-hydroxy--methylbutyrate (HMB) production in human subjects

RationaleHMB is produced from the amino acid leucine in the body. Studies in sheep/pigs have demonstrated that HMB production accounts for 210% of Leucine turnover, but HMB production in humans is unknown. In contrast, HMB supplementation to individuals promotes maintenance of muscle mass when subjected to muscle wasting conditions. Therefore, we hypothesize that in subjects with low muscle mass, whole body HMB production is reduced. We first developed a method to measure whole body HMB production and the conversion of Leucine to HMB in humans.MethodWe assessed the whole body production of leucine and HMB by providing a single intravenous pulse dose of L[U13C6]Leucine and [3,4, methyl13C3]HMB in human subjects in the post absorptive state and sampled blood over a 3 hour period. Plasma enrichment of [3,4, methyl13C3]HMB was determined by GC/MS/MS methods and plasma enrichment of L[U13C6]Leucine was determined by LC/MS/MS. Data are summarized as mean (SE) in mol/kg ffm/hr. Fitting of enrichment curves, ANOVA and student's ttests were done by GraphPad Prism 6.ResultsThe decay of the plasma HMB and Leucine enrichments were strictly two exponential. We determined HMB production to be 0.28 mol/kg ffm/hr and leucine turnover to be 100 mol/kg ffm/hr. Only 0.28% of the total leucine turnover is converted to HMB.ConclusionWhole body HMB production is much lower in humans than reported production in large animals.

-hydroxy--methylbutyrate (HMB) production in human subjects Conference Paper