{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:32:29Z","timestamp":1791066749006,"version":"4.1.0"},"reference-count":15,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,9]]},"abstract":"\n BACKGROUND:<\/jats:title>\n 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\u2013relevant 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.<\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930\u20137300] versus 3.75 [3.35\u20133.87] \u03bcmol\/L;\n P<\/jats:italic>\n <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 (\n P<\/jats:italic>\n <0.0001 for TRAP6 [thrombin activator peptide 6] and\n P<\/jats:italic>\n =0.004 for ADP) and the platelet \u03b1-granule marker CXCL4 (C-X-C motif ligand-4;\n P<\/jats:italic>\n <0.0001 for TRAP6 and\n P<\/jats:italic>\n =0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n REGISTRATION:<\/jats:title>\n \n URL:\n https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n ; Unique identifier: NCT04731363.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/atvbaha.124.321019","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T09:01:11Z","timestamp":1723107671000},"page":"2136-2141","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers\u2014Brief Report"],"prefix":"10.1161","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct04731363","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6952-5038","authenticated-orcid":true,"given":"Marco","family":"Witkowski","sequence":"first","affiliation":[{"name":"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.)"},{"name":"Now with Department of Cardiology, Angiology and Intensive Care, German Heart Center of Charit\u00e9, Campus Benjamin Franklin, Berlin, Germany (M.W.)."},{"name":"Friede Springer Cardiovascular Prevention Center at Charit\u00e9, Berlin, Germany and German Center for Cardiovascular Research (Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung; DZHK), Partner Site Berlin, Germany (M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6277-1079","authenticated-orcid":true,"given":"Jennifer","family":"Wilcox","sequence":"additional","affiliation":[{"name":"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.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valesha","family":"Province","sequence":"additional","affiliation":[{"name":"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.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6455-8228","authenticated-orcid":true,"given":"Zeneng","family":"Wang","sequence":"additional","affiliation":[{"name":"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.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0657-7121","authenticated-orcid":true,"given":"Ina","family":"Nemet","sequence":"additional","affiliation":[{"name":"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.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8335-735X","authenticated-orcid":true,"given":"W.H. Wilson","family":"Tang","sequence":"additional","affiliation":[{"name":"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.)"},{"name":"Heart, Vascular and Thoracic Institute (W.H.W.T., S.L.H.), Cleveland Clinic, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley L.","family":"Hazen","sequence":"additional","affiliation":[{"name":"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.)"},{"name":"Heart, Vascular and Thoracic Institute (W.H.W.T., S.L.H.), Cleveland Clinic, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.037401"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e31825c42ee"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02223-9"},{"key":"e_1_3_3_5_2","unstructured":"Food and Drug Administration. 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