Beyond sports: Efficacy and safety of creatine supplementation in pathological or paraphysiological conditions of brain and muscle

Med Res Rev. 2019 Nov;39(6):2427-2459. doi: 10.1002/med.21590. Epub 2019 Apr 23.


Creatine is pivotal in energy metabolism of muscle and brain cells, both in physiological and in pathological conditions. Additionally, creatine facilitates the differentiation of muscle and neuronal cells. 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-modifying capacity, especially when started soon after birth. Strong evidence, including a Cochrane meta-analysis, shows that it improves muscular strength and general well-being in muscular dystrophies. Significant evidence exists also of its effectiveness in secondary prevention of statin myopathy and of treatment-resistant 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-duty 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-controlled trials showing that creatine supplementation is safe up to 20 g/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.

Keywords: brain; creatine; muscle; phosphocreatine; therapy.

Publication types

  • Review

MeSH terms

  • Brain / drug effects
  • Brain / pathology*
  • Creatine / administration & dosage
  • Creatine / pharmacology*
  • Dietary Supplements*
  • Humans
  • Muscles / drug effects
  • Muscles / pathology*
  • Sports*
  • Treatment Outcome


  • Creatine