Abstract

Creatine Monohydrate (CrM) is a dietary supplement routinely used as an ergogenic aid for sport and training, and as a potential therapeutic aid to augment different disease processes. Despite its increased use in recent years, studies reporting potential adverse outcomes of CrM have been mostly derived from male or mixed sex populations. A systematic search was conducted, which included female participants on CrM, where adverse outcomes were reported, with meta-analysis performed where appropriate. Six hundred and fifty-six studies were identified where creatine supplementation was the primary intervention; fifty-eight were female only studies (9%). Twenty-nine studies monitored for adverse outcomes, with 951 participants. There were no deaths or serious adverse outcomes reported. There were no significant differences in total adverse events, (risk ratio (RR) 1.24 (95% CI 0.51, 2.98)), gastrointestinal events, (RR 1.09 (95% CI 0.53, 2.24)), or weight gain, (mean difference (MD) 1.24 kg pre-intervention, (95% CI −0.34, 2.82)) to 1.37 kg post-intervention (95% CI −0.50, 3.23)), in CrM supplemented females, when stratified by dosing regimen and subject to meta-analysis. No statistically significant difference was reported in measures of renal or hepatic function. In conclusion, mortality and serious adverse events are not associated with CrM supplementation in females. Nor does the use of creatine supplementation increase the risk of total adverse outcomes, weight gain or renal and hepatic complications in females. However, all future studies of creatine supplementation in females should consider surveillance and comprehensive reporting of adverse outcomes to better inform participants and health professionals involved in future trials.

Highlights

  • The creatine kinase circuit is integral to cellular bioenergetics and maintenance of ATP production, especially in skeletal muscle [1,2]

  • We found no mortality or serious adverse events associated with Creatine monohydrate (CrM) supplementation in females, which agrees with previous safety reviews in male or mixed sex populations [22,23,27,86,87,88,89,90,91,92]

  • This review found no evidence that CrM supplementation negatively impacts liver function in females, which corresponds to the findings of other studies and reviews [13,138,145,149,152, 155,156,157]

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Summary

Introduction

The creatine kinase circuit is integral to cellular bioenergetics and maintenance of ATP production, especially in skeletal muscle [1,2]. Creatine monohydrate (CrM) has been used as a dietary supplement to enhance sporting performance, and as a potential therapeutic aid to modify neurodegenerative disease or musculo-skeletal disorders, such as Huntington’s disease [6], amyotrophic lateral sclerosis [7,8], and certain muscular dystrophies [9]. These studies have shown mixed results; from some. After several decades of efficacy studies, in 2017, The International Society of Sports Nutrition (ISSN) concluded that creatine is likely to be more beneficial than harmful to many populations [14]

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