• P Maciejak, J Szyndler, D Turzyńska, A Sobolewska, K Kołosowska, P Krząścik, and A Płaźnik.
• Department of Neurochemistry, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957 Warsaw, Poland; Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology CePT, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland. Electronic address: piomac@yahoo.com.
• Neuroscience. 2016 Jan 28; 313: 130-48.

AbstractThe effects of a ketogenic diet in controlling seizure activity have been proven in many studies, although its mechanism of action remains elusive in many regards. We hypothesize that the ketogenic diet may exert its antiepileptic effects by influencing tryptophan (TRP) metabolism. The aim of this study was to investigate the influence of octanoic and decanoic fatty acids (FAs), the main components in the MCT diet (medium-chain triglyceride diet, a subtype of the ketogenic diet), on the metabolism of TRP, the activity of the kynurenic pathway and the concentrations of monoamines and amino acids, including branched-chain amino acids (BCAA) and aromatic amino acids (AAA) in rats. The acute effects of FA on the sedation index and hippocampal electrical after-discharge threshold were also assessed. We observed that intragastric administration of FA increased the brain levels of TRP and the central and peripheral concentrations of kynurenic acid (KYNA), as well as caused significant changes in the brain and plasma concentrations of BCAA and AAA. We found that the administration of FA clearly increased the seizure threshold and induced sedation. Furthermore, we have demonstrated that blocking TRP passage into the brain abolished these effects of FA but had no similar effect on the formation of ketone bodies. Given that FAs are major components of a ketogenic diet, it is suggested that the anticonvulsant effects of a ketogenic diet may be at least partly dependent on changes in TRP metabolism. We also propose a more general hypothesis concerning the intracellular mechanism of the ketogenic diet. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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