Metabolic challenges: Ketogenic diet in brain injury

Mauro Oddo (Lausanne, Switzerland)

Alternative substrates: Acetoacetate, beta-Hydroxybutyrate (BHB) = ketone bodies from adipolysis in liver

  • Mono-carboxylate transporter (MCT) directly transfers ketones into mitochondria
  • bypass glycolysis –> Acetyl CoA –> energy production
  • can be utilised by brain, muscle, heart, kidney but not liver

Must distinguish physiological ketone production + nutritional intervention from pathophysiological production (DKA)

 

Ketones in Brain Injury

  • protect brain from glycolytic flux
  • confer energetic advantage
  • decrease oxidative stress and inflammation

In humans with acute TBI

  • brain ketone levels (extracellular fluid) correlate well with blood ketone levels
  • intense production of ketones in acute phase, up to 1mmol/L (even higher on ketogenic diet)

Ketogenic diets

Medium-chain triglycerides – slow, relatively limited increase in plasma levels over time (~0.5mmol/L BHB)

Ketone esters – rapid increase to keto-therapeutic plasma levels (2-3mmol/L BHB) in healthy volunteers

Brain energy provision by ketones increases proportionately with increasing plasma ketone levels (0.5mM => 5% energy provision; 1.5mM => 20%; 5mM => 60%)

*Upcoming trial, awaiting ethical approval