[2,4-13 C2 ]-beta-Hydroxybutyrate metabolism in human brain

J Cereb Blood Flow Metab. 2002 Jul;22(7):890-8. doi: 10.1097/00004647-200207000-00014.


Infusions of [2,4-13C2]-beta-hydroxybutyrate and 1H-13C polarization transfer spectroscopy were used in normal human subjects to detect the entry and metabolism of beta-hydroxybutyrate in the brain. During the 2-hour infusion study, 13C label was detectable in the beta-hydroxybutyrate resonance positions and in the amino acid pools of glutamate, glutamine, and aspartate. With a plasma concentration of 2.25 +/- 0.24 mmol/L (four volunteers), the apparent tissue beta-hydroxybutyrate concentration reached 0.18 +/- 0.06 mmol/L during the last 20 minutes of the study. The relative fractional enrichment of 13C-4-glutamate labeling was 6.78 +/- 1.71%, whereas 13C-4-glutamine was 5.68 +/- 1.84%. Steady-state modeling of the 13C label distribution in glutamate and glutamine suggests that, under these conditions, the consumption of the beta-hydroxybutyrate is predominantly neuronal, used at a rate of 0.032 +/- 0.009 mmol. kg-1. min-1, and accounts for 6.4 +/- 1.6% of total acetyl coenzyme A oxidation. These results are consistent with minimal accumulation of cerebral ketones with rapid utilization, implying blood-brain barrier control of ketone oxidation in the nonfasted adult human brain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Hydroxybutyric Acid / administration & dosage
  • 3-Hydroxybutyric Acid / metabolism*
  • Acetyl Coenzyme A / metabolism
  • Aspartic Acid / metabolism
  • Blood-Brain Barrier
  • Brain / metabolism*
  • Carbon Isotopes
  • Glutamic Acid / metabolism
  • Glutamine / metabolism
  • Humans
  • Ketones / metabolism
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Neurons / metabolism
  • Oxidation-Reduction


  • Carbon Isotopes
  • Ketones
  • Glutamine
  • Aspartic Acid
  • Glutamic Acid
  • Acetyl Coenzyme A
  • 3-Hydroxybutyric Acid