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Xylitol Is Prothrombotic and Associated With CV Risk
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND AND AIMS
The pathways and metabolites that contribute to residual cardiovascular disease risks are unclear. Low-calorie sweeteners are widely used sugar substitutes in processed foods with presumed health benefits. Many low-calorie sweeteners are sugar alcohols that also are produced endogenously, albeit at levels over 1000-fold lower than observed following consumption as a sugar substitute.
METHODS
Untargeted metabolomics studies were performed on overnight fasting plasma samples in a discovery cohort (n = 1157) of sequential stable subjects undergoing elective diagnostic cardiac evaluations; subsequent stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses were performed on an independent, non-overlapping validation cohort (n = 2149). Complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies examined the effect of xylitol on platelet responsiveness and thrombus formation in vivo. Finally, an intervention study was performed to assess the effects of xylitol consumption on platelet function in healthy volunteers (n = 10).
RESULTS
In initial untargeted metabolomics studies (discovery cohort), circulating levels of a polyol tentatively assigned as xylitol were associated with incident (3-year) major adverse cardiovascular event (MACE) risk. Subsequent stable isotope dilution LC-MS/MS analyses (validation cohort) specific for xylitol (and not its structural isomers) confirmed its association with incident MACE risk [third vs. first tertile adjusted hazard ratio (95% confidence interval), 1.57 (1.12–2.21), P < .01]. Complementary mechanistic studies showed xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma. In interventional studies, consumption of a xylitol-sweetened drink markedly raised plasma levels and enhanced multiple functional measures of platelet responsiveness in all subjects.
CONCLUSIONS
Xylitol is associated with incident MACE risk. Moreover, xylitol both enhanced platelet reactivity and thrombosis potential in vivo. Further studies examining the cardiovascular safety of xylitol are warranted.
Additional Info
Disclosure statements are available on the authors' profiles:
Xylitol is prothrombotic and associated with cardiovascular risk
Eur Heart J 2024 Jun 06;[EPub Ahead of Print], M Witkowski, I Nemet, XS Li, J Wilcox, M Ferrell, H Alamri, N Gupta, Z Wang, WHW Tang, SL HazenFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Xylitol and Thrombotic Risk
Polyol sugars that end in “ol” are in many processed foods and drinks. They are also the last “P” in the FODMAP diet and should be avoided in individuals with irritable bowel syndrome due to their risk of causing abdominal pain. There is now growing evidence that polyol sugars (eg, erythritol and xylitol) also increase the risk of platelet aggregation and thrombosis.
PracticeUpdate reviewed a study on another artificial sweetener, erythritol, by this research group. This paper used a similar model and compared the incidence of major adverse cardiovascular events (MACE) in individuals with high versus low levels over a period of 3 years among those presenting for cardiovascular diagnostic procedures (N = 1157). Individuals in the highest tertile of serum xylitol experienced higher rates of MACE. This was also true for erythritol. They also showed increased platelet aggregation and thrombosis in mice and human models after intentional ingestion (see graphic below comparing xylitol and erythritol levels and the risk of MACE over a period of 3 years).
These polyol sugars are used in processed foods, ketogenic foods, and foods marketed to diabetics to reduce the number of calories and sugar content. This research shows that the amounts of polyol sweeteners found in daily food intake can increase thrombotic risk, compounding the risk already present in this high-risk population.