Effect of β-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans

Abstract

Because intravenous infusion of β-hydroxybutyrate (β-OHB) has been reported to decrease urinary nitrogen excretion, we investigated in vivo metabolism of leucine, an essential amino acid, using L-[1-13C]leucine as a tracer during β-OHB infusion. Leucine flux during β-OHB infusion did not differ from leucine flux during normal saline infusion in nine normal subjects, whereas leucine oxidation decreased 18-41% (mean = 30%) from 18.1 ± 1.1 μmol·kg-1·h-1 (P < 0.01), and incorporation of leucine into skeletal muscle protein increased 5-17% (mean = 10%) from 0.048 + 0.003%/h (P < 0.02). Since blood pH during β-OHB infusion was higher than the pH during saline infusion, we performed separate experiments to study the effect of increased blood pH on leucine kinetics by infusing sodium bicarbonate intravenously. Blood pH during sodium bicarbonate infusion was similar to that observed during the β-OHB infusion, but bicarbonate infusion had no effect on leucine flux or leucine oxidation. We conclude that β-OHB decreases leucine oxidation and promotes protein synthesis in human beings.