Smith · Nutrients 2026 · randomized double-blind crossover trial · n=24

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.

Level 2 - randomized trial

Individual randomized double-blind crossover clinical trial

PubMed 42124050 · doi:10.3390/nu18091449 · record verified 2026-08-26

What was done

Twenty-four community-dwelling older adults (mean age 68.5 ± 0.6 years; 13 men, 11 women) completed a randomized, double-blind crossover trial comparing 40 g whey protein alone against 40 g whey protein plus 3 g calcium-HMB. A primed constant infusion of 13C6 phenylalanine was used to assess muscle protein synthesis via myofibrillar tracer incorporation and muscle protein breakdown via arterio-venous dilution over a 3-hour fed period, alongside measurements of plasma HMB, aminoacidemia, and limb and muscle blood flow.

What was found

Both interventions significantly increased muscle protein synthesis (MPS) from baseline to 3 hours fed (p < 0.05). Fasted to 3-hour fed changes in MPS were +0.032 ± 0.006%/h for control vs +0.023 ± 0.004%/h for HMB in males, and +0.023 ± 0.006%/h for control vs +0.038 ± 0.006%/h for HMB in females. In females, HMB significantly enhanced the MPS change (p = 0.0495) and area under the curve (p = 0.0364) compared to control. During the late-fed period, muscle protein breakdown significantly decreased with HMB compared to control (p = 0.0298 overall; p = 0.0012 when separated by sex). Numerical values for breakdown rates, blood flow, and aminoacidemia were not reported in the abstract.

Why it matters

Adding HMB to a high-dose protein meal prolongs the suppression of muscle protein breakdown in older adults and may enhance the acute synthetic response specifically in older women, providing insights into nutritional strategies for sarcopenia.

Limits

The study evaluated only acute 3-hour postprandial responses in a small cohort (n = 24), which cannot directly establish long-term changes in muscle mass, strength, or physical function. The MPS elevation in females was of borderline statistical significance (p = 0.0495), and specific numerical data for breakdown and blood flow were not provided in the abstract.

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