Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans.
Level 3 - non-randomized controlled study
Controlled within-subject physiological infusion study without stated randomization
PubMed 3392207 · doi:10.1172/JCI113570
What was done
In nine normal subjects, researchers assessed in vivo leucine metabolism using an L-[1-13C]leucine tracer during intravenous beta-hydroxybutyrate (beta-OHB) infusion compared to normal saline infusion. To isolate the effect of increased blood pH observed during beta-OHB infusion, separate experiments tested leucine kinetics during intravenous sodium bicarbonate infusion.
What was found
Leucine flux during beta-OHB infusion did not differ from normal saline infusion. Leucine oxidation decreased 18-41% (mean = 30%) from 18.1 +/- 1.1 mumol.kg-1.h-1 (P < 0.01). Skeletal muscle fractional protein synthesis increased 5-17% (mean = 10%) from 0.048 +/- 0.003%/h (P < 0.02). Sodium bicarbonate infusion raised blood pH similarly to beta-OHB but had no effect on leucine flux or leucine oxidation.
Why it matters
This study provides mechanistic human evidence that beta-hydroxybutyrate directly suppresses essential amino acid oxidation and promotes muscle protein synthesis, independent of changes in systemic pH.
Limits
The study had a very small sample size (n = 9 for the primary experiment; sample size for bicarbonate controls was not stated). It assessed only acute physiological effects of intravenous infusion in healthy individuals, leaving long-term outcomes and effects in catabolic disease states unmeasured.
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