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. 2018 Dec;37(6 Pt A):2068-2075.
doi: 10.1016/j.clnu.2017.09.024. Epub 2017 Oct 6.

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

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

D J Wilkinson et al. Clin Nutr. 2018 Dec.

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.

Keywords: Anabolism; Protein metabolism; Skeletal muscle; β-Hydroxy-β-methylbutyrate.

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Figures

Fig. 1
Fig. 1
Study schematic for assessing the effects of Ca-HMB on human skeletal muscle metabolism.
Fig. 2
Fig. 2
A) Bioavailability of HMB following oral provision of Ca-HMB measured by plasma HMB concentrations. ****Significantly different from fasted, p < 0.0001. Effects of Ca-HMB on B) human skeletal muscle myofibrillar protein synthesis (FSR) and C) muscle protein breakdown. Significant difference from post-absorptive (PA), ***p < 0.001, **p < 0.01.
Fig. 3
Fig. 3
Signalling responses of A) p-p70S6K1Thr389, B) p-RPS6Ser240/244, C) p-AktSer308, D) p-AktThr473, E) Total MuRF1 and F) Total Mafbx to oral provision of CaHMB. Significant difference from post-absorptive (PA), *p < 0.05.
Fig. 4
Fig. 4
Summary comparison of anabolic and catabolic responses to oral provision of 3.42 g of Ca-HMB (equivalent to 2.74 g of FA-HMB) and 2.42 g FA-HMB (FA-HMB data taken from Wilkinson et al. [8]). Both forms of HMB result in an equivalent stimulation of MPS and suppression of MPB (* represents significant change from postabsorptive) highlighting potent (and possibly maximal) anabolic effects from a single acute oral dose of HMB independent of calcium or free-acid form.

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