A Cleveland Clinic study has linked Xylitol, a common zero-calorie sweetener found in sugar-free candy and toothpaste, to an increased risk of cardiovascular events like heart attack and stroke.

The team, led by Stanley Hazen, confirmed the association in a large-scale patient analysis, preclinical research models and a clinical intervention study. The findings were published in the European Heart Journal.

Xylitol is a common sugar substitute used in sugar-free candy, gums, baked goods and oral products like toothpaste. Over the past decade, the use of sugar substitutes, including sugar alcohols and artificial sweeteners, has increased significantly in processed foods that are promoted as healthy alternatives.

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.

Stanley, chair of cardiovascular and metabolic sciences at Cleveland Clinic’s Lerner Research Institute and co-section head of preventive cardiology in the Heart, Vascular and Thoracic Institute, said, “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. 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.”

The results

In the study, researchers identified that high levels of circulating xylitol were associated with an elevated three-year risk of cardiovascular events in an analysis of more than 3,000 patients in the U.S. and Europe.

A third of patients with the highest amount of xylitol in their plasma were more likely to experience a cardiovascular event. To confirm the findings, the research team conducted pre-clinical testing and found that xylitol caused platelets to clot and heightened the risk of thrombosis. Researchers also tracked platelet activity from people who ingested a xylitol-sweetened drink versus a glucose-sweetened drink and found that every measure of clotting ability significantly increased immediately following ingestion of xylitol but not glucose.

Plans for further research

The authors note that further studies assessing the long-term cardiovascular safety of xylitol are warranted. The research has several limitations, including that clinical observation studies demonstrate association, not causation.

The research is part of Stanley’s ongoing investigation into factors contributing to residual cardiovascular risk.

His team follows patients over time and finds chemical signatures in blood that can predict the future development of heart and metabolic disease. He has made pioneering discoveries in atherosclerosis and inflammatory disease research, including the seminal discovery linking gut microbial pathways to cardiovascular disease and metabolic diseases.

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