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The artificial sweetener erythritol and cardiovascular event risk
M. Witkowski, I. Nemet, H. Alamri, J. Wilcox, N. Gupta, N. Nimer, A. Haghikia, XS. Li, Y. Wu, PP. Saha, I. Demuth, M. König, E. Steinhagen-Thiessen, T. Cajka, O. Fiehn, U. Landmesser, WHW. Tang, SL. Hazen
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
P01 HL147823
NHLBI NIH HHS - United States
R01 HL103866
NHLBI NIH HHS - United States
Health & Medicine (ProQuest) od 2000-01-01 do Před 1 rokem
Odkazy
PubMed
36849732
DOI
10.1038/s41591-023-02223-9
Knihovny.cz E-zdroje
- MeSH
- erythritol farmakologie MeSH
- infarkt myokardu * MeSH
- lidé MeSH
- prospektivní studie MeSH
- sladidla * škodlivé účinky MeSH
- srdce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Artificial sweeteners are widely used sugar substitutes, but little is known about their long-term effects on cardiometabolic disease risks. Here we examined the commonly used sugar substitute erythritol and atherothrombotic disease risk. In initial untargeted metabolomics studies in patients undergoing cardiac risk assessment (n = 1,157; discovery cohort, NCT00590200 ), circulating levels of multiple polyol sweeteners, especially erythritol, were associated with incident (3 year) risk for major adverse cardiovascular events (MACE; includes death or nonfatal myocardial infarction or stroke). Subsequent targeted metabolomics analyses in independent US (n = 2,149, NCT00590200 ) and European (n = 833, DRKS00020915 ) validation cohorts of stable patients undergoing elective cardiac evaluation confirmed this association (fourth versus first quartile adjusted hazard ratio (95% confidence interval), 1.80 (1.18-2.77) and 2.21 (1.20-4.07), respectively). At physiological levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo. Finally, in a prospective pilot intervention study ( NCT04731363 ), erythritol ingestion in healthy volunteers (n = 8) induced marked and sustained (>2 d) increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity and thrombosis potential in in vitro and in vivo studies. Our findings reveal that erythritol is both associated with incident MACE risk and fosters enhanced thrombosis. Studies assessing the long-term safety of erythritol are warranted.
Berlin Institute of Health Berlin Germany
Berlin Institute of Health Center for Regenerative Therapies Berlin Germany
Department of Endocrinology and Metabolism Charité Universitätsmedizin Berlin Berlin Germany
Department of Mathematics and Statistics Cleveland State University Cleveland OH USA
Friede Springer Cardiovascular Prevention Center at Charité Berlin Germany
German Center for Cardiovascular Research Partner Site Berlin Berlin Germany
Heart Vascular and Thoracic Institute Cleveland Clinic Cleveland OH USA
Institute of Physiology of the Czech Academy of Sciences Prague Czech Republic
West Coast Metabolomics Center University of California Davis CA USA
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- $a Artificial sweeteners are widely used sugar substitutes, but little is known about their long-term effects on cardiometabolic disease risks. Here we examined the commonly used sugar substitute erythritol and atherothrombotic disease risk. In initial untargeted metabolomics studies in patients undergoing cardiac risk assessment (n = 1,157; discovery cohort, NCT00590200 ), circulating levels of multiple polyol sweeteners, especially erythritol, were associated with incident (3 year) risk for major adverse cardiovascular events (MACE; includes death or nonfatal myocardial infarction or stroke). Subsequent targeted metabolomics analyses in independent US (n = 2,149, NCT00590200 ) and European (n = 833, DRKS00020915 ) validation cohorts of stable patients undergoing elective cardiac evaluation confirmed this association (fourth versus first quartile adjusted hazard ratio (95% confidence interval), 1.80 (1.18-2.77) and 2.21 (1.20-4.07), respectively). At physiological levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo. Finally, in a prospective pilot intervention study ( NCT04731363 ), erythritol ingestion in healthy volunteers (n = 8) induced marked and sustained (>2 d) increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity and thrombosis potential in in vitro and in vivo studies. Our findings reveal that erythritol is both associated with incident MACE risk and fosters enhanced thrombosis. Studies assessing the long-term safety of erythritol are warranted.
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