HMB attenuates muscle loss during sustained energy deficit induced by calorie restriction and endurance exercise

Metabolism. 2013 Dec;62(12):1718-29. doi: 10.1016/j.metabol.2013.06.005. Epub 2013 Jul 20.


Objective: To investigate the efficacy and underlying mechanisms of β-hydroxy-β-methylbutyrate (HMB) on body composition, muscle mass and physical performance under catabolic versus normal training conditions.

Materials/methods: Mice were divided into four groups (n=10/group): (1) ALT=ad libitum+trained (1 h/d for 3 d/wk); (2) ALTH=ALT+HMB (0.5 g/kg BW/d); (3) C=calorie restricted (-30%)+trained (6 h/d, 6 d/wk); and (4) CH=C+HMB. Repeated in vivo assessments included body composition, grip strength and sensorimotor coordination before and after the experimental protocol, while in vitro analyses included muscle wet weights, expression of selected genes and proteins regulating muscle mass, and myofiber cross-sectional area. ANOVAs were used with significance set at p<0.05.

Results: ALTH had greater lean mass than ALT and sensorimotor function increased in ALTH, but decreased in ALT under normal training conditions. Grip strength decreased only in C, but was maintained in CH. Gastrocnemius mass and myofiber CSA were greater in CH than C following catabolic conditions. Gastrocnemius atrogin-1 mRNA expression was elevated in C but not in CH compared to all other groups whereas atrogin-1 protein levels showed no significant changes.

Conclusion: HMB improves body composition and sensorimotor function during normal training and attenuates muscle mass and strength loss during catabolic conditions.

Keywords: ALT; ALTH; B; BH; Body composition; C; CH; CSA; Catabolic; DXA; Dual Energy X-ray Absorptiometry; Functionality; GAPDH; HMB; LBM; Mice; NHMFL; National High Magnetic Field Laboratory; Protein degradation; RT-PCR; Reverse Transcription Polymerase Chain Reaction; SUSOPS; TB; ad libitum-trained; ad libitum-trained+HMB; baseline; baseline+HMB; caloric restricted+trained; caloric restricted+trained+HMB; cross-sectional area; glyceraldehydes 3-phosphate dehydrogenase; lean body mass; sustained operations; true baseline; β-hydroxy-β-methylbutyrate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anatomy, Cross-Sectional
  • Animals
  • Blotting, Western
  • Body Composition / physiology
  • Caloric Restriction*
  • Diet
  • Energy Metabolism / drug effects*
  • Energy Metabolism / physiology*
  • Hand Strength / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria, Muscle / drug effects
  • Mitochondria, Muscle / physiology
  • Muscle Fibers, Skeletal / physiology
  • Muscle Proteins / metabolism
  • Muscle Strength / physiology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiology*
  • Neural Conduction / physiology
  • Organ Size / physiology
  • Physical Conditioning, Animal / physiology*
  • Physical Endurance / physiology*
  • Real-Time Polymerase Chain Reaction
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / metabolism
  • Valerates / pharmacology*


  • Muscle Proteins
  • Tripartite Motif Proteins
  • Valerates
  • beta-hydroxyisovaleric acid
  • Fbxo32 protein, rat
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, mouse
  • Ubiquitin-Protein Ligases