{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:04:37Z","timestamp":1790658277711,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Muscle disuse leads to muscle atrophy and a decrease in muscle function that is primarily driven by reduced muscle protein synthesis (MPS). The aim of this systematic review and meta\u2010analysis was to examine the effect of different models of muscle disuse on rates of MPS. A literature search was conducted in PubMed, Web of Science, Scopus and Cochrane Library. Eligible randomized and non\u2010randomized controlled trials compared the effect of bed rest (BR), unilateral lower limb immobilization (ULLI), and 6\u00b0 head\u2010down tilt (HDT) on pre\u2013post muscle disuse changes in MPS in adults. Using the random and fixed effects inverse\u2010variance model, we calculated the mean difference (MD) in the effect of BR on mixed MPS and ULLI on myofibrillar MPS (MyoPS) (both expressed as fractional synthetic rate,%\/h). The effect of HDT on MPS was examined through a narrative synthesis of data. A total of 16 studies were included in the systematic review and 13 in the meta\u2010analysis. A significant reduction in mixed MPS was observed after BR (\n                    <jats:italic>k<\/jats:italic>\n                    \u00a0=\u00a04; MD: \u22120.017%\/h, 95% CI: \u22120.023 to \u22120.011,\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u00a0=\u00a024%,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00.01) and a significant reduction in MyoPS was observed after ULLI (\n                    <jats:italic>k<\/jats:italic>\n                    \u00a0=\u00a09; MD: \u22120.015%\/h, 95% CI: \u22120.021 to \u22120.008,\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u00a0=\u00a094%,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00.01). HDT led to reductions in both mixed MPS and MyoPS. A comparable reduction in mixed MPS and MyoPS was observed between different models of muscle disuse.\n                  <\/jats:p>","DOI":"10.1113\/ep092474","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T16:11:18Z","timestamp":1761840678000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The effect of bed rest, unilateral limb immobilization and head\u2010down tilt on muscle protein synthesis: A systematic review and meta\u2010analysis"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6264-9388","authenticated-orcid":false,"given":"Konstantinos","family":"Prokopidis","sequence":"first","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul T.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Sport and Exercise Sciences, Institute of Sport Manchester Metropolitan University  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2281-6479","authenticated-orcid":false,"given":"Colleen S.","family":"Deane","sequence":"additional","affiliation":[{"name":"Human Development &amp; Health, Faculty of Medicine University of Southampton, Southampton General Hospital  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5875-8397","authenticated-orcid":false,"given":"Oliver C.","family":"Witard","sequence":"additional","affiliation":[{"name":"Centre for Human &amp; Applied Physiological Sciences, Faculty of Life Sciences and Medicine King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"Church","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Donald W. Reynolds Institute on Aging, Center for Translational Research in Aging and Longevity University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"issue":"8","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1152\/japplphysiol.00799.2015","article-title":"Fourteen days of bed rest induces a decline in satellite cell content and robust atrophy of skeletal muscle fibers in middle\u2010aged adults","volume":"120","author":"Arentson\u2010Lantz E. 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S.","year":"2022","journal-title":"Journal of Cachexia, Sarcopenia and Muscle"},{"issue":"3","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1096\/fj.04-2640fje","article-title":"Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle","volume":"19","author":"Cuthbertson D.","year":"2005","journal-title":"The Federation of American Societies for Experimental Biology Journal"},{"issue":"12","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1042\/CS20231198","article-title":"Skeletal muscle immobilisation\u2010induced atrophy: Mechanistic insights from human studies","volume":"138","author":"Deane C. 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J.","year":"2019","journal-title":"Cochrane Handbook for Systematic Reviews of Interventions"},{"issue":"4","key":"e_1_2_10_10_1","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.15958","article-title":"Lower basal and postprandial muscle protein synthesis after 2 weeks single\u2010leg immobilization in older men: No protective effect of anti\u2010inflammatory medication","volume":"12","author":"Dideriksen K.","year":"2024","journal-title":"Physiological Reports"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2021.633987","article-title":"The aging muscle in experimental bed rest: A systematic review and meta\u2010analysis","volume":"8","author":"Di Girolamo F. G.","year":"2021","journal-title":"Frontiers in Nutrition"},{"issue":"1","key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/apha.12699","article-title":"May bed rest cause greater muscle loss than limb immobilization?","volume":"218","author":"Dirks M. 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J.","year":"2012","journal-title":"American Journal of Physiology\u2010Endocrinology and Metabolism"},{"key":"e_1_2_10_15_1","first-page":"89","article-title":"A nonparametric \u201ctrim and fill\u201d method of accounting for publication bias in meta\u2010analysis","volume":"95","author":"Duval S.","year":"2000","journal-title":"Journal of the American Statistical Association"},{"issue":"5","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1093\/ajcn\/nqaa229","article-title":"High\u2010dose leucine supplementation does not prevent muscle atrophy or strength loss over 7 days of immobilization in healthy young males","volume":"112","author":"Edwards S. 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J.","year":"2018","journal-title":"Journal of Applied Physiology"},{"key":"e_1_2_10_30_1","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page M. J.","year":"2021","journal-title":"British Medical Journal"},{"issue":"5","key":"e_1_2_10_31_1","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1002\/jcsm.13284","article-title":"Short\u2010term disuse does not affect postabsorptive or postprandial muscle protein fractional breakdown rates","volume":"14","author":"Pavis G. F.","year":"2023","journal-title":"Journal of Cachexia, Sarcopenia and Muscle"},{"issue":"24","key":"e_1_2_10_32_1","doi-asserted-by":"crossref","first-page":"5341","DOI":"10.1113\/jphysiol.2014.273615","article-title":"CrossTalk proposal: The dominant mechanism causing disuse muscle atrophy is decreased protein synthesis","volume":"592","author":"Phillips S. M.","year":"2014","journal-title":"The Journal of Physiology"},{"issue":"6","key":"e_1_2_10_33_1","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1152\/japplphysiol.00147.2023","article-title":"The effects of single\u2010leg disuse on skeletal muscle strength and size in the nonimmobilized leg of uninjured adults: A meta\u2010analysis","volume":"134","author":"Preobrazenski N.","year":"2023","journal-title":"Journal of Applied Physiology"},{"issue":"2","key":"e_1_2_10_34_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/jcsm.13431","article-title":"Bed\u2010rest and exercise remobilization: Concurrent adaptations in muscle glucose and protein metabolism","volume":"15","author":"Shur N. F.","year":"2024","journal-title":"Journal of Cachexia, Sarcopenia and Muscle"},{"key":"e_1_2_10_35_1","first-page":"1744","article-title":"Skeletal muscle energetics and mitochondrial function are impaired following 10 days of bed rest in older adults","volume":"75","author":"Standley R. A.","year":"2020","journal-title":"The Journals of Gerontology: Series A"},{"key":"e_1_2_10_36_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.i4919","article-title":"The risk of bias in non\u2010randomized studies\u2013of interventions (ROBINS\u2010I) assessment tool","volume":"355","author":"Sterne J.","year":"2016","journal-title":"British Medical Journal"},{"issue":"1","key":"e_1_2_10_37_1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1152\/japplphysiol.91137.2008","article-title":"Artificial gravity maintains skeletal muscle protein synthesis during 21 days of simulated microgravity","volume":"107","author":"Symons T. 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