Sugar Substitute Raises Risk of Major Adverse Cardiovascular Events: Daily Dose

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On June 12, 2024, we reported on findings from a study published in the European Heart Journal that examined the potential link between sugar alcohol xylitol and residual cardiovascular disease risks.

The study

The researchers performed 3 distinct clinical studies with nonoverlapping human participants (n = 1157) and a validation cohort (n = 2149). Blood samples from healthy volunteers were collected for platelet-related studies, including aggregometry studies in platelet-rich plasma, intracellular calcium measurements, platelet flow cytometry assay, imaging flow cytometry in whole blood, whole-blood in vitro thrombosis assay, carotid artery FeCI3 injury model, and untargeted and targeted mass spectrometry analysis of human plasma.

At baseline, participants in the discovery cohort had a median (IQR) age of 65 (56-72) years, 64% were male, and median (IQR) body mass index was 28.4 (25.4-32.1) kg/m². Additionally, 22% of participants in this cohort had diabetes, 72% had hypertension, and 14% were current smokers.

The findings

In the discovery cohort, circulating levels of a polyol tentatively assigned as xylitol were associated with incident (3-year) MACE risk. In the validation cohort, subsequent mass spectrometry analysis specific for xylitol confirmed the association of incident MACE risk, finding that a third of participants with the highest amount of xylitol in their plasma were more likely to experience a cardiovascular event (third vs first tertile adjusted HR, 1.57; 95% CI, 1.12-2.21; P < .01).

Furthermore, the researchers conducted preclinical testing to confirm these findings. Complementary mechanistic studies showed xylitol enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma. Moreover, when tracking platelet activity after consumption of a xylitol-based sweetened drink, the researchers identified raised plasma levels and enhanced measures of platelet responsiveness in all subjects.

Authors' comment

“Our studies suggest that xylitol will likely confer heightened thrombosis potential in the same vulnerable participants that it is marketed towards and intended to protect."

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