Do ketone bodies mediate the anti-seizure effects of the ketogenic diet?

Neuropharmacology. 2018 May 1;133:233-241. doi: 10.1016/j.neuropharm.2018.01.011. Epub 2018 Jan 8.


Although the mechanisms underlying the anti-seizure effects of the high-fat ketogenic diet (KD) remain unclear, a long-standing question has been whether ketone bodies (i.e., β-hydroxybutyrate, acetoacetate and acetone), either alone or in combination, contribute mechanistically. The traditional belief has been that while ketone bodies reflect enhanced fatty acid oxidation and a general shift toward intermediary metabolism, they are not likely to be the key mediators of the KD's clinical effects, as blood levels of β-hydroxybutyrate do not correlate consistently with improved seizure control. Against this unresolved backdrop, new data support ketone bodies as having anti-seizure actions. Specifically, β-hydroxybutyrate has been shown to interact with multiple novel molecular targets such as histone deacetylases, hydroxycarboxylic acid receptors on immune cells, and the NLRP3 inflammasome. Clearly, as a diet-based therapy is expected to render a broad array of biochemical, molecular, and cellular changes, no single mechanism can explain how the KD works. Specific metabolic substrates or enzymes are only a few of many important factors influenced by the KD that can collectively influence brain hyperexcitability and hypersynchrony. This review summarizes recent novel experimental findings supporting the anti-seizure and neuroprotective properties of ketone bodies.

Keywords: Acetoacetate; Beta-hydroxybutyrate; Epilepsy; Ketogenic diet; Ketone bodies; Neuroprotection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticonvulsants / therapeutic use*
  • Diet, Ketogenic / methods*
  • Humans
  • Ketone Bodies / metabolism*
  • Seizures / diet therapy*


  • Anticonvulsants
  • Ketone Bodies