Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Eur Heart J. 2024 Jul 12;45(27):2439-2452. doi: 10.1093/eurheartj/ehae244.
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.
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).
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.
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.
导致残余心血管疾病风险的途径和代谢物尚不清楚。低热量甜味剂是加工食品中广泛使用的糖替代品，具有预期的健康益处。许多低热量甜味剂是糖醇，它们也在内源性产生，尽管其水平比作为糖替代品摄入时低 1000 多倍。
对接受择期诊断性心脏评估的连续稳定受试者的过夜禁食血浆样本进行非靶向代谢组学研究；在独立的、无重叠的验证队列（n = 2149）中进行后续的稳定同位素稀释液相色谱串联质谱（LC-MS/MS）分析。互补的离体人血小板、富含血小板的血浆、全血和动物模型研究检查了木糖醇对体内血小板反应性和血栓形成的影响。最后，进行了一项干预研究，以评估木糖醇消耗对健康志愿者血小板功能的影响（n = 10）。
在最初的非靶向代谢组学研究（发现队列）中，一种暂定分配为木糖醇的多元醇的循环水平与（3 年）主要不良心血管事件（MACE）风险的发生有关。随后对木糖醇（而非其结构异构体）进行的稳定同位素稀释 LC-MS/MS 分析（验证队列）证实了其与发生 MACE 风险的相关性[第三与第一三分位调整后的危险比（95%置信区间），1.57（1.12-2.21），P <.01]。补充的机制研究表明，在空腹血浆中观察到的水平下，木糖醇增强了血小板反应性的多个指标，并增强了体内血栓形成。在干预研究中，饮用含木糖醇的饮料可显着提高血浆水平，并增强所有受试者的血小板反应性的多种功能测量。
木糖醇与发生 MACE 风险相关。此外，木糖醇既增强了体内血小板反应性又增强了血栓形成潜能。需要进一步研究木糖醇的心血管安全性。
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