Investigating effects of sodium beta‐hydroxybutyrate on metabolism in placebo‐controlled, bilaterally infused human leg with focus on skeletal muscle protein dynamics

Systemic administration of beta‐hydroxybutyrate (BHB) decreases whole‐body protein oxidation and muscle protein breakdown in humans. We aimed to determine any direct effect of BHB on skeletal muscle protein turnover when administered locally in the femoral artery. Paired design with each subject being investigated on one single occasion with one leg being infused with BHB and the opposing leg acting as a control. We studied 10 healthy male volunteers once with bilateral femoral vein and artery catheters. One artery was perfused with saline (Placebo) and one with sodium‐BHB. Labelled phenylalanine and palmitate were used to assess local leg fluxes. Femoral vein concentrations of BHB were significantly higher in the intervention leg (3.4 (3.2, 3.6) mM) compared with the placebo‐controlled leg (1.9 (1.8, 2.1) mM) with a peak difference of 1.4 (1.1, 1.7) mM, p < 0.0005. Net loss of phenylalanine for BHB vs Placebo −6.7(−10.8, −2.7) nmol/min vs −8.7(−13.8, −3.7) nmol/min, p = 0.52. Palmitate flux and arterio‐venous difference of glucose did not differ between legs. Under these experimental conditions, we failed to observe the direct effects of BHB on skeletal muscle protein turnover. This may relate to a combination of high concentrations of BHB (close to 2 mM) imposed systemically by spillover leading to high BHB concentrations in the saline‐infused leg and a lack of major differences in concentration gradients between the two sides—implying that observations were made on the upper part of the dose–response curve for BHB and the relatively small number of subjects studied.