Creatine supplementation for optimisation of physical function in the patient at risk of functional disability: A systematic review and meta-analysis

Background The efficacy of creatine replacement through supplementation for the optimisation of physical function in the population at risk of functional disability is unclear. Methods We conducted a systematic literature search of MEDLINE, EMBASE, Cochrane Library and CINAHL until November 2022. Studies included were randomised controlled trials comparing the use of creatine supplementation with placebo in older adults and adults with chronic disease. The primary outcome was physical function measured by the sit-to-stand test after pooling data using random effects modelling. We also performed a Bayesian meta-analysis to describe the treatment effect in probability terms. Secondary outcomes included other measures of physical function, muscle function and body composition. The risk of bias was assessed using the Cochrane risk-of-bias tool. Results We identified 33 RCTs, comprising 1076 participants. From 6 trials reporting the primary outcome, the pooled standardised mean difference was 0.51 (95% CI 0.01 to 1.00; I =62%; p=0.04); using weakly informative priors, the posterior probability that creatine supplementation improves physical function was 66.7%. Upper body muscle strength (SMD 0.25, 95% CI 0.06 to 0.44; I =0%; p=0.01), handgrip strength (SMD 0.23, 95% CI 0.01 to 0.45; I =0%; p=0.04) and lean tissue mass (MD 1.08kg; 95% CI 0.77 to 1.38; I =26%; p<0.01) improved with creatine supplementation. The quality of evidence for all outcomes was low or very low due to a high risk of bias. Conclusion Creatine supplementation improves sit-to-stand performance, muscle function and lean tissue mass. It is crucial to conduct high-quality prospective RCTs to confirm these hypotheses (Prospero number, CRD42023354929). ### Competing Interest Statement Conflict of interest statement: ZP has received honoraria for consultancy from Nestle, Nutriticia, Faraday Pharmaceuticals and Fresenius-Kabi, and speaker fees from Baxter, Fresenius-Kabi, Nutriticia and Nestle. RP has received research grants and/or honoraria from Edwards Lifesciences and Intersurgical UK. ### Clinical Protocols ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript