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Xylitol Linked to Incident Major Adverse Cardiovascular Event Risk

Xylitol linked to incident MACE risk in initial untargeted metabolomics study and confirmed in validation cohort

By Elana Gotkine HealthDay Reporter

MONDAY, June 17, 2024 (HealthDay News) — Xylitol is associated with incident major adverse cardiovascular event (MACE) risk, according to a study published online June 6 in the European Heart Journal.

Marco Witkowski, M.D., from the Lerner Research Institute at the Cleveland Clinic, and colleagues performed untargeted metabolomics studies on overnight fasting plasma samples in a discovery cohort of 1,157 sequential stable patients undergoing elective diagnostic cardiac evaluations. Subsequent isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses were performed on an independent validation cohort comprising 2,149 participants. The effect of xylitol on platelet responsiveness and thrombus formation in vivo was examined in complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies. Finally, the effects of xylitol consumption were examined on platelet function in 10 healthy volunteers.

The researchers found that circulating levels of a polyol tentatively assigned as xylitol were associated with incident MACE risk in the initial untargeted metabolomics study (discovery cohort). The association of xylitol with incident MACE risk was confirmed in stable isotope dilution LC-MS/MS analyses (third versus first tertile adjusted hazard ratio, 1.57). Xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma were seen in complementary mechanistic studies. Xylitol-sweetened drinks markedly raised plasma levels in interventional studies, and enhanced multiple functional measures of platelet responsiveness in all individuals.

“Our studies suggest that xylitol will likely confer heightened thrombosis potential in the same vulnerable patients that it is marketed towards and intended to protect,” the authors write.

Several authors disclosed ties to the biopharmaceutical industry; several authors are named coinventors on pending and issued patents relating to cardiovascular diagnostics and therapeutics.

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