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This study assessed whether a comprehensive lifestyle intervention, including high volumes of supervised exercise, could improve health outcomes. Eight volunteers with lifestyle\u2010related diseases received a 6\u2010month lifestyle intervention consisting of 8000\u201310\u2009000 steps\/day, 6 moderate\u2010intensity endurance and 3 resistance training sessions per week, a 5\u2010week long hike, and dietary advice. This was followed by 7\u2009months of limited remote supervision, ending 13\u2009months from baseline. The participants (3 females, 5 males; mean age 42.9\u2009years) had conditions including type 2 diabetes (T2D), depression\/stress, and metabolic syndrome (MS). After 6\u2009months, body weight decreased significantly by 23\u2009kg (95% CI; \u221233.7 to \u221212.2), with a minor non\u2010significant decrease in lean body mass of 1.96\u2009kg (95% CI; \u22124.34 to 0.27). Maximal oxygen consumption (VO<jats:sub>2<\/jats:sub>max) increased by 18.5\u2009mL\/O<jats:sub>2<\/jats:sub>\/kg\/min. (95% CI; 13.8\u201323.1) and systolic and diastolic blood pressures decreased by 33 (95% CI; \u221239 to \u221226) and 18\u2009mmHg (95% CI; \u221223 to \u221214), respectively. Three of the 4 participants with T2D had normalized glycated hemoglobin (HbA1c) levels, and all showed improved 2\u2010h oral glucose tolerance (OGTT) without pharmacological treatment. Participants with T2D continued to lower HbA1c during the 7\u2010month follow\u2010up period. This 6\u2010month lifestyle intervention restored metabolic health and improved cardiovascular health in 8 participants with lifestyle\u2010related diseases while reducing the need for pharmacological treatments. These findings suggest that comprehensive lifestyle changes can reverse several medical conditions caused by evolutionary mismatch.<\/jats:p>","DOI":"10.1111\/sms.14770","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T23:38:43Z","timestamp":1734565123000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evolutionary Mismatch and Lifestyle\u2010Related Diseases: A Study of a 6\u2010Month Intensive Lifestyle Intervention"],"prefix":"10.1111","volume":"34","author":[{"given":"Christopher Scott","family":"MacDonald","sequence":"first","affiliation":[{"name":"Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet University of Copenhagen  Copenhagen Denmark"},{"name":"Section for Biostatistics and Evidence\u2010Based Research, The Parker Institute Bispebjerg and Frederiksberg Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia Aagaard","family":"Bennekou","sequence":"additional","affiliation":[{"name":"Grace Health and Performance Enhancement  H\u00f8rsholm Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina Mai","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Section for Biostatistics and Evidence\u2010Based Research, The Parker Institute Bispebjerg and Frederiksberg Hospital  Copenhagen Denmark"},{"name":"Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders Ellek\u00e6r","family":"Junker","sequence":"additional","affiliation":[{"name":"Gastro Unit University Hospital Hvidovre  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tor","family":"Biering\u2010S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Cardiovascular Non\u2010Invasive Imaging Research Laboratory, Department of Cardiology Copenhagen University Hospital\u2013Herlev and Gentofte  Copenhagen Denmark"},{"name":"Steno Diabetes Center Copenhagen  Copenhagen Denmark"},{"name":"Department of Cardiology Copenhagen University Hospital\u2e3aRigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Langberg","sequence":"additional","affiliation":[{"name":"Department of Public Health University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Christensen","sequence":"additional","affiliation":[{"name":"Section for Biostatistics and Evidence\u2010Based Research, The Parker Institute Bispebjerg and Frederiksberg Hospital  Copenhagen Denmark"},{"name":"Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Department of Human Evolutionary Biology Harvard University  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Zachariae","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy Herlev and Gentofte Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8072-3318","authenticated-orcid":false,"given":"Jannik Langtved","family":"Pallisgaard","sequence":"additional","affiliation":[{"name":"JP Cardiology Kongens Lyngby  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"WHO Non Communicable Diseases(2023) https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/noncommunicable\u2010diseases."},{"key":"e_1_2_11_3_1","unstructured":"WHO Noncommunicable Diseases: Risk Factors https:\/\/www.who.int\/data\/gho\/data\/themes\/topics\/topic\u2010details\/GHO\/ncd\u2010risk\u2010factors."},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.evolhumbehav.2020.04.001"},{"key":"e_1_2_11_5_1","volume-title":"The Story of the Human Body. 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