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High-dose leucine supplementation does not prevent muscle atrophy or strength loss over 7 days of immobilization in healthy young males


BACKGROUND: Unavoidable periods of disuse lead to muscle atrophy and functional decline. Preventing such declines can reduce the risk of re-injury and improve recovery of normal physiological functioning. OBJECTIVES: We aimed to determine the effectiveness of high-dose leucine supplementation on muscle morphology and strength during 7 d of unilateral lower-limb immobilization, and the role of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis in disuse atrophy. METHODS: Sixteen healthy males (mean +/- SEM age: 23 +/- 1 y) underwent 7 d of unilateral lower-limb immobilization, with thrice-daily leucine (LEU; n = 8) or placebo (PLA; n = 8) supplementation (15 g/d). Before and after immobilization, muscle strength and compartmental tissue composition were assessed. A primed continuous infusion of l-[ring-13C6]-phenylalanine with serial muscle biopsies was used to determine postabsorptive and postprandial (20 g milk protein) MyoPS and MitoPS, fiber morphology, markers of protein turnover, and mitochondrial function between the control leg (CTL) and the immobilized leg (IMB). RESULTS: Leg fat-free mass was reduced in IMB (mean +/- SEM: -3.6% +/- 0.5%; P = 0.030) but not CTL with no difference between supplementation groups. Isometric knee extensor strength declined to a greater extent in IMB (-27.9% +/- 4.4%) than in CTL (-14.3% +/- 4.4%; P = 0.043) with no difference between groups. In response to 20 g milk protein, postprandial MyoPS rates were significantly lower in IMB than in CTL (-22% +/- 4%; P < 0.01) in both LEU and PLA. Postabsorptive MyoPS rates did not differ between legs or groups. Postabsorptive MitoPS rates were significantly lower in IMB than in CTL (-14% +/- 5%; P < 0.01) and postprandial MitoPS rates significantly declined in response to 20 g milk protein ingestion (CTL: -10% +/- 8%; IMB: -15% +/- 10%; P = 0.039), with no differences between legs or groups. There were no significant differences in measures of mitochondrial respiration between legs, but peroxisome proliferator-activated receptor gamma coactivator 1-alpha and oxidative phosphorylation complex II and III were significantly lower in IMB than in CTL (P < 0.05), with no differences between groups. CONCLUSIONS: High-dose leucine supplementation (15 g/d) does not appear to attenuate any functional declines associated with 7 d of limb immobilization in young, healthy males.This trial was registered at as NCT03762278.

Type Journal
ISBN 1938-3207 (Electronic) 0002-9165 (Linking)
Authors Edwards, S. J.; Smeuninx, B.; McKendry, J.; Nishimura, Y.; Luo, D.; Marshall, R. N.; Perkins, M.; Ramsay, J.; Joanisse, S.; Philp, A.; Breen, L.
Responsible Garvan Author Dr Andy Philp
Published Date 2020-11-30
Published Volume 112
Published Issue 5
Published Pages 1368-1381
Status Published in-print
DOI 10.1093/ajcn/nqaa229
URL link to publisher's version