Impact of hydroxy-methylbutyrate (HMB) on muscle loss and protein metabolism in critically ill patients: A RCT Academic Article uri icon


  • Purpose

    Muscle wasting deteriorates life quality after critical illness and increases mortality. Wasting starts upon admission to intensive care unit (ICU). We aimed to determine whether β-hydroxy-β-methylbutyrate (HMB), a metabolite of leucine, can attenuate this process.


    Prospective randomized, placebo-controlled double blind trial.

    Inclusion criteria

    ICU patients depending on mechanical ventilation on day 3 having a functional gastrointestinal tract. They were randomized to HMB (3 g/day) or placebo (maltodextrin) from day 4 on for 30 days.

    Primary outcome

    magnitude of loss of skeletal muscle area (SMA) of the quadriceps femoris measured by ultrasound at days 4 and 15.

    Secondary outcomes

    body composition, change in protein metabolism assessed by amino acids tracer pulse, and global health at 60 days. Data are mean [95% CI]. Statistics by ANCOVA with correction for confounders sex, age and/or BMI.


    Thirty patients completed the trial, aged 65 [59, 71] years, SAPS2 score 48 [43, 52] and SOFA 8.5 [7.4, 9.7]. The loss of total SMA was 11% between days 4 and 15 (p < 0.001), but not different between the groups (p = 0.86). In the HMB group, net protein breakdown (Δ Estimate HMB-Placebo: -153 [-242, -63]; p = 0.0021) and production of several amino acid was significantly reduced, while phase angle increased more (0.66 [0.09, 1.24]; p = 0.0247), and SF-12 global health improved more (Δ Estimate HMB-Placebo: 27.39 [1.594, 53.19], p = 0.04).


    HMB treatment did not significantly reduce muscle wasting over 10 days of observation (primary endpoint), but resulted in significantly improved amino acid metabolism, reduced net protein breakdown, a higher phase angle and better global health. CLINICALTRIALS.

    Gov identifier


published proceedings

  • Clinical Nutrition

altmetric score

  • 13.95

author list (cited authors)

  • Viana, M. V., Becce, F., Pantet, O., Schmidt, S., Bagnoud, G., Thaden, J. J., ... Berger, M. M.

citation count

  • 6

complete list of authors

  • Viana, Marina V||Becce, Fabio||Pantet, Olivier||Schmidt, Sabine||Bagnoud, Géraldine||Thaden, John J||Ten Have, Gabriella AM||Engelen, Mariëlle PKJ||Voidey, Aline||Deutz, Nicolaas EP||Berger, Mette M

publication date

  • August 2021