Influence of age, sex, and type of exercise on the efficacy of creatine supplementation on lean body mass: A systematic review and meta-analysis of randomized clinical trials

Creatine supplementation has been shown to increase measures of lean body mass (LBM); however, there often is high heterogeneity across individual studies. Therefore, the aim of this study was to systematically review and meta-analyze randomized controlled trials (RCTs) investigating creatine supplementation on LBM. Subanalyses were performed based on age, sex, and type of exercise. Based on PRISMA guidelines, we searched the following databases: Pubmed, SPORTDiscus, Web of Science, and Scopus (PROSPERO register: CRD42020207122) until May 2022. RCTs for investigation of creatine supplementation on LBM were included. Animal studies and studies on individuals with specific diseases were excluded. Thirty-five studies were included, with 1192 participants. Overall (i.e., inclusion of all studies with and without exercise training interventions) revealed that creatine increased LBM by 0.68 kg (95% confidence interval [CI], 0.26-1.11). Subanalyses revealed greater gains in LBM when creatine was combined with resistance training (mean difference [MD], 1.10 kg; 95% CI, 0.56-1.65), regardless of age. There was no statistically significant effect of creatine on LBM when combined with mixed exercise (MD, 0.74 kg; 95% CI, -3.89 to 5.36) or without exercise (MD, 0.03 kg; 95% CI, -0.65 to 0.70). Further subanalyses found that males on creatine increased LBM by 1.46 kg (95% CI, 0.47-2.46), compared with a non-significant increase of 0.29 kg (95% CI, -0.43 to 1.01) for females. In conclusion, the addition of creatine supplementation to a resistance training program increases LBM. During a resistance training program, males on creatine respond more favorably than females.