PubTransformer

A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Is the interaction between fatty acids and tryptophan responsible for the efficacy of a ketogenic diet in epilepsy? The new hypothesis of action.

Abstract The 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.
PMID
Related Publications

The influence of the ketogenic diet on the elemental and biochemical compositions of the hippocampal formation.

Neurobiochemical mechanisms of a ketogenic diet in refractory epilepsy.

Branched-chain amino acids alter neurobehavioral function in rats.

The neuropharmacology of the ketogenic diet.

Seizure control by ketogenic diet-associated medium chain fatty acids.

Authors

Mayor MeshTerms

Diet, Ketogenic

Keywords

NAD(+)/NADH ratio

ketogenic diet

kynurenic acid

octanoic and decanoic fatty acids

seizure activity

tryptophan

Journal Title neuroscience
Publication Year Start




PMID- 26601775
OWN - NLM
STAT- MEDLINE
DCOM- 20160930
LR  - 20171116
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 313
DP  - 2016 Jan 28
TI  - Is the interaction between fatty acids and tryptophan responsible for the
      efficacy of a ketogenic diet in epilepsy? The new hypothesis of action.
PG  - 130-48
LID - 10.1016/j.neuroscience.2015.11.029 [doi]
LID - S0306-4522(15)01018-0 [pii]
AB  - The 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.
CI  - Copyright (c) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Maciejak, P
AU  - Maciejak P
AD  - 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: [email protected]
FAU - Szyndler, J
AU  - Szyndler J
AD  - Department of Experimental and Clinical Pharmacology, Centre for Preclinical
      Research and Technology CePT, Medical University of Warsaw, Banacha 1B, 02-097
      Warsaw, Poland.
FAU - Turzynska, D
AU  - Turzynska D
AD  - Department of Neurochemistry, Institute of Psychiatry and Neurology, Sobieskiego 
      9, 02-957 Warsaw, Poland.
FAU - Sobolewska, A
AU  - Sobolewska A
AD  - Department of Neurochemistry, Institute of Psychiatry and Neurology, Sobieskiego 
      9, 02-957 Warsaw, Poland.
FAU - Kolosowska, K
AU  - Kolosowska K
AD  - Department of Experimental and Clinical Pharmacology, Centre for Preclinical
      Research and Technology CePT, Medical University of Warsaw, Banacha 1B, 02-097
      Warsaw, Poland.
FAU - Krzascik, P
AU  - Krzascik P
AD  - Department of Experimental and Clinical Pharmacology, Centre for Preclinical
      Research and Technology CePT, Medical University of Warsaw, Banacha 1B, 02-097
      Warsaw, Poland.
FAU - Plaznik, A
AU  - Plaznik A
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151119
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Fatty Acids)
RN  - 0 (Hypnotics and Sedatives)
RN  - 0 (Ketone Bodies)
RN  - 8DUH1N11BX (Tryptophan)
RN  - H030S2S85J (Kynurenic Acid)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/*metabolism
MH  - *Diet, Ketogenic
MH  - Epilepsy/*diet therapy/*metabolism
MH  - Fatty Acids/administration & dosage/*metabolism
MH  - Hypnotics and Sedatives/administration & dosage
MH  - Implantable Neurostimulators
MH  - Ketone Bodies/metabolism
MH  - Kynurenic Acid/metabolism
MH  - Male
MH  - Models, Neurological
MH  - Rats, Wistar
MH  - Treatment Outcome
MH  - Tryptophan/*metabolism
OTO - NOTNLM
OT  - NAD(+)/NADH ratio
OT  - ketogenic diet
OT  - kynurenic acid
OT  - octanoic and decanoic fatty acids
OT  - seizure activity
OT  - tryptophan
EDAT- 2015/11/26 06:00
MHDA- 2016/10/01 06:00
CRDT- 2015/11/26 06:00
PHST- 2015/09/15 00:00 [received]
PHST- 2015/11/10 00:00 [revised]
PHST- 2015/11/13 00:00 [accepted]
PHST- 2015/11/26 06:00 [entrez]
PHST- 2015/11/26 06:00 [pubmed]
PHST- 2016/10/01 06:00 [medline]
AID - S0306-4522(15)01018-0 [pii]
AID - 10.1016/j.neuroscience.2015.11.029 [doi]
PST - ppublish
SO  - Neuroscience. 2016 Jan 28;313:130-48. doi: 10.1016/j.neuroscience.2015.11.029.
      Epub 2015 Nov 19.