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

Mads Svart; Lars C Gormsen; Jakob Hansen; Dora Zeidler; Michael Gejl; Kim Vang; Joel Aanerud; Niels Moeller

doi:10.1371/journal.pone.0190556

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.

Authors

Mads Svart^{1

2}, Lars C Gormsen³, Jakob Hansen⁴, Dora Zeidler⁵, Michael Gejl^{6

7}, Kim Vang³, Joel Aanerud³, Niels Moeller^{1

2}

Affiliations

¹ Department of Internal Medicine and Endocrinology, Aarhus University Hospital, Aarhus, Denmark.
² Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
³ Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark.
⁴ Section for Forensic Chemistry, Department of Forensic Medicine, Aarhus University Hospital, Aarhus, Denmark.
⁵ Centre of Functionally Integrative Neuroscience (CFIN) and MINDLab, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
⁶ Institute of Biomedicine, Aarhus University, Aarhus, Denmark.
⁷ Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.

Abstract

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

Substances

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 (J.nr.102559), 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.