Failure of infused beta-hydroxybutyrate to decrease proteolysis in man.
Level 3 - non-randomized controlled study
Non-randomized interventional human metabolic tracer study with a control group
PubMed 6298041 · doi:10.2337/diab.32.3.197
What was done
Six healthy postabsorptive volunteers received a 3-hour intravenous infusion of Na-beta-hydroxybutyrate. Isotope tracers ([3-3H]glucose, L-[6,6,6-2H3]leucine, [2,3,3,3-2H4]alanine, and [15N]leucine) were used to trace the kinetics of glucose, alanine, and leucine carbon and nitrogen, including leucine nitrogen transfer to alanine. To control for the confounding alkalemia from the sodium salt, four additional subjects were infused with NaHCO3.
What was found
During Na-beta-hydroxybutyrate infusion, plasma alanine decreased (P < 0.05) and plasma leucine increased (P < 0.05). Alanine rate of appearance increased from 5.3 ± 0.3 to 7.8 ± 0.6 µmol/kg·min, but alanine disappearance increased slightly more, explaining the lower plasma alanine concentration. Leucine nitrogen flux and the rate and percent of leucine nitrogen transferred to alanine increased, while leucine carbon flux remained unchanged. In the NaHCO3 control group, alkalemia did not affect leucine carbon or nitrogen flux or alanine appearance, but increased alanine disappearance and decreased plasma alanine concentration.
Why it matters
These findings refute the concept that ketone bodies directly suppress whole-body proteolysis in postabsorptive humans, showing instead that acute hyperketonemia alters amino acid clearance and transamination without reducing protein breakdown.
Limits
The sample size is very small (n = 6 intervention, n = 4 control). The infusion was limited to 3 hours in healthy postabsorptive subjects, which does not address prolonged fasting, chronic ketosis, or pathological catabolic states.
Cited by
- supports Intravenous infusion of beta-hydroxybutyrate in humans causes a sharp decrease in circulating alanine and preserves or elevates branched-chain amino acids such as leucine.