcohols and artificial sweeteners," says Dr. Hazen. "It's only through extended research that we can develop sound labeling guidelines and provide the best nutritional recommendations for these products."

Dr. Hazen also serves as the chair of the Department of Cardiovascular & Metabolic Sciences and co-section head of Preventive Cardiology. He holds the Jan Bleeksma Chair in Vascular Cell Biology and Atherosclerosis. Dr. Marco Witkowski, a cardiologist from The Berlin Charité Hospital, was the first author of the manuscript and performed the studies as part of his PhD thesis research while working in Dr Hazen's laboratory at the Cleveland Clinic.

Other investigators who contributed to the paper include Ina Nemet, PhD, CVMS Assistant Staff, and W.H. Wilson Tang, MD, CVMS staff and a clinician-scientist.