{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:06:46Z","timestamp":1789510006124,"version":"build-2803163510"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"InsideTracker"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Exercise is effective toward delaying or preventing chronic disease, with a large body of evidence supporting its effectiveness. However, less is known about the specific healthspan-promoting effects of exercise on blood biomarkers in the disease-free population. In this work, we examine 23,237 generally healthy individuals who self-report varying weekly running volumes and compare them to 4,428 generally healthy sedentary individuals, as well as 82 professional endurance runners. We estimate the significance of differences among blood biomarkers for groups of increasing running levels using analysis of variance (ANOVA), adjusting for age, gender, and BMI. We attempt and add insight to our observational dataset analysis via two-sample Mendelian randomization (2S-MR) using large independent datasets. We find that self-reported running volume associates with biomarker signatures of improved wellness, with some serum markers apparently being principally modified by BMI, whereas others show a dose-effect with respect to running volume. We further detect hints of sexually dimorphic serum responses in oxygen transport and hormonal traits, and we also observe a tendency toward pronounced modifications in magnesium status in professional endurance athletes. Thus, our results further characterize blood biomarkers of exercise and metabolic health, particularly regarding dose-effect relationships, and better inform personalized advice for training and performance.<\/jats:p>","DOI":"10.1371\/journal.pone.0293631","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T18:21:49Z","timestamp":1700072509000},"page":"e0293631","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dose response of running on blood biomarkers of wellness in generally healthy individuals"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8977-7470","authenticated-orcid":true,"given":"Bartek","family":"Nogal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Vinogradova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Jorge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Torkamani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Fabian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil","family":"Blander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"issue":"5","key":"pone.0293631.ref001","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1161\/CIRCRESAHA.118.312669","article-title":"Sedentary Behavior, Exercise, and Cardiovascular Health","volume":"124","author":"CJ Lavie","year":"2019","journal-title":"Circ Res"},{"key":"pone.0293631.ref002","doi-asserted-by":"crossref","first-page":"E38","DOI":"10.5888\/pcd18.170354","article-title":"Percentage of Deaths Associated With Inadequate Physical Activity in the United States","volume":"15","author":"SA Carlson","year":"2018","journal-title":"Prev Chronic Dis"},{"issue":"5","key":"pone.0293631.ref003","doi-asserted-by":"crossref","first-page":"860","DOI":"10.18632\/aging.100901","article-title":"Exercise: a \"new drug\" for elderly patients with chronic heart failure","volume":"8","author":"R Antonicelli","year":"2016","journal-title":"Aging (Albany NY)"},{"key":"pone.0293631.ref004","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.coph.2021.05.006","article-title":"Exercise as a drug for glucose management and prevention in type 2 diabetes mellitus","volume":"59","author":"P Sgro","year":"2021","journal-title":"Curr Opin Pharmacol"},{"issue":"1","key":"pone.0293631.ref005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1476-5381.2012.01970.x","article-title":"Exercise acts as a drug; the pharmacological benefits of exercise","volume":"167","author":"J Vina","year":"2012","journal-title":"Br J Pharmacol"},{"issue":"10","key":"pone.0293631.ref006","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1519\/JSC.0000000000002122","article-title":"Biomarkers in Sports and Exercise: Tracking Health, Performance, and Recovery in Athletes","volume":"31","author":"EC Lee","year":"2017","journal-title":"J Strength Cond Res"},{"issue":"7","key":"pone.0293631.ref007","article-title":"Effects of Exercise Training on Cardiorespiratory Fitness and Biomarkers of Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"4","author":"X Lin","year":"2015","journal-title":"J Am Heart Assoc"},{"key":"pone.0293631.ref008","doi-asserted-by":"crossref","first-page":"103318","DOI":"10.1016\/j.ebiom.2021.103318","article-title":"Clinical biomarkers and associations with healthspan and lifespan: Evidence from observational and genetic data","volume":"66","author":"X Li","year":"2021","journal-title":"EBioMedicine"},{"key":"pone.0293631.ref009","doi-asserted-by":"crossref","first-page":"111014","DOI":"10.1016\/j.exger.2020.111014","article-title":"Circulating biomarkers characterizing physical frailty: CRP, hemoglobin, albumin, 25OHD and free testosterone as best biomarkers. 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