Leucine supplementation does not attenuate the decline in daily muscle protein synthesis rates or preserve leg muscle mass during leg immobilization in young or older adults: a double-blind randomized trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 41580240 · doi:10.1016/j.ajcnut.2026.101205
What was done
Forty-eight recreationally active adults—24 young (23 ± 4 y) and 24 older (69 ± 4 y), with equal sex distribution—underwent 3 days of unilateral knee immobilization via full leg casting. Participants were randomized in a double-blind, parallel-group design to receive either 5 g of leucine (LEU) or an energy-matched carbohydrate placebo (PLA) three times daily with main meals. Quadriceps cross-sectional area (CSA) was measured before and after immobilization in both the immobilized (IM) and non-immobilized (NO-IM) legs using computed tomography. Daily muscle protein synthesis (MPS) rates were determined in both legs using deuterated water (2H2O) coupled with saliva, blood, and muscle biopsy sampling.
What was found
Immobilization reduced daily MPS rates by ~15% in young adults (1.28 ± 0.29 vs 1.50 ± 0.26 %/d, P < 0.001) and ~23% in older adults (1.10 ± 0.16 vs 1.46 ± 0.28 %/d, P < 0.001). Leucine had no effect on MPS compared to placebo in either young (P = 0.932) or older adults (P = 0.742). Quadriceps CSA in the IM leg decreased by ~1.2% in young (7162 ± 1148 to 7076 ± 1129 mm²) and ~1.1% in older adults (5813 ± 1092 to 5750 ± 1096 mm²; P < 0.001 for both), with no difference between LEU and PLA (P = 0.374 for young, P = 0.998 for older). Older adults had lower IM leg MPS rates than young adults (difference: -0.18 %/d [95% CI: -0.31, -0.04], P = 0.013), though CSA loss did not differ significantly by age (P > 0.05).
Why it matters
Despite leucine's established role as an anabolic trigger, mealtime leucine supplementation does not protect against disuse-induced declines in daily muscle protein synthesis or acute muscle mass loss in healthy adults.
Limits
The immobilization period was brief (3 days), leaving longer-term disuse effects unmeasured. Group sizes were modest (12 participants per treatment arm per age group). The study evaluated only healthy, recreationally active participants rather than clinical populations, and tested a single dose and timing strategy (5 g with meals).
Cited by
- supports Skeletal muscle protein turns over at a rate of 1% to 2% per day, renewing completely in approximately 50 to 100 days.