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In the present study, we subjected 11\u00a0healthy men (aged 18\u201340\u00a0years) to two 2\u00a0week cycles of oral clenbuterol (80\u00a0\u00b5g\u00a0day<jats:sup>\u22121<\/jats:sup>) or placebo, separated by a 3\u00a0week washout. During each cycle, we assessed body composition, cardiorespiratory fitness, sprint power output, cardiac left ventricular mass and intravascular blood volume. We obtained vastus lateralis muscle biopsies and analysed them for protein content, 3\u2010hydroxyacyl CoA dehydrogenase (HAD) activity, oxidative phosphorylation complex (OXPHOS) abundance, platelet endothelial cell adhesion molecule (PECAM\u20101) abundance and \u03b2<jats:sub>2<\/jats:sub>\u2010adrenergic signalling. Compared to placebo, clenbuterol induced a 0.91\u00a0kg lean mass gain (95% confidence interval\u00a0=\u00a00.02\u20131.81, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) but had no effect on fat mass. Clenbuterol reduced maximal oxygen uptake by 7% (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and exercise capacity by 4% (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) but had no effects on sprint power output, left ventricular mass, intravascular blood volume or haemoglobin mass. Clenbuterol increased muscle protein content (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and PECAM\u20101 abundance (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) but repressed HAD activity (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and OXPHOS complex V abundance (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Clenbuterol markedly activated muscle protein kinase A (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and phosphorylated ribosomal protein S6 (Ser235\/236) but this effect declined during the 2\u00a0week cycle. Although a 2\u00a0week clenbuterol cycle effectively induces lean mass gain and muscle protein accretion, it negatively affects cardiorespiratory fitness, represses muscle oxidative capacity, and induces tolerance in \u03b2<jats:sub>2<\/jats:sub>\u2010adrenergic signalling and ribosomal protein S6 phosphorylation. The adverse effects of clenbuterol along with its muscle anabolic actions justify its prohibition in elite sports.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70108-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Clenbuterol, a potent \u03b2<jats:sub>2<\/jats:sub>\u2010adrenergic agonist, has purported fat\u2010burning and muscle accretion properties. However, its purported effects, along with its potential adverse effects on cardiorespiratory fitness, remain unexplored in humans.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A short 2\u00a0week clenbuterol cycle induces lean mass gain and muscle protein accretion in healthy young men.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Clenbuterol induces \u03b2<jats:sub>2<\/jats:sub>\u2010adrenergic signalling and phosphorylates RpS6<jats:sup>Ser235\/236<\/jats:sup> in skeletal muscle, but this signalling response is attenuated with repeated exposure.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Clenbuterol negatively affects cardiorespiratory fitness and represses muscle oxidative capacity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Clenbuterol does not affect left ventricular mass, intravascular blood volume or haemoglobin mass.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp289023","type":"journal-article","created":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T18:04:53Z","timestamp":1757873093000},"page":"5529-5545","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Clenbuterol induces lean mass and muscle protein accretion, but attenuates cardiorespiratory fitness and desensitizes muscle \u03b2<sub>2<\/sub>\u2010adrenergic signalling"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6201-2483","authenticated-orcid":false,"given":"Morten","family":"Hostrup","sequence":"first","affiliation":[{"name":"The August Krogh Section for Human and Molecular Physiology, Department of Nutrition, Exercise and Sports University of Copenhagen  Copenhagen 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