Regional cerebral effects of ketone body infusion with 3-hydroxybutyrate in humans: Reduced glucose uptake, unchanged oxygen consumption and increased blood flow by positron emission tomography. A randomized, controlled trial

PLoS One. 2018 Feb 28;13(2):e0190556. doi: 10.1371/journal.pone.0190556. eCollection 2018.


Ketone bodies are neuroprotective in neurological disorders such as epilepsy. We randomly studied nine healthy human subjects twice-with and without continuous infusion of 3-hydroxybutyrate-to define potential underlying mechanisms, assessed regionally (parietal, occipital, temporal, cortical grey, and frontal) by PET scan. During 3-hydroxybutyrate infusions concentrations increased to 5.5±0.4 mmol/l and cerebral glucose utilisation decreased 14%, oxygen consumption remained unchanged, and cerebral blood flow increased 30%. We conclude that acute 3-hydroxybutyrate infusion reduces cerebral glucose uptake and increases cerebral blood flow in all measured brain regions, without detectable effects on cerebral oxygen uptake though oxygen extraction decreased. Increased oxygen supply concomitant with unchanged oxygen utilisation may contribute to the neuroprotective effects of ketone bodies.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxybutyric Acid / administration & dosage*
  • 3-Hydroxybutyric Acid / blood
  • Aged
  • Biological Transport, Active / drug effects
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / metabolism
  • Cerebrovascular Circulation / drug effects*
  • Cross-Over Studies
  • Female
  • Glucose / metabolism
  • Healthy Volunteers
  • Humans
  • Infusions, Intravenous
  • Ketone Bodies / administration & dosage*
  • Ketone Bodies / blood
  • Male
  • Middle Aged
  • Neuroprotective Agents / administration & dosage
  • Oxygen Consumption / drug effects
  • Positron-Emission Tomography


  • Ketone Bodies
  • Neuroprotective Agents
  • Glucose
  • 3-Hydroxybutyric Acid

Grants and funding

This work was funded by the Danish Council for Strategic Research (grant no.0603-00479B), Aase Danielsen Fund(10-001731), Ferd. Og Ellen Hindsgauls Fund (, and the Danish Medical Association(Jnr.2016-1840/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.