The Effect of Leucine Supplementation on Sarcopenia-Related Measures in Older Adults: A Systematic Review and Meta-Analysis of 17 Randomized Controlled Trials

Abstract

BackgroundThe role of leucine in sarcopenia prevention remains unclear. We aimed to summarize the published data from randomized controlled trials (RCTs) to estimate the effect of leucine supplementation on sarcopenia-related measures in older adults.MethodsA systematic literature search was performed using the electronic databases PubMed, Embase, and Web of Science with restriction to randomized controlled trials design from January 1, 2009 to March 19, 2022. Sarcopenia-related measures included handgrip strength, total lean mass, gait speed, leg press, 6-min walk test, short-physical performance battery, timed up-and-go test and 30-s chair-stand test. Fixed- and random-effects meta-analysis models were used to generate pooled weighted mean differences (WMDs) and 95% CIs. Heterogeneity was examined in subgroup and sensitivity analyses. Publication bias assessments were performed.ResultsA total of 17 RCTs enrolling 1418 subjects were identified. Leucine-isolated supplementation showed no effect on total lean mass (WMD = 0.03 kg, 95% CI: –0.51, 0.57, P = 0.917), handgrip strength (WMD = 1.23 kg, 95% CI: –0.58, 3.03, P = 0.183) and leg press (WMD = –1.35 kg, 95% CI: –7.46, 4.77, P = 0.666). However, leucine-combined supplementation including vitamin D showed a significant improvement in handgrip strength (WMD = 2.17 kg, 95% CI: 0.24, 4.10, P = 0.027) and gait speed (WMD = 0.03 m/s, 95% CI: 0.01, 0.05, P = 0.008).ConclusionLeucine-isolated supplementation did not improve muscle mass and strength in elderly. However, leucine-combined supplementation including vitamin D exhibited a significant benefit for muscle strength and performance including handgrip strength and gait speed in older adults. A combination of nutritional supplements would be a viable option for improving sarcopenia.

Can Nutrition Contribute to a Reduction in Sarcopenia, Frailty, and Comorbidities in a Super-Aged Society?

“…Fifteen systematic reviews We found 13 systematic reviews wherein the authors explored nutritional interventions in elderly individuals. Four systematic reviews showed the beneficial effects of leucine supplementation [42][43][44][45]. Three systematic reviews demonstrated the effect of β-hydroxyβ-methylbutyrate (HMB) on muscle mass and strength [46][47][48].…”

Nutritional Supplementation for the Prevention of Muscle Atrophy in Older People

“…A 2015 meta-analysis showed that protein fractional synthetic rate was increased in a leucine-supplemented group compared with a control group; however, no increases in lean body mass or leg lean mass were recorded 46 . A more recent meta-analysis published in 2022 of 17 RCTs consisting of 1418 participants also demonstrated that leucine-isolated supplementation does not significantly improve muscle mass or strength in older people 47 . However, those who took a leucine supplement including vitamin D showed an increase in handgrip strength and gait speed.…”

“…The mechanisms behind the enhanced effect of cotreatment remain unclear. However, it has been hypothesized that both leucine and vitamin D both inhibit muscle atrophy–related transcription factors and stimulate the mTORc pathway 47 …”

“…46 A more recent meta-analysis published in 2022 of 17 RCTs consisting of 1418 participants also demonstrated that leucine-isolated supplementation does not significantly improve muscle mass or strength in older people. 47 However, those who took a leucine supplement including vitamin D showed an increase in handgrip strength and gait speed. The mechanisms behind the enhanced effect of cotreatment remain unclear.…”

“…However, it has been hypothesized that both leucine and vitamin D both inhibit muscle atrophy-related transcription factors and stimulate the mTORc pathway. 47 The data suggest that leucine supplementation requires further investigation and that the synergistic use of leucine alongside other nutritional supplements may increase MPS, which translates to improvements in muscle mass and physical function outcomes in sarcopenic individuals (Supplementary Table 2, http://links.lww.com/NT/A35).…”