Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute (M.W., J.W., V.P., Z.W., I.N., W.H.W.T., S.L.H.).
Now with Department of Cardiology, Angiology and Intensive Care, German Heart Center of Charité, Campus Benjamin Franklin, Berlin, Germany (M.W.).
Arterioscler Thromb Vasc Biol. 2024 Sep;44(9):2136-2141. doi: 10.1161/ATVBAHA.124.321019. Epub 2024 Aug 8.
Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models. Effects of dietary erythritol on thrombosis phenotypes in humans have not been examined.
Using a prospective interventional study design, we tested the impact of erythritol or glucose consumption on multiple indices of stimulus-dependent platelet responsiveness in healthy volunteers (n=10 per group). Erythritol plasma levels were quantified with liquid chromatography tandem mass spectrometry. Platelet function at baseline and following erythritol or glucose ingestion was assessed via both aggregometry and analysis of granule markers released.
Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930-7300] versus 3.75 [3.35-3.87] μmol/L; <0.0001) and exhibited acute enhancement of stimulus-dependent aggregation responses in all subjects, agonists, and doses examined. Erythritol ingestion also enhanced stimulus-dependent release of the platelet dense granule marker serotonin (<0.0001 for TRAP6 [thrombin activator peptide 6] and =0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4; <0.0001 for TRAP6 and =0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4.
Ingestion of a typical quantity of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity in healthy volunteers, raising concerns that erythritol consumption may enhance thrombosis potential. Combined with recent large-scale clinical observational studies and mechanistic cell-based and animal model studies, the present findings suggest that discussion of whether erythritol should be reevaluated as a food additive with the Generally Recognized as Safe designation is warranted.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04731363.
尽管人工和非营养性甜味剂被美国和欧盟监管机构广泛使用并普遍认为是安全的，但目前还没有临床试验来评估它们对长期心血管疾病风险或短期与心血管疾病相关表型的影响。最近的研究报告称，常用甜味剂赤藓糖醇的空腹血浆水平与心血管疾病风险升高有关，并在体外和动物模型中增强血栓形成潜力。尚未研究饮食赤藓糖醇对人类血栓形成表型的影响。
我们使用前瞻性干预性研究设计，测试了赤藓糖醇或葡萄糖消耗对健康志愿者血小板反应性多个刺激依赖性指标的影响（每组 10 人）。使用液相色谱串联质谱法定量测定赤藓糖醇的血浆水平。通过聚集分析和分析释放的颗粒标志物评估基线时以及摄入赤藓糖醇或葡萄糖后的血小板功能。
饮食赤藓糖醇（30 克）而非葡萄糖（30 克）可使赤藓糖醇的血浆浓度增加 1000 多倍（6480 [5930-7300] 与 3.75 [3.35-3.87] μmol/L；<0.0001），并使所有受试者、激动剂和剂量的刺激依赖性聚集反应均增强。赤藓糖醇摄入还增强了刺激依赖性释放血小板致密颗粒标志物 5-羟色胺（TRAP6 [凝血酶激活肽 6] <0.0001 和 ADP =0.004）和血小板α-颗粒标志物 CXCL4（C-X-C 基序配体-4；TRAP6 <0.0001 和 ADP =0.06）。相比之下，葡萄糖摄入不会引起 5-羟色胺或 CXCL4 刺激依赖性释放的显著增加。
摄入典型数量的非营养性甜味剂赤藓糖醇而非葡萄糖可增强健康志愿者的血小板反应性，这引发了人们的担忧，即赤藓糖醇的摄入可能会增加血栓形成的潜力。结合最近的大规模临床观察研究和基于细胞的机制研究和动物模型研究，本研究结果表明，应该重新考虑是否应将赤藓糖醇重新评估为具有“一般公认安全”地位的食品添加剂。
