Effect of ketone infusions on amino acid and nitrogen metabolism in man

Abstract

To evaluate the role of hyperketonemia in the hypoalaninemia and decreased protein catabolism of prolonged starvation, Na DL β hydroxybutyrate was administered as a primed continuous 3-6 hr infusion in nonobese subjects and in obese subjects in the postabsorptive state and after 3 days and 3-5.5 wk of starvation. An additional obese group received 12 h ketone infusions on 2 consecutive days after 5-10 wk of fasting. The ketone infusion in obese and nonobese subjects studied in the post absorptive state resulted in total blood ketone acid levels of 1.1-1.2 mM, a 5-15 mg/100 ml decrease in plasma glucose, and unchanged levels of insulin, glucagon, lactate, and pyruvate. Plasma alanine fell by 21% (P<0.001) in 3 h. In contrast, other amino acids were stable or varied by less than 10%. Infusions lasting 6 h reduced plasma alanine by 37%, reaching levels comparable to those observed in prolonged starvation. Equimolar infusions of NaCl and/or administration of NaHCO3 failed to alter plasma alanine levels. During prolonged fasting, plasma alanine, which had fallen by 40% below prefast levels, fell an additional 30% in response to the ketone infusion. In association with repeated prolonged (12 h) infusions in subjects fasted 5-10 wk, urinary nitrogen excretion fell by 30%, returning to base line after cessation of the infusions and paralleling the changes in plasma alanine. Ketone infusions resulted in two to fourfold greater increments in blood ketone acids in fasted as compared to postabsorptive subjects. It is concluded that increased blood ketone acid levels induced by infusions of Na DLβ hydroxybutyrate result in hypoalaninemia and in nitrogen conservation in starvation. These data suggest that hyperketonemia may be a contributory factor in the decreased availability of circulating alanine and reduction in protein catabolism characteristic of prolonged fasting.