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

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 bio...

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Main Authors: 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, Nathaniel J., Smith, K., Atherton, Philip J.
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Published: Elsevier 2017
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Online Access:https://eprints.nottingham.ac.uk/47970/
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author 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, Nathaniel J.
Smith, K.
Atherton, Philip J.
author_facet 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, Nathaniel J.
Smith, K.
Atherton, Philip J.
author_sort Wilkinson, Daniel J.
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-479702024-08-15T15:24:21Z https://eprints.nottingham.ac.uk/47970/ 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, Nathaniel J. Smith, K. Atherton, Philip J. 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. Elsevier 2017-10-06 Article PeerReviewed 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, Nathaniel J., Smith, K. and Atherton, Philip J. (2017) Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism. Clinical Nutrition . ISSN 1532-1983 (In Press) β-Hydroxy-β-methylbutyrate; Skeletal muscle; Protein metabolism; Anabolism http://www.sciencedirect.com/science/article/pii/S0261561417313560?via%3Dihub doi:10.1016/j.clnu.2017.09.024 doi:10.1016/j.clnu.2017.09.024
spellingShingle β-Hydroxy-β-methylbutyrate; Skeletal muscle; Protein metabolism; Anabolism
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, Nathaniel J.
Smith, K.
Atherton, Philip J.
Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism
title Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism
title_full Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism
title_fullStr Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism
title_full_unstemmed Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism
title_short Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism
title_sort impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism
topic β-Hydroxy-β-methylbutyrate; Skeletal muscle; Protein metabolism; Anabolism
url https://eprints.nottingham.ac.uk/47970/
https://eprints.nottingham.ac.uk/47970/
https://eprints.nottingham.ac.uk/47970/