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

Research output: Contribution to journalArticlepeer-review


  • Sophie J Edwards
  • James Mckendry
  • Yusuke Nishimura
  • Dan Luo
  • Ryan N Marshall
  • Molly Perkins
  • Jill Ramsay
  • Sophie Joanisse
  • Andrew Philp

External organisations

  • School of Sport
  • Department of Kinesiology, University of Waterloo, Canada
  • McMaster University
  • Population Health Research Institute, Hamilton Health Sciences/McMaster University, Hamilton, Canada.
  • Transformative Pathology, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
  • School of Sport, Exercise and Health Sciences
  • University of Exeter
  • Garvan Institute of Medical Research
  • Medical Research Council-Arthritis Research UK Centre for Musculoskeletal Ageing Research


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 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.

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 clinicaltrials.gov as NCT03762278.

Bibliographic note

Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.


Original languageEnglish
Pages (from-to)1368-1381
Number of pages14
JournalThe American journal of clinical nutrition
Issue number5
Publication statusPublished - 11 Nov 2020