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The Effect of β-Hydroxy-β-Methyl Butyrate (HMB) upon Acute Fed-State Muscle Protein Turnover in Older Men and Women: A Randomized Double-Blind Controlled Crossover Clinical Trial.

  • 2026-04-30
  • Nutrients 18(9)
    • Kenneth Smith
    • Kenneth Smith
    • Haitham Abdullah
    • Supreeth Rudrappa
    • Amanda Gates
    • Jonathan Lewis
    • Iskandar Idris
    • Joseph J Bass
    • Hannah Crossland
    • Daniel J Wilkinson
    • Min Tian
    • Deborah S Hustead
    • Geraldine E Baggs
    • Suzette L Pereira
    • Bethan E Phillips
    • Philip J Atherton

Study Design

Type
Randomized Controlled Trial (RCT)
Sample size
n = 24
Population
24 community-dwelling older adults (68.5 ± 0.6 years; 13 men, 11 women)
Methods
randomized cross-over double-blind design to 40 g whey protein (Control) or 40 g whey protein with 3 g calcium-HMB (HMB); primed constant infusion of 13C6 phenylalanine to assess muscle protein synthesis and muscle protein breakdown
Blinding
Double-blind
Duration
3 h fed-state
  • Rigorous Journal
Background/Objectives: Anabolic resistance is thought to underlie muscle loss in sarcopenia. Here, we investigated the adjuvant role of beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, on the acute muscle anabolic response to oral protein supplementation in older adults. Methods: A total of 24 community-dwelling older adults (68.5 ± 0.6 years; 13 men, 11 women) were randomized in a cross-over double-blind design to 40 g whey protein (Control) or 40 g whey protein with 3 g calcium-HMB (HMB). Subjects received a primed constant infusion of 13C6 phenylalanine to assess muscle protein synthesis (MPS, by tracer incorporation in myofibrils) and muscle protein breakdown (MPB, via arterio-venous dilution) at baseline and post supplementation. Fasted and 3 h fed-state plasma HMB, aminoacidemia, rates of MPS, MPB, limb and muscle blood flow were measured. Results: In all subjects, both interventions displayed significant increases in MPS in response to feeding [fasted to 3 h-fed change (mean ± SEM, standard error of the mean). Males: control, +0.032 ± 0.006%.h-1; HMB, +0.023 ± 0.004%.h-1; females: control, +0.023 ± 0.006%.h-1; HMB, +0.038 ± 0.006%.h-1, p < 0.05]. In older women, the addition of HMB further enhanced the MPS response (fasted to 3 h-fed change, p = 0.0495) and area under the curve (p = 0.0364) versus protein alone. During the late-fed period, MPB significantly decreased in HMB versus control (p = 0.0298), and this was also observed when subjects were separated by sex (p = 0.0012). Conclusions: High-dose protein bolus feeding increased MPS in older adults. Surprisingly, 40 g whey did not maximize the anabolic response in older women, and HMB further increased the MPS feeding response to protein. HMB further suppressed the MPB feeding response over a longer period of time. Further work is needed to understand the apparent sexual dimorphic MPS response to high protein.

Research Insights

  • Whey Protein→Increased Muscle Protein Synthesis

    In all subjects, both interventions displayed significant increases in MPS in response to feeding [fasted to 3 h-fed change ... p < 0.05].

    Effect
    Beneficial
    Effect size
    Small
    Dose
    40 g whey protein
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