Systemic, cerebral and skeletal muscle ketone body and energy metabolism during acute hyper-D-β-hydroxybutyratemia in post-absorptive healthy males.
Level 4 - case-series / case-control
Uncontrolled acute experimental physiological infusion trial
PubMed 25415176 · doi:10.1210/jc.2014-2608
What was done
Six healthy post-absorptive males underwent an acute physiological infusion study. Following basal measurements, participants received graded infusions of D-β-hydroxybutyrate (HOB) across three consecutive 1-hour periods targeting 3-, 6-, and 12-fold increases in blood HOB concentration. Systemic, cerebral, and skeletal muscle HOB kinetics, oxidation, glucose turnover, and lipolysis were measured using combined arterial, internal jugular venous, and femoral venous catheter sampling alongside stable isotope infusions of labeled HOB, glucose, and glycerol.
What was found
Increasing blood HOB from basal 160 μmol/L to 450 μmol/L caused a 14 ± 2% reduction (P = .03) in the rate of glucose appearance and a 37 ± 4% decrease (P = .03) in lipolysis, with no changes in circulating insulin or glucagon. Endogenous HOB appearance was suppressed dose-dependently, reaching complete inhibition at the highest concentration (1.7 mmol/L). Cerebral HOB uptake and subsequent oxidation showed a linear relationship with arterial HOB concentration, whereas resting skeletal muscle HOB uptake demonstrated saturation kinetics.
Why it matters
The findings demonstrate that modest physiological increases in ketone levels acutely downregulate endogenous glucose production and lipolysis independently of insulin or glucagon, and confirm that the human brain utilizes and oxidizes ketones in direct proportion to arterial availability during acute elevation.
Limits
The study had a very small sample size (n = 6) and included exclusively healthy, post-absorptive males. It was an uncontrolled, non-randomized single trial lacking a time-matched vehicle or sham control. Interventions were brief (1-hour stages), precluding evaluation of chronic metabolic adaptations or direct therapeutic efficacy in clinical populations.
Cited by
- supports The brain metabolizes beta-hydroxybutyrate for energy in a dose-dependent manner based on circulating levels.