Does β-hydroxy-β-methylbutyrate (HMB) have an anti-inflammatory impact in critically ill patients? A secondary post hoc analysis of an RCT.

Abstract / Summary

Beta-hydroxy-beta-methylbutyrate (HMB), a natural breakdown product of the amino acid leucine, has been shown to increase protein synthesis in human skeletal muscle. After demonstrating in a randomised 10-day supplementation trial using isotopes, a significant reduction of net protein breakdown in critically ill patients, this post-hoc study aimed to investigate the global, extra-, and intracellular protein synthesis pathways impacted by HMB, and its influence on the inflammatory response. This secondary post-hoc analysis used data from the previously published randomized trial, where critically ill patients were supplied with 3 g of HMB/day or placebo for at least 10 days. The study procedures were conducted in the postabsorptive state on days 4 and 15 after ICU admission. Blood analysis included cytokines (by Luminex), C-reactive protein (CRP), amino acids (AA), urea and creatinine. Amino acid whole body productions and plasma concentrations were measured after pulse administrations of an 8 mL solution containing 18 stable AA tracers. Data are presented as means [95%CI]. Altogether 37 patients were included (aged 65 [56, 74] years, SAPS2 48 [40, 52], and APACHEII 23 [19, 26]): baseline characteristics did not differ between the groups. Among the 37 measured cytokines, most declined by day 15, except for some specific growth factors. Twelve cytokines differed significantly between groups post-intervention, with levels being higher in HMB group (including 7 proinflammatory cytokines) (p < 0.05). Whole body production of AA and extracellular pool sizes did not differ significantly by day 15. In the HMB group (vs. placebo), the intracellular pool sizes of citrulline, glutamine, HMB, KMV (α-keto-β-methylvaleric acid), taurine, and tau-methyhistidine increased and were significantly higher post-intervention. Taurine production increased significantly and similarly in both groups (p < 0.05) but glutamine and HMB production increased significantly more in the HMB group. In parallel, the urea to creatinine ratio decreased significantly (125 vs 181, p = 0.002) by day 15 in the HMB group. The present study shows that HMB supplementation is associated with a different inflammatory pattern, suggesting a more efficient immune response. Furthermore, HMB has a significant impact on intracellular synthesis of selected AA, particularly glutamine. (NCT03628365: https://clinicaltrials.gov/ct2/show/NCT03628365).

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