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

Abstract

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; p < 0.00001), appendicular LM (SMD = 0.35; p < 0.00001), leg strength (SMD = 0.65; p < 0.00001), and walking capability (SMD = 0.33; p = 0.0006). Meta-regression analyses showed that changes in appendicular LM were significantly associated with the effect sizes of leg strength (β = 0.08; p = 0.003) and walking capability (β = 0.17; p = 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.

Keywords: exercise training; lean body mass; physical function; protein supplement; sarcopenia.

Figure 1

Flow chart of enrolled studies.

Figure 2

Forest plot summarizing effects of protein supplement (PS) plus muscle strengthening exercise (MSE) on changes of muscle mass, body composition, and physical function at each follow up duration. Each point estimate at each follow up duration (square) and during an overall duration (diamond) presents the combined effect (standard mean difference) of the outcome measure where indicated, with 95% CI (horizontal line). Results plotted on the right-hand side indicate effects in favor of PS plus Ex. The combined effects analyzed by a fixed- or random-effect model are denoted by green and blue colors, respectively; and a black colored square denotes that the combined effect is derived from a single study. 95% CI = 95% confidence interval; Std = standard; IV = inverse variance; SPPB = short physical performance battery.

Figure 3

Multivariate meta-regression between percentage change in lean body mass and effects of PS plus MSE on leg strength. Each circle represents an independent comparison. The size of each circle is proportional to that study’s weight (inverse variance weighted). The regression prediction is represented by the solid line for effect size (SMD) of leg strength. Dotted lines represent the 95% CI. The metaregression model was adjusted for age, methodological quality, and follow-up time of each comparison. PS, protein supplementation; MSE, muscle strengthening exercise; SMD, standard mean difference.

Figure 4

Multivariate meta-regression between percentage change in appendicular lean mass and effects of PS plus MSE on leg strength. Each circle represents an independent comparison. The size of each circle is proportional to that study’s weight (inverse variance weighted). The regression prediction is represented by the solid line for effect size (SMD) of leg strength. Dotted lines represent the 95% CI. The metaregression model was adjusted for age, methodological quality, and follow-up time of each comparison. PS, protein supplementation; MSE, muscle strengthening exercise; SMD, standard mean difference.

Figure 5

Multivariate meta-regression between percentage change in appendicular lean mass and effects of PS plus MSE on walk capability. Each circle represents an independent comparison. The size of each circle is proportional to that study’s weight (inverse variance weighted). The regression prediction is represented by the solid line for effect size (SMD) of walk capability. Dotted lines represent the 95% CI. The metaregression model was adjusted for age, methodological quality, and follow-up time of each comparison. PS, protein supplementation; MSE, muscle strengthening exercise; SMD, standard mean difference.

Figure 6

Funnel plots of the intervention effects for (A) lean body mass, (B) leg strength, and (C) walk capability. Each circle represents an independent comparison, with the x-axis representing standard mean difference (SMD) the over control comparisons and the y-axis showing the standard error (SE) of SMD. The vertical dotted line indicates the mean value of the SMDs.