{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:28:05Z","timestamp":1790947685640,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:00:00Z","timestamp":1726272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services","award":["W81XWH-18-1-0275"],"award-info":[{"award-number":["W81XWH-18-1-0275"]}]},{"name":"Intramural Research Program of the National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services","award":["W81XWH-12-1-0369"],"award-info":[{"award-number":["W81XWH-12-1-0369"]}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-18-1-0275"],"award-info":[{"award-number":["W81XWH-18-1-0275"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-12-1-0369"],"award-info":[{"award-number":["W81XWH-12-1-0369"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.S. Army Medical Research Acquisition Activity through the Peer Review Cancer Research Program Discovery Award","award":["W81XWH-18-1-0275"],"award-info":[{"award-number":["W81XWH-18-1-0275"]}]},{"name":"U.S. Army Medical Research Acquisition Activity through the Peer Review Cancer Research Program Discovery Award","award":["W81XWH-12-1-0369"],"award-info":[{"award-number":["W81XWH-12-1-0369"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Erythritol occurs naturally in some fruits and fermented foods, and has also been used as an artificial sweetener since the 1990s. Although there have been questions and some studies regarding its potential adverse health effects, the association between serum erythritol and long-term mortality has not been evaluated. To examine the association between serum erythritol\u2019s biochemical status and risk of overall and cause-specific mortality, a prospective cohort analysis was conducted using participants in the ATBC Study (1985\u20131993) previously selected for metabolomic sub-studies. The analysis included 4468 participants, among whom 3377 deaths occurred during an average of 19.1 years of follow-up. Serum erythritol was assayed using an untargeted, global, high-resolution, accurate-mass platform of ultra-high-performance liquid and gas chromatography. Cause-specific deaths were identified through Statistics Finland and defined by the International Classification of Diseases. After adjustment for potential confounders, serum erythritol was associated with increased risk of overall mortality (HR = 1.50 [95% CI = 1.17\u20131.92]). We found a positive association between serum erythritol and cardiovascular disease mortality risk (HR = 1.86 [95% CI = 1.18\u20132.94]), which was stronger for heart disease mortality than for stroke mortality risk (HR = 3.03 [95% CI = 1.00\u20139.17] and HR = 2.06 [95% CI = 0.72\u20135.90], respectively). Cancer mortality risk was also positively associated with erythritol (HR = 1.54 [95% CI = 1.09\u20132.19]). The serum erythritol\u2013overall mortality risk association was stronger in men \u2265 55 years of age and those with diastolic blood pressure \u2265 88 mm Hg (p for interactions 0.045 and 0.01, respectively). Our study suggests that elevated serum erythritol is associated with increased risk of overall, cardiovascular disease, and cancer mortality. Additional studies clarifying the role of endogenous production and dietary\/beverage intake of erythritol in human health and mortality are warranted.<\/jats:p>","DOI":"10.3390\/nu16183099","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T10:56:57Z","timestamp":1726484217000},"page":"3099","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Serum Erythritol and Risk of Overall and Cause-Specific Mortality in a Cohort of Men"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1671-3131","authenticated-orcid":false,"given":"Jungeun","family":"Lim","sequence":"first","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"},{"name":"Epidemiology and Community Health Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyokyoung G.","family":"Hong","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7808-9477","authenticated-orcid":false,"given":"Jiaqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"},{"name":"National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Stolzenberg-Solomon","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison M.","family":"Mondul","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA"},{"name":"Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie J.","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetrius","family":"Albanes","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,14]]},"reference":[{"key":"ref_1","unstructured":"Marie, S., and Piggott, J.R. Sugar alcohols. Handbook of Sweeteners, Springer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s00253-017-8654-1","article-title":"Erythritol as sweetener-wherefrom and whereto?","volume":"102","author":"Regnat","year":"2018","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Food Additives and Flavourings (FAF), Younes, M., Aquilina, G., Castle, L., Degen, G., Engel, K.-H., Fowler, P.J., Fernandez, M.J.F., F\u00fcrst, P., and Gundert-Remy, U. (2023). Re-evaluation of erythritol (E\u2009968) as a food additive. EFSA J., 21, e8430.","DOI":"10.2903\/j.efsa.2023.8430"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.physbeh.2016.02.039","article-title":"The safety and regulatory process for low calorie sweeteners in the United States","volume":"164","author":"Roberts","year":"2016","journal-title":"Physiol. Behav."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1080\/17482970600982719","article-title":"Sweeteners permitted in the European Union: Safety aspects","volume":"50","author":"Mortensen","year":"2006","journal-title":"Scand. J. Food Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1111\/ijcp.12703","article-title":"Systematic review of the relationship between artificial sweetener consumption and cancer in humans: Analysis of 599,741 participants","volume":"69","author":"Mishra","year":"2015","journal-title":"Int. J. Clin. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e071204","DOI":"10.1136\/bmj-2022-071204","article-title":"Artificial sweeteners and risk of cardiovascular diseases: Results from the prospective NutriNet-Sant\u00e9 cohort","volume":"378","author":"Debras","year":"2022","journal-title":"BMJ"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Debras, C., Chazelas, E., Srour, B., Druesne-Pecollo, N., Esseddik, Y., de Edelenyi, F.S., Aga\u00ebsse, C., De Sa, A., Lutchia, R., and Gigandet, S. (2022). Artificial sweeteners and cancer risk: Results from the NutriNet-Sant\u00e9 population-based cohort study. PLoS Med., 19.","DOI":"10.1371\/journal.pmed.1003950"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1159\/000458769","article-title":"Chronic Consumption of Artificial Sweetener in Packets or Tablets and Type 2 Diabetes Risk: Evidence from the E3N-European Prospective Investigation into Cancer and Nutrition Study","volume":"70","author":"Fagherazzi","year":"2017","journal-title":"Ann. Nutr. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1161\/ATVBAHA.124.321019","article-title":"Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers","volume":"44","author":"Witkowski","year":"2024","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/s41591-023-02223-9","article-title":"The artificial sweetener erythritol and cardiovascular event risk","volume":"29","author":"Witkowski","year":"2023","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s42255-022-00711-9","article-title":"Cytosolic aldose metabolism contributes to progression from cirrhosis to hepatocarcinogenesis","volume":"5","author":"Oaks","year":"2023","journal-title":"Nat. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"The ATBC Cancer Prevention Study Group (1994). The alpha-tocopherol, beta-carotene lung cancer prevention study: Design, methods, participant characteristics, and compliance. Ann. Epidemiol., 4, 1\u201310.","DOI":"10.1016\/1047-2797(94)90036-1"},{"key":"ref_14","first-page":"245","article-title":"Multicentre study of a new enzymatic method of cholesterol determination","volume":"22","author":"Kattermann","year":"1984","journal-title":"J. Clin. Chem. Clin. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1093\/clinchem\/32.5.874","article-title":"Retinal, alpha-tocopherol, lycopene, and alpha and beta-carotene simultaneously determined in plasma by isocratic liquid chromatography","volume":"32","author":"Milne","year":"1986","journal-title":"Clin. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"488","DOI":"10.3945\/ajcn.113.062778","article-title":"Metabolomic profile of response to supplementation with \u03b2-carotene in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study","volume":"98","author":"Mondul","year":"2013","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6158436","DOI":"10.1155\/2016\/6158436","article-title":"Serum metabolomic response to long-term supplementation with all-rac-alpha-tocopheryl acetate in a randomized controlled trial","volume":"2016","author":"Mondul","year":"2016","journal-title":"J. Nutr. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1158\/1055-9965.EPI-20-0187","article-title":"Serum Metabolomic Response to Low- and High-Dose Vitamin E Supplementation in Two Randomized Controlled Trials","volume":"29","author":"Huang","year":"2020","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1007\/s11306-014-0643-0","article-title":"1-stearoylglycerol is associated with risk of prostate cancer: Results from serum metabolomic profiling","volume":"10","author":"Mondul","year":"2014","journal-title":"Metabolomics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1002\/ijc.29576","article-title":"Metabolomic analysis of prostate cancer risk in a prospective cohort: The alpha-tocolpherol, beta-carotene cancer prevention (ATBC) study","volume":"137","author":"Mondul","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1002\/ijc.32218","article-title":"Prospective serum metabolomic profiling of lethal prostate cancer","volume":"145","author":"Huang","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Huang, J., Zhao, B., Weinstein, S.J., Albanes, D., and Mondul, A.M. (2022). Metabolomic profile of prostate cancer-specific survival among 1812 Finnish men. BMC Med., 20.","DOI":"10.1186\/s12916-022-02561-4"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1136\/gutjnl-2019-319811","article-title":"Associations between metabolites and pancreatic cancer risk in a large prospective epidemiological study","volume":"69","author":"Derkach","year":"2020","journal-title":"Gut"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"70366","DOI":"10.18632\/oncotarget.19705","article-title":"A prospective study of serum metabolites and glioma risk","volume":"8","author":"Huang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lim, J.E., Huang, J., Weinstein, S.J., Parisi, D., M\u00e4nnist\u00f6, S., and Albanes, D. (2023). Serum metabolomic profile of hair dye use. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-30590-3"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6656","DOI":"10.1021\/ac901536h","article-title":"Integrated, nontargeted ultrahigh performance liquid chromatography\/electrospray ionization tandem mass spectrometry platform for the identification and relative quantification of the small-molecule complement of biological systems","volume":"81","author":"Evans","year":"2009","journal-title":"Anal. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S264","DOI":"10.1006\/rtph.1996.0108","article-title":"Chronic toxicity and carcinogenicity study of erythritol in rats","volume":"24","author":"Lina","year":"1996","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_28","first-page":"513","article-title":"Effects of erythritol on endothelial function in patients with type 2 diabetes mellitus: A pilot study","volume":"51","author":"Flint","year":"2014","journal-title":"Acta Diabetol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"k4718","DOI":"10.1136\/bmj.k4718","article-title":"Association between intake of non-sugar sweeteners and health outcomes: Systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies","volume":"364","author":"Toews","year":"2019","journal-title":"BMJ"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1093\/advances\/nmaa110","article-title":"Association of Consumption of Sugar-Sweetened Beverages or Artificially Sweetened Beverages with Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies","volume":"12","author":"Zhang","year":"2021","journal-title":"Adv. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Mazi, T.A., and Stanhope, K.L. (2023). Elevated Erythritol: A Marker of Metabolic Dysregulation or Contributor to the Pathogenesis of Cardiometabolic Disease?. Nutrients, 15.","DOI":"10.3390\/nu15184011"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E4233","DOI":"10.1073\/pnas.1620079114","article-title":"Erythritol is a pentose-phosphate pathway metabolite and associated with adiposity gain in young adults","volume":"114","author":"Hootman","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16095","DOI":"10.1074\/jbc.RA119.009049","article-title":"Unexpected roles for ADH1 and SORD in catalyzing the final step of erythritol biosynthesis","volume":"294","author":"Schlicker","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bordier, V., Teysseire, F., Senner, F., Schlotterbeck, G., Drewe, J., Beglinger, C., W\u00f6lnerhanssen, B.K., and Meyer-Gerspach, A.C. (2022). Absorption and Metabolism of the Natural Sweeteners Erythritol and Xylitol in Humans: A Dose-Ranging Study. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179867"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"van Gerwen, M., Colicino, E., Guan, H., Dolios, G., Nadkarni, G.N., Vermeulen, R.C.H., Wolff, M.S., Arora, M., Genden, E.M., and Petrick, L.M. (2023). Per- and polyfluoroalkyl substances (PFAS) exposure and thyroid cancer risk. EBioMedicine, 97.","DOI":"10.1016\/j.ebiom.2023.104831"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lee-Sarwar, K.A., Fischer-Rasmussen, K., B\u00f8nnelykke, K., Bisgaard, H., Chawes, B., Kelly, R.S., Lasky-Su, J., Zeiger, R.S., O\u2019connor, G.T., and Bacharier, L.B. (2023). Omega-3 Fatty Acids Interact with DPP10 Region Genotype in Association with Childhood Atopy. Nutrients, 15.","DOI":"10.3390\/nu15102416"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1093\/ajcn\/nqaa430","article-title":"Circulating trimethylamine N-oxide in association with diet and cardiometabolic biomarkers: An international pooled analysis","volume":"113","author":"Yang","year":"2021","journal-title":"Am. J. Clin. Nutr."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/18\/3099\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:56:06Z","timestamp":1760111766000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/18\/3099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,14]]},"references-count":37,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["nu16183099"],"URL":"https:\/\/doi.org\/10.3390\/nu16183099","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,14]]}}}