Elevated levels of xylitol in the blood were linked to a heightened risk of severe cardiovascular events, according to new research.
A study led by Stanley Hazen, MD, at Cleveland Clinic associated the sugar substitute xylitol with an increased risk of cardiovascular events, such as myocardial infarction and stroke. Published in the European Heart Journal, the study analyzed data from over 3,000 patients in the U.S. and Europe.
Xylitol, a sugar alcohol found in sugar-free products like candy and toothpaste, was often marketed as a healthier alternative to sugar. The study revealed that elevated xylitol levels correlated with a higher incidence of major adverse cardiovascular events over three years, with a statistically significant adjusted hazard ratio of 1.57 (95% CI, 1.12–2.21; P < .01).
The researchers used untargeted metabolomics and stable isotope dilution LC-MS/MS to validate their findings. In vitro studies demonstrated xylitol's enhancement of platelet reactivity and thrombosis potential. An intervention study with 10 healthy volunteers showed significant increases in platelet function markers after xylitol ingestion.
“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,” said Dr. Hazen in a statement. The authors emphasized the need for additional research to evaluate the long-term cardiovascular safety of xylitol.
The initial untargeted metabolomics study involved 1,157 patients undergoing elective diagnostic cardiac evaluations. This was followed by a validation cohort study using stable isotope dilution LC-MS/MS analyses on 2,149 patients. Both studies confirmed the association of elevated xylitol levels with increased cardiovascular event risk. The interventional study highlighted that xylitol consumption led to significant increases in multiple functional measures of platelet responsiveness in healthy volunteers.
Preclinical research further corroborated these findings. Human platelet and animal model studies showed that xylitol enhanced platelet reactivity and thrombosis formation at levels observed in fasting plasma. Researchers noted that these effects were not seen with glucose ingestion, suggesting a unique risk profile for xylitol.
Dr. Hazen's team had previously identified similar risks associated with other sugar alcohols like erythritol. This underscored the urgency of re-evaluating the cardiovascular safety of these widely used sugar substitutes, particularly as their consumption continued to rise globally.
“This study again showed the immediate need for investigating sugar alcohols and artificial sweeteners, especially as they continue to be recommended in combating conditions like obesity or diabetes,” said Dr. Hazen.
The authors acknowledged that while clinical observational studies could demonstrate association rather than causation, the consistent findings across multiple study designs strongly suggested a link between xylitol and cardiovascular risk. They recommended consulting healthcare providers for personalized dietary advice and emphasized the need for further research to fully understand the long-term implications.
Dr. Hazen's ongoing research aimed to identify chemical signatures in the blood that could predict future cardiovascular and metabolic diseases, continuing his pioneering work in atherosclerosis and inflammatory disease research.
Full disclosures could be found in the study.