Leucine partially protects muscle mass and function during bed rest in middle-aged adults

Abstract

Background: Physical inactivity triggers a rapid loss of muscle mass and function in older adults. Middle-aged adults show few phenotypic signs of aging yet may be more susceptible to inactivity than younger adults.

Objective: The aim was to determine whether leucine, a stimulator of translation initiation and skeletal muscle protein synthesis (MPS), can protect skeletal muscle health during bed rest.

Design: We used a randomized, double-blind, placebo-controlled trial to assess changes in skeletal MPS, cellular signaling, body composition, and skeletal muscle function in middle-aged adults (n = 19; age ± SEM: 52 ± 1 y) in response to leucine supplementation (LEU group: 0.06 g ∙ kg(-1) ∙ meal(-1)) or an alanine control (CON group) during 14 d of bed rest.

Results: Bed rest decreased postabsorptive MPS by 30% ± 9% (CON group) and by 10% ± 10% (LEU group) (main effect for time, P < 0.05), but no differences between groups with respect to pre-post changes (group × time interactions) were detected for MPS or cell signaling. Leucine protected knee extensor peak torque (CON compared with LEU group: -15% ± 2% and -7% ± 3%; group × time interaction, P < 0.05) and endurance (CON compared with LEU: -14% ± 3% and -2% ± 4%; group × time interaction, P < 0.05), prevented an increase in body fat percentage (group × time interaction, P < 0.05), and reduced whole-body lean mass loss after 7 d (CON compared with LEU: -1.5 ± 0.3 and -0.8 ± 0.3 kg; group × time interaction, P < 0.05) but not 14 d (CON compared with LEU: -1.5 ± 0.3 and -1.0 ± 0.3 kg) of bed rest. Leucine also maintained muscle quality (peak torque/kg leg lean mass) after 14 d of bed-rest inactivity (CON compared with LEU: -9% ± 2% and +1% ± 3%; group × time interaction, P < 0.05).

Conclusions: Bed rest has a profoundly negative effect on muscle metabolism, mass, and function in middle-aged adults. Leucine supplementation may partially protect muscle health during relatively brief periods of physical inactivity. This trial was registered at clinicaltrials.gov as NCT00968344.

Keywords: atrophy; dietary supplementation; nutrition; physical inactivity; skeletal muscle protein synthesis.

© 2016 American Society for Nutrition.

Figures

FIGURE 1

Study timeline. The pre–bed-rest phase consisted of a 3-d inpatient stay during which subjects completed baseline testing of dependent measures and consumed a controlled diet. During the 14-d bed-rest phase, subjects continued to consume the research diet in addition to either a leucine (experimental) or alanine (control) supplement with each of the 3 daily meals. Dependent measures were reassessed post–bed rest; body composition was also measured after 7 d of bed rest. Control group, n = 9; leucine-supplemented group, n = 10. BR, bed rest; LEU, leucine.

FIGURE 2

Metabolic study timeline. Postabsorptive and postprandial cell signaling were determined from biopsy samples 1 and 3, respectively. Postabsorptive FSR was calculated by using biopsy samples 1 and 2; FSR in the postprandial state was determined by using biopsy samples 2 and 4. Control group, n = 9; leucine-supplemented group, n = 10. Bx, muscle biopsy; EAA, essential amino acid; FSR, fractional synthesis rate.

FIGURE 3

Plasma enrichment of l-[ring-13C6]phenylalanine (tracer:tracee ratio) during metabolic studies; enrichments for pre– and post–bed-rest metabolic studies were averaged within groups. Values are means ± SEMs; CON, n = 9; LEU, n = 10. CON, control group; LEU, leucine-supplemented group.