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Failure of infused beta-hydroxybutyrate to decrease proteolysis in man.

J M Miles, S L Nissen, R A Rizza

|March 1, 1983

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Ketone bodies may not spare protein as initially thought. Studies show increased alanine disappearance, not decreased protein breakdown, during ketone infusions in humans.

Area of Science:

Metabolic studies
Human physiology

Background:

Ketone bodies are proposed to have a protein-sparing effect.
Evidence suggests decreased plasma alanine and urinary nitrogen during ketone infusion.

Purpose of the Study:

To investigate the protein-sparing hypothesis of ketone bodies.
To determine if hyperketonemia reduces proteolysis in postabsorptive individuals.

Main Methods:

Infusion of sodium beta-hydroxybutyrate in six volunteers.
Tracer studies using isotopes to measure glucose, leucine, and alanine metabolism.
Assessment of nitrogen flux and transfer using 15N-leucine.
Control infusion of sodium bicarbonate to assess alkalemia effects.

Main Results:

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Plasma alanine decreased, while plasma leucine increased during ketone infusion.
Alanine appearance rate increased, but disappearance rate increased more, causing the plasma decrease.
Leucine nitrogen flux and transfer to alanine increased; leucine carbon flux remained unchanged.
Alkalemia alone did not affect leucine flux but increased alanine disappearance.

Conclusions:

Hyperketonemia does not appear to decrease proteolysis in postabsorptive humans.
The observed decrease in plasma alanine is likely due to increased catabolism, not reduced protein breakdown.
Alkalemia contributes to decreased plasma alanine by enhancing its clearance.