Boosting the injured brain with supplemental energy fuels

  • Mauro Oddo
  • Paul Vespa
  • David K. Menon
What's New in Intensive Care


Clinical investigation, using cerebral metabolic assessment with positron emission tomography, magnetic resonance spectroscopy, and regional cerebral microdialysis, has repeatedly disclosed major alterations of cerebral energy metabolism in the aftermath of traumatic brain injury (TBI). Impairment of cerebral energy metabolism is characterized by elevated cerebral glucose demand, increased glycolysis, and diversion of the main substrate, glucose, to be used in injury-related reparative pathways, such as the pentose phosphate pathway. Ultimately, these secondary processes lead to a reduction of the cerebral metabolic rate of glucose and a decreased availability of cerebral extracellular glucose. To compensate for glucose shortage, cerebral lactate metabolism and uptake are increased in patients with TBI [1]. Use of alternative cerebral energy substrates—including lactate (LAC), but also ketone bodies (KB) such as β-hydroxybutyrate (BHB) and acetoacetate (AcAc)—may therefore...



Mauro Oddo is supported by research grants from the Swiss National Science Foundation.

Compliance with ethical standards

Conflicts of interest

The authors have no conflict of interest to declare.


  1. 1.
    Glenn TC, Martin NA, Horning MA, McArthur DL, Hovda DA, Vespa P, Brooks GA (2015) Lactate: brain fuel in human traumatic brain injury: a comparison with normal healthy control subjects. J Neurotrauma 32:820–832CrossRefGoogle Scholar
  2. 2.
    Magistretti PJ, Allaman I (2018) Lactate in the brain: from metabolic end-product to signalling molecule. Nat Rev Neurosci 19:235–249CrossRefGoogle Scholar
  3. 3.
    Prins ML, Matsumoto JH (2014) The collective therapeutic potential of cerebral ketone metabolism in traumatic brain injury. J Lipid Res 55:2450–2457CrossRefGoogle Scholar
  4. 4.
    Jalloh I, Helmy A, Howe DJ, Shannon RJ, Grice P, Mason A, Gallagher CN, Murphy MP, Pickard JD, Menon DK et al (2018) A comparison of oxidative lactate metabolism in traumatically injured brain and control brain. J Neurotrauma 35:2025–2035CrossRefGoogle Scholar
  5. 5.
    Wolahan SM, Mao HC, Real C, Vespa PM, Glenn TC (2018) Lactate supplementation in severe traumatic brain injured adults by primed constant infusion of sodium l-lactate. J Neurosci Res 96:688–695CrossRefGoogle Scholar
  6. 6.
    Carteron L, Solari D, Patet C, Quintard H, Miroz JP, Bloch J, Daniel RT, Hirt L, Eckert P, Magistretti PJ et al (2018) Hypertonic lactate to improve cerebral perfusion and glucose availability after acute brain injury. Crit Care Med 46:1649–1655CrossRefGoogle Scholar
  7. 7.
    Ichai C, Payen JF, Orban JC, Quintard H, Roth H, Legrand R, Francony G, Leverve XM (2013) Half-molar sodium lactate infusion to prevent intracranial hypertensive episodes in severe traumatic brain injured patients: a randomized controlled trial. Intensive Care Med 39:1413–1422CrossRefGoogle Scholar
  8. 8.
    Augustin K, Khabbush A, Williams S, Eaton S, Orford M, Cross JH, Heales SJR, Walker MC, Williams RSB (2018) Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders. Lancet Neurol 17:84–93CrossRefGoogle Scholar
  9. 9.
    Stubbs BJ, Cox PJ, Evans RD, Santer P, Miller JJ, Faull OK, Magor-Elliott S, Hiyama S, Stirling M, Clarke K (2017) On the metabolism of exogenous ketones in humans. Front Physiol 8:848CrossRefGoogle Scholar
  10. 10.
    Xin L, Ipek Ö, Beaumont M, Shevlyakova M, Christinat N, Masoodi M, Greenberg N, Gruetter R, Cuenoud B (2018) Nutritional ketosis increases NAD+/NAD+ ratio in healthy human brain: an in vivo study by 31P-MRS. Front Nutr 5:62CrossRefGoogle Scholar
  11. 11.
    Hashim SA, VanItallie TB (2014) Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester. J Lipid Res 55:1818–1826CrossRefGoogle Scholar
  12. 12.
    White H, Venkatesh B (2011) Clinical review: ketones and brain injury. Crit Care 15:219CrossRefGoogle Scholar
  13. 13.
    Bernini A, Masoodi M, Solari D, Miroz JP, Carteron L, Christinat N, Morelli P, Beaumont M, Abed-Maillard S, Hartweg M et al (2018) Modulation of cerebral ketone metabolism following traumatic brain injury in humans. J Cereb Blood Flow Metab 24:271678X18808947.
  14. 14.
    Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW et al (2016) Nutritional ketosis alters fuel preference and thereby endurance performance in athletes. Cell Metab 24:256–268CrossRefGoogle Scholar
  15. 15.
    Svart M, Gormsen LC, Hansen J, Zeidler D, Gejl M, Vang K, Aanerud J, Moeller N (2018) 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 13:e0190556CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Intensive Care Medicine, Critical Care Clinical Research UnitCHUV-Lausanne University HospitalLausanneSwitzerland
  2. 2.Division of Neurosurgery and Department of NeurologyUniversity of California at Los Angeles School of MedicineLos AngelesUSA
  3. 3.USC Stevens Neuroimaging and Informatics Institute, University of Southern CaliforniaLos AngelesUSA
  4. 4.NIHR Global Health Research Group on NeurotraumaUniversity of CambridgeCambridgeUK
  5. 5.Division of Anesthesia, Department of MedicineUniversity of CambridgeCambridgeUK

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