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To counteract muscle loss, \u03b2\u2010hydroxy \u03b2\u2010methylbutyrate (HMB) supplementation has been proposed as a potential therapy for older adults and various diseases states. This systematic review aimed to investigate the effects and safety of HMB supplementation in relation to muscle mass and function and other clinical outcomes in patients with cancer. A systematic search of MEDLINE, CINAHL, Embase, Cochrane Central Register of Controlled Trials, Scopus, ProQuest, and grey literature for reports published from inception to December 2021 was conducted. Included studies provided supplements containing any dose of HMB to adult patients with active cancer. A synthesis without meta\u2010analysis was conducted using a vote\u2010counting approach based solely on the direction of the effect (i.e. regardless of statistical significance). Risk of bias was assessed for each outcome domain, and evidence from higher\u2010quality studies (i.e. those with either low or moderate risk of bias) was examined. Safety was evaluated using both lower\u2010quality and higher\u2010quality studies. Fifteen studies were included, in which six were randomized controlled trials in patients with various cancer types and treatments. Studies prescribed HMB combined with amino acids (73.3%), HMB in oral nutritional supplements (20.0%), or both supplement types (6.7%); Ca\u2010HMB doses of 3.0\u00a0g\/day were provided in 80.0% of the studies. Four studies had high risk of bias across all outcome domains. Considering the higher\u2010quality studies, evidence of a beneficial effect of HMB supplementation was found in four of four studies for muscle mass, two of two for muscle function, three of three for hospitalization, and five of seven for survival. In contrast, no beneficial effects of HMB on quality of life or body weight was found in two of four and three of five studies, respectively. A limited number of higher\u2010quality studies evaluating the impact of HMB on cancer therapy\u2010related toxicity, inflammation, and tumour response were observed. No serious adverse effects directly related to the nutrition intervention were reported. Although limited, current evidence suggests that HMB supplementation has a beneficial effect on muscle mass and function in patients with cancer. Well\u2010designed trials are needed to further explore the clinical benefit of HMB supplementation in this patient population.<\/jats:p>","DOI":"10.1002\/jcsm.12952","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T23:49:43Z","timestamp":1647560983000},"page":"1623-1641","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Effects of \u03b2\u2010hydroxy \u03b2\u2010methylbutyrate (HMB) supplementation on muscle mass, function, and other outcomes in patients with cancer: a systematic review"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3609-5641","authenticated-orcid":false,"given":"Carla M.","family":"Prado","sequence":"first","affiliation":[{"name":"Human Nutrition Research Unit, Department of Agricultural, Food and Nutritional Science University of Alberta  Edmonton AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5989-0528","authenticated-orcid":false,"given":"Camila E.","family":"Orsso","sequence":"additional","affiliation":[{"name":"Human Nutrition Research Unit, Department of Agricultural, Food and Nutritional Science University of Alberta  Edmonton AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzette L.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Research and Development Abbott Nutrition  Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Atherton","sequence":"additional","affiliation":[{"name":"Centre of Metabolism, Ageing &amp; Physiology (COMAP), Medical Research Council (MRC) Versus Arthritis Centre for Musculoskeletal Ageing Research (CMAR), and National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaas E. 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