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

Timothy A. Simeone, Kristina A. Simeone, Carl Stafstrom, Jong M. Rho

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish (US)
Pages (from-to)233-241
Number of pages9
JournalNeuropharmacology
Volume133
DOIs
StatePublished - May 1 2018

Keywords

  • Acetoacetate
  • Beta-hydroxybutyrate
  • Epilepsy
  • Ketogenic diet
  • Ketone bodies
  • Neuroprotection

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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