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

NEUROPHARMACOLOGY

卷:133

Review

Simeone, Timothy A.¹  Simeone, Kristina A.¹  Stafstrom, Carl E.^2,3  Rho, Jong M.^4,5 

[1] Creighton Univ, Sch Med, Dept Pharmacol, Omaha, NE 68178 USA

[2] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA

[4] Univ Calgary, Dept Pediat, Dept Clin Neurosci,Cumming Sch Med, Res Inst,Hotchkiss Brain Inst,Alberta Childrens H, Calgary, AB, Canada

[5] Univ Calgary, Dept Physiol & Pharmacol, Alberta Childrens Hosp, Res Inst,Hotchkiss Brain Inst,Cumming Sch Med, Calgary, AB, Canada

关键词: Epilepsy;    Ketogenic diet;    Ketone bodies;    Beta-hydroxybutyrate;    Acetoacetate;    Neuroprotection;   

DOI  :  10.1016/j.neuropharm.2018.01.011

来源: Elsevier

【 摘 要 】

Although the mechanisms underlying the anti-seizure effects of the high-fat ketogenic diet (IM) remain unclear, a long-standing question has been whether ketone bodies (i.e., beta-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 beta-hydroxybutyrate do not correlate consistently with improved seizure control. Against this unresolved backdrop, new data support ketone bodies as having anti-seizure actions. Specifically, beta-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. (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

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