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

• Published in: The American journal of clinical nutrition 2020-11, Vol.112 (5), p.1368-1381
• Main Authors: Edwards, Sophie J, Smeuninx, Benoit, Mckendry, James, Nishimura, Yusuke, Luo, Dan, Marshall, Ryan N, Perkins, Molly, Ramsay, Jill, Joanisse, Sophie, Philp, Andrew, Breen, Leigh
• Format: Article
• Language: English
• Subjects: amino acids; Atrophy; Cytotoxicity; Dietary Supplements; disuse; Dose-Response Relationship, Drug; Double-Blind Method; Fat-free body mass; Health risks; Humans; Immobilization; Ingestion; Injury prevention; Leg; Legs; Leucine; Leucine - administration & dosage; Leucine - pharmacology; Lymphocytes T; Male; Males; Milk; Mitochondria; Morphology; Muscle contraction; Muscle strength; Muscle Strength - drug effects; Muscular Atrophy - prevention & control; Oxidative phosphorylation; Phenylalanine; Phosphorylation; Protein biosynthesis; Protein synthesis; Protein turnover; Proteins; Risk reduction; skeletal muscle; Supplements; Young Adult
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1093/ajcn/nqaa229

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. 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. 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). 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 γ coactivator 1-α and oxidative phosphorylation complex II and III were significantly lower in IMB than in CTL (P < 0.05), with no differences between groups. 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 clinicaltrials.gov as NCT03762278. ▪