Impact of β−hydroxy-β−methylbutyrate (HMB) on muscle loss and protein metabolism in critically ill patients: A RCT

Abstract

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 bÀhydroxy-bÀmethylbutyrate (HMB), a metabolite of leucine, can attenuate this process.Methods: 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. Results: 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 ¼ 0.86). In the HMB group, net protein breakdown (D Estimate HMB-Placebo: À153 [-242, À63]; p ¼ 0.0021) and production of several amino acid was significantly reduced, while phase angle increased more (0.66 [0.09, 1.24]; p ¼ 0.0247), and SF-12 global health improved more 53.19], p ¼ 0.04). Conclusion: 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: NCT03628365.

Muscle size, strength, and physical function in response to augmented calorie delivery: A TARGET sub-study

“…Two small RCTs report a positive effect of protein dose on attenuating muscle; in 119 patients, higher intravenous doses of protein showed greater amelioration of ultrasound-derived muscle loss and a trend towards improved handgrip strength (19), and in 60 patients an augmented calorie and protein intervention attenuated muscle loss by ICU discharge (38). Meanwhile, more recent studies have reported no effect on muscle size using an β-Hydroxy β-methylbutyric acid (HMB) intervention (39,40) or continuous vs intermittent EN (41). The role of protein dose on muscle size in critical illness needs further investigation.…”

A guide to enteral nutrition in intensive care units: 10 expert tips for the daily practice

“…Some potential alternatives include the addition of the leucine metabolite HMB (hydroxy methyl butyrate) to improve amino acid metabolism and reduce net protein breakdown [ 92 ].…”

Nutrition before, during and after critical illness

“…It seems unusual that in other areas of critical care, patients' physiological parameters are so closely monitored and treatment titrated to actual measurements (for example mean arterial pressure) but not for nutrition. Promising improvements have been shown in meta-analyses or small studies trying to provide nutrition in a more individualised and personalised approach, including the use of glycemiccontrol EN to improve blood glucose control and lower insulin use, an attempt to find differences in metabolic profile according to energy delivery using metabolomics, a combination of high protein intake and early exercise on functional outcomes, investigation of beta-hydroxy-beta-methylbutyrate compared to placebo and the attenuation of muscle wasting [21][22][23][24][25]. Although not providing definitive answers as yet, this work indicates that more thought is being paid to how individualised and personalised nutrition might benefit particular patients.…”