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Evidence of effectiveness of creatine supplementation in improving several clinical conditions is now substantial, and we review it in this paper. In hereditary diseases where its synthesis is impaired, creatine has a disease\u2010modifying capacity, especially when started soon after birth. Strong evidence, including a Cochrane meta\u2010analysis, shows that it improves muscular strength and general well\u2010being in muscular dystrophies. Significant evidence exists also of its effectiveness in secondary prevention of statin myopathy and of treatment\u2010resistant depression in women. Vegetarians and vegans do not consume any dietary creatine and must synthesize all they need, spending most of their methylation capacity. Nevertheless, they have a lower muscular concentration of creatine. Creatine supplementation has proved effective in increasing muscular and neuropsychological performance in vegetarians or vegans and should, therefore, be recommended especially in those of them who are athletes, heavy\u2010duty laborers or who undergo intense mental effort. Convincing evidence also exists of creatine effectiveness in muscular atrophy and sarcopenia in the elderly, and in brain energy shortage (mental fatigue, sleep deprivation, environmental hypoxia as in mountain climbing, and advanced age). Furthermore, we review more randomized, placebo\u2010controlled trials showing that creatine supplementation is safe up to 20\u2009g\/d, with a possible caveat only in people with kidney disease. We trust that the evidence we review will be translated into clinical practice and will spur more research on these subjects.<\/jats:p>","DOI":"10.1002\/med.21590","type":"journal-article","created":{"date-parts":[[2019,4,23]],"date-time":"2019-04-23T04:26:54Z","timestamp":1555993614000},"page":"2427-2459","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Beyond sports: Efficacy and safety of creatine supplementation in pathological or paraphysiological conditions of brain and muscle"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5971-2200","authenticated-orcid":false,"given":"Maurizio","family":"Balestrino","sequence":"first","affiliation":[{"name":"Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno\u2010Infantili (DINOGMI) University of Genova  Genova Italy"},{"name":"Clinica Neurologica IRCCS Ospedale\u00a0Policlinico San Martino  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Adriano","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno\u2010Infantili (DINOGMI) University of Genova  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,23]]},"reference":[{"key":"e_1_2_10_1_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-011-0877-3"},{"key":"e_1_2_10_1_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-011-0856-8"},{"key":"e_1_2_10_1_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.3.1107"},{"key":"e_1_2_10_1_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20280"},{"key":"e_1_2_10_1_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/72.2.607S"},{"key":"e_1_2_10_1_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-016-2188-1"},{"key":"e_1_2_10_1_8_1","first-page":"pp. 265","volume-title":"L'alimentazione per l'esercizio fisico e lo sport","author":"Giampietro M","year":"2009"},{"key":"e_1_2_10_1_9_1","doi-asserted-by":"publisher","DOI":"10.3382\/ps.2013-03441"},{"key":"e_1_2_10_1_10_1","unstructured":"Organisation for Economic Co\u2010operation and Development.World meat projections.https:\/\/www.oecd\u2010ilibrary.org\/agriculture\u2010and\u2010food\/oecd\u2010fao\u2010agricultural\u2010outlook\u20102017\u20102026\/world\u2010meat\u2010projections_agr_outlook\u20102017\u2010table70\u2010en. 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