The Role of Muscle Mass Gain Following Protein Supplementation Plus Exercise Therapy in Older Adults with Sarcopenia and Frailty Risks: A Systematic Review and Meta-Regression Analysis of Randomized Trials

Aging and frailty are associated with a high risk of lean mass (LM) loss, which leads to physical disability and can be effectively alleviated by protein supplementation (PS) and muscle strengthening exercise (MSE). In this study, the associations between LM gain and PS + MSE efficacy (measured using physical outcomes) in elderly patients with a high risk of sarcopenia or frailty were identified. A comprehensive search of online databases was performed to identify randomized controlled trials (RCTs) reporting the efficacy of PS + MSE in elderly patients with sarcopenia or frailty. The included RCTs were analyzed using meta-analysis and risk of bias assessment. We finally included 19 RCTs in this meta-analysis with a median (range/total) Physiotherapy Evidence Database score of 7/10 (5-9/10). The PS + MSE group exhibited significant improvements in the whole-body LM (standard mean difference (SMD) = 0.66; <i>p</i> < 0.00001), appendicular LM (SMD = 0.35; <i>p</i> < 0.00001), leg strength (SMD = 0.65; <i>p</i> < 0.00001), and walking capability (SMD = 0.33; <i>p</i> = 0.0006). Meta-regression analyses showed that changes in appendicular LM were significantly associated with the effect sizes of leg strength (β = 0.08; <i>p</i> = 0.003) and walking capability (β = 0.17; <i>p</i> = 0.04), respectively. Our findings suggest that LM gain after PS + MSE significantly contributes to the efficacy of the intervention in terms of muscle strength and physical mobility in elderly patients with a high risk of sarcopenia or frailty.