In the metabolomic cohorts, comparing the highest to lowest tertile, plasma levels of xylitol were associated with a 57% higher 3-year risk for incident MACE (major adverse cardiovascular events such as heart attack or stroke). In the animal (in vivo) model, xylitol levels (equivalent to fasting levels in the highest tertile) were associated with unfavorable effects on multiple indices of platelet reactivity and thrombosis formation, and in the sample of 10 volunteers, consuming a xylitol-sweetened drink increased multiple measures of platelet reactivity.
Thus, although this was not a controlled trial and cannot show causality between xylitol and cardiovascular events, the mechanistic data amplifies the concern suggested by the observational data. There are other plausible explanations for the risk observed from the cohort data. For example, people at higher cardiovascular risk may be attempting to reduce their sugar consumption and replace it with xylitol as a perceived healthier choice. Yet their baseline risk factors may predispose them to higher risk for MACE, independently of xylitol consumption. Additionally, supplemental xylitol may carry risks unique from the small amounts found in foods. However, the very limited evidence that xylitol directly increases platelet activity, combined with the observed increase in MACE incidence, warrants concern and further study.