Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism

Wilkinson, Daniel J.; Hossain, T.; Limb, Marie C.; Phillips, Bethan E.; Lund, J.; Williams, John P.; Brook, Matthew S.; Cegielski, Jessica; Philp, A.; Ashcroft, S.; Rathmacher, J. A.; Szewczyk, N. J.; Smith, K.; Atherton, Philip J.

Abstract

Background & aims: β-hydroxy-β-methylbutyrate (HMB) is purported as a key nutritional supplement for the preservation of muscle mass in health, disease and as an ergogenic aid in exercise. Of the two available forms of HMB (calcium (Ca-HMB) salt or free acid (FA-HMB)) – differences in plasma bioavailability have been reported. We previously reported that ∼3 g oral FA-HMB increased muscle protein synthesis (MPS) and reduced muscle protein breakdown (MPB). The objective of the present study was to quantify muscle protein metabolism responses to oral Ca-HMB.

Methods: Eight healthy young males received a primed constant infusion of 1,2 13C2 leucine and 2H5 phenylalanine to assess MPS (by tracer incorporation in myofibrils) and MPB (via arterio-venous (A-V) dilution) at baseline and following provision of ∼3 g of Ca-HMB; muscle anabolic (MPS) and catabolic (MPB) signalling was assessed via immunoblotting.

Results: Ca-HMB led a significant and rapid (<60 min) peak in plasma HMB concentrations (483.6 ± 14.2 μM, p < 0.0001). This rise in plasma HMB was accompanied by increases in MPS (PA: 0.046 ± 0.004%/h, CaHMB: 0.072 ± 0.004%/h, p < 0001) and suppressions in MPB (PA: 7.6 ± 1.2 μmol Phe per leg min−1, Ca-HMB: 5.2 ± 0.8 μmol Phe per leg min−1, p < 0.01). Increases in the phosphorylation of mTORc1 substrates i.e. p70S6K1 and RPS6 were also observed, with no changes detected in the MPB targets measured.

Conclusions: These findings support the pro-anabolic properties of HMB via mTORc1, and show that despite proposed differences in bioavailability, Ca-HMB provides a comparable stimulation to MPS and suppression of MPB, to FA-HMB, further supporting its use as a pharmaconutrient in the modulation of muscle mass.

Citation

Wilkinson, D. J., Hossain, T., Limb, M. C., Phillips, B. E., Lund, J., Williams, J. P., Brook, M. S., Cegielski, J., Philp, A., Ashcroft, S., Rathmacher, J. A., Szewczyk, N. J., Smith, K., & Atherton, P. J. (2018). Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism. Clinical Nutrition, 37(6), 2068-2075. https://doi.org/10.1016/j.clnu.2017.09.024

• Journal Article Type: Article
• Acceptance Date: Sep 29, 2017
• Online Publication Date: Oct 6, 2017
• Publication Date: Dec 1, 2018
• Deposit Date: Nov 8, 2017
• Publicly Available Date: Nov 8, 2017
• Journal: Clinical Nutrition
• Print ISSN: 0261-5614
• Electronic ISSN: 1532-1983
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 37
• Issue: 6
• Pages: 2068-2075
• DOI: https://doi.org/10.1016/j.clnu.2017.09.024
• Keywords: β-Hydroxy-β-methylbutyrate; Skeletal muscle; Protein metabolism; Anabolism
• Public URL: https://nottingham-repository.worktribe.com/output/886710
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0261561417313560
• Additional Information: This article is maintained by: Elsevier; Article Title: Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism; Journal Title: Clinical Nutrition; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.clnu.2017.09.024; Content Type: article; Copyright: © 2017 The Authors. Published by Elsevier Ltd.
• Contract Date: Nov 8, 2017