{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T03:48:58Z","timestamp":1762660138211,"version":"build-2065373602"},"reference-count":26,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008173","name":"Intermountain Research and Medical Foundation","doi-asserted-by":"publisher","award":["759","Dell Loy Hansen Heart Foundation"],"award-info":[{"award-number":["759","Dell Loy Hansen Heart Foundation"]}],"id":[{"id":"10.13039\/100008173","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Red cell distribution width (RDW) predicts cardiovascular outcomes, but it is unstudied with regard to intermittent fasting. In WONDERFUL trial subjects, the effect of the interaction between baseline RDW and intermittent fasting on changes in insulin and other cardiometabolic endpoints and the effect of fasting on changes in RDW were evaluated. The subjects enrolled were aged 21\u201370 years and were free of statins, anti-diabetes medications, and chronic diseases, and had \u22651 metabolic syndrome feature, as well as elevated low-density lipoprotein cholesterol. Subjects were randomized to 24-h, water-only fasting (twice per week for 4 weeks, once per week for 22 weeks) or 26 weeks of ad libitum eating. Subjects (N = 71; n = 38 intermittent fasting, n = 33 controls) had more substantial changes in insulin in intermittent fasting vs. controls (\u22123.45 \u00b1 2.27 vs. 0.48 \u00b1 3.55 mIU\/L) when baseline RDW size distribution (RDW-SD) was \u2265median (42.6 fL) than &lt;median (\u22121.99 \u00b1 2.80 vs. \u22121.08 \u00b1 3.40 mIU\/L) (p-interaction = 0.039). Results were similar but weaker for glucose, HOMA-IR, and metabolic syndrome score. RDW-SD (intermittent fasting: 1.27 \u00b1 9.6 fL vs. control: \u22120.37 \u00b1 1.76 fL, p = 0.34) was unchanged by fasting at 26 weeks. Intermittent fasting decreased insulin more in subjects with higher baseline RDW. RDW may identify individuals who derive the most health benefits from intermittent fasting and who have the most cause to adhere to a fasting regimen.<\/jats:p>","DOI":"10.3390\/nu13124407","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T21:46:58Z","timestamp":1639086418000},"page":"4407","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Preferential Metabolic Improvement by Intermittent Fasting in People with Elevated Baseline Red Cell Distribution Width: A Secondary Analysis of the WONDERFUL Randomized Controlled Trial"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2656-0263","authenticated-orcid":false,"given":"Benjamin D.","family":"Horne","sequence":"first","affiliation":[{"name":"Intermountain Medical Center Heart Institute, Salt Lake City, UT 84107, USA"},{"name":"Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph B.","family":"Muhlestein","sequence":"additional","affiliation":[{"name":"Intermountain Medical Center Heart Institute, Salt Lake City, UT 84107, USA"},{"name":"Cardiology Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi T.","family":"May","sequence":"additional","affiliation":[{"name":"Intermountain Medical Center Heart Institute, Salt Lake City, UT 84107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6659-5332","authenticated-orcid":false,"given":"Viet T.","family":"Le","sequence":"additional","affiliation":[{"name":"Intermountain Medical Center Heart Institute, Salt Lake City, UT 84107, USA"},{"name":"Department of Physician Assistant Studies, College of Medical and Health Professional Science, Rocky Mountain University of Health Professions, Provo, UT 84606, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tami L.","family":"Bair","sequence":"additional","affiliation":[{"name":"Intermountain Medical Center Heart Institute, Salt Lake City, UT 84107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sterling T.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Intermountain Central Laboratory, Intermountain Medical Center, Salt Lake City, UT 84107, USA"},{"name":"Department of Pathology, University of Utah, Salt Lake City, UT 84132, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirk U.","family":"Knowlton","sequence":"additional","affiliation":[{"name":"Intermountain Medical Center Heart Institute, Salt Lake City, UT 84107, USA"},{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey L.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Intermountain Medical Center Heart Institute, Salt Lake City, UT 84107, USA"},{"name":"Cardiology Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1001\/jamainternmed.2017.0936","article-title":"Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults: A randomized clinical trial","volume":"177","author":"Trepanowski","year":"2017","journal-title":"JAMA Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1093\/ajcn\/nqy196","article-title":"Effects of intermittent and continuous calorie restriction on body weight and metabolism over 50 wk: A randomized controlled trial","volume":"108","author":"Sookthai","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e180756","DOI":"10.1001\/jamanetworkopen.2018.0756","article-title":"Effect of intermittent compared with continuous energy restricted diet on glycemic control in patients with type 2 diabetes. A randomized noninferiority trial","volume":"1","author":"Carter","year":"2018","journal-title":"JAMA Netw. Open"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1093\/ajcn\/nqab058","article-title":"The effect of intermittent energy restriction on weight loss and diabetes risk markers in women with a history of gestational diabetes: A 12-month randomized control trial","volume":"114","author":"Gray","year":"2021","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1016\/j.cmet.2018.04.010","article-title":"Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes","volume":"27","author":"Sutton","year":"2018","journal-title":"Cell Metab."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Jamshed, H., Beyl, R.A., Della Manna, D.L., Yang, E.S., Ravussin, E., and Peterson, C.M. (2019). Early time-restricted feeding improves 24-h glucose levels and affects markers of the circadian clock, aging, and autophagy in humans. Nutrients, 11.","DOI":"10.3390\/nu11061234"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1002\/oby.22449","article-title":"Time-restricted feeding improves glucose tolerance in men at risk for type 2 diabetes: A randomized crossover trial","volume":"27","author":"Hutchison","year":"2019","journal-title":"Obesity"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cai, H., Qin, Y.L., Shi, Z.Y., Chen, J.H., Zeng, M.J., Zhou, W., Chen, R.Q., and Chen, Z.Y. (2019). Effects of alternate-day fasting on body weight and dyslipidaemia in patients with non-alcoholic fatty liver disease: A randomised controlled trial. BMC Gastroenterol., 19.","DOI":"10.1186\/s12876-019-1132-8"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"oeab026","DOI":"10.1093\/ehjopen\/oeab026","article-title":"Randomized controlled trial of once-per-week intermittent fasting for health improvement: The WONDERFUL Trial","volume":"1","author":"Bartholomew","year":"2021","journal-title":"Eur. Heart J. Open"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/j.amjcard.2012.01.379","article-title":"Relation of routine, periodic fasting to risk of diabetes mellitus and coronary artery disease in patients undergoing coronary angiography","volume":"109","author":"Horne","year":"2012","journal-title":"Am. J. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bartholomew, C.L., Muhlestein, J.B., Anderson, J.L., May, H.T., Knowlton, K.U., Bair, T.L., Le, V.T., Bailey, B.W., and Horne, B.D. (2021). Association of periodic fasting lifestyles with survival and incident major adverse cardiovascular events in patients undergoing cardiac catheterization. Eur. J. Prev. Cardiol., zwaa050.","DOI":"10.1093\/eurjpc\/zwaa050"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1001\/jama.2020.3908","article-title":"Limited evidence for the health effects and safety of intermittent fasting among patients with type 2 diabetes mellitus","volume":"324","author":"Horne","year":"2020","journal-title":"JAMA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.amjcard.2006.08.015","article-title":"Usefulness of a complete blood count-derived risk score to predict incident mortality in patients with suspected cardiovascular disease","volume":"99","author":"Anderson","year":"2007","journal-title":"Am. J. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1097\/TA.0b013e3182826f02","article-title":"Red cell distribution width is predictive of mortality in trauma patients","volume":"74","author":"Majercik","year":"2013","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"416","DOI":"10.3109\/15412555.2012.758697","article-title":"Red blood cell distribution and survival in patients with chronic obstructive pulmonary disease","volume":"10","author":"Seyhan","year":"2013","journal-title":"COPD"},{"key":"ref_16","first-page":"E402","article-title":"Red blood cell distribution width and cardiovascular diseases","volume":"7","author":"Danese","year":"2015","journal-title":"J. Thorac. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e120183","DOI":"10.1172\/jci.insight.120183","article-title":"Extreme erythrocyte macrocytic and microcytic percentages are highly predictive of morbidity and mortality","volume":"3","author":"Horne","year":"2018","journal-title":"JCI Insight"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1001\/archinternmed.2009.11","article-title":"Red blood cell distribution width and the risk of death in middle-aged and older adults","volume":"169","author":"Patel","year":"2009","journal-title":"Arch. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e2022058","DOI":"10.1001\/jamanetworkopen.2020.22058","article-title":"Association of red blood cell distribution width with mortality risk in hospitalized adults with SARS-CoV-2 infection","volume":"3","author":"Foy","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1001\/archinternmed.2009.55","article-title":"Red blood cell distribution width and mortality risk in a community-based prospective cohort","volume":"169","author":"Perlstein","year":"2009","journal-title":"Arch. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.numecd.2012.09.007","article-title":"Randomized cross-over trial of short-term water-only fasting: Metabolic and cardiovascular consequences","volume":"23","author":"Horne","year":"2013","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.cca.2015.05.021","article-title":"Persistent increase in red cell size distribution width after acute diseases: A biomarker of hypoxemia?","volume":"448","author":"Horrow","year":"2015","journal-title":"Clin. Chim. Acta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/ajh.23982","article-title":"Modulation of red blood cell population dynamics is a fundamental homeostatic response to disease","volume":"90","author":"Patel","year":"2015","journal-title":"Am. J. Hematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"ref_25","unstructured":"Hanson, R.W., and Mehlman, M.A. (1976). Gluconeogenesis and its disorders in man. Gluconeogenesis: Its Regulation in Mammalian Species, Wiley."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Walton, C.M., Jacobsen, S.M., Dallon, B.W., Saito, E.R., Bennett, S.L.H., Davidson, L.E., Thomson, D.M., Hyldahl, R.D., and Bikman, B.T. (2020). Ketones elicit distinct alterations in adipose mitochondrial bioenergetics. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176255"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/12\/4407\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:44:03Z","timestamp":1760168643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/12\/4407"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,9]]},"references-count":26,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["nu13124407"],"URL":"https:\/\/doi.org\/10.3390\/nu13124407","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2021,12,9]]}}}