Xylitol is prothrombotic and associated with cardiovascular risk.
Level 3 - non-randomized controlled study
Prospective observational cohort studies with mechanistic assays and small human interventional validation
PubMed 38842092 · doi:10.1093/eurheartj/ehae244
What was done
Untargeted metabolomics on overnight fasting plasma was conducted in a discovery cohort of stable patients undergoing elective diagnostic cardiac evaluations (n = 1157). Findings were evaluated in an independent validation cohort using stable isotope dilution LC-MS/MS (n = 2149) to assess incident 3-year major adverse cardiovascular events (MACE). Complementary mechanistic assays were performed in isolated human platelets, platelet-rich plasma, whole blood, and animal models. An intervention study evaluated the acute effects of xylitol consumption on platelet responsiveness in healthy volunteers (n = 10).
What was found
In the validation cohort, circulating xylitol was significantly associated with incident 3-year MACE risk (third vs. first tertile adjusted hazard ratio: 1.57, 95% CI: 1.12–2.21, P < .01). Mechanistic studies demonstrated that xylitol enhanced platelet reactivity and in vivo thrombosis at concentrations detected in fasting plasma. In the interventional study (n = 10), ingestion of a xylitol-sweetened drink increased plasma xylitol concentrations and enhanced functional measures of platelet responsiveness in all subjects.
Why it matters
This study links the common sugar substitute xylitol to increased incident cardiovascular risk and prothrombotic platelet activation. These findings challenge the assumed cardiovascular safety of sugar alcohols widely used in processed foods.
Limits
The clinical cohorts consisted of individuals undergoing elective cardiac evaluations, potentially limiting generalizability to the general healthy population. The observational analyses could not differentiate endogenous xylitol production from dietary intake. The human feeding intervention was very small (n = 10) and only evaluated acute surrogate platelet markers rather than long-term clinical events.
Cited by
- contradicts The study linking xylitol to heart risks evaluated a 30-gram bolus dose in older, fasting cardiac patients and demonstrated increased platelet aggregation rather than actual heart attacks.