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Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders.

Abstract High-fat, low-carbohydrate diets, known as ketogenic diets, have been used as a non-pharmacological treatment for refractory epilepsy. A key mechanism of this treatment is thought to be the generation of ketones, which provide brain cells (neurons and astrocytes) with an energy source that is more efficient than glucose, resulting in beneficial downstream metabolic changes, such as increasing adenosine levels, which might have effects on seizure control. However, some studies have challenged the central role of ketones because medium-chain fatty acids, which are part of a commonly used variation of the diet (the medium-chain triglyceride ketogenic diet), have been shown to directly inhibit AMPA receptors (glutamate receptors), and to change cell energetics through mitochondrial biogenesis. Through these mechanisms, medium-chain fatty acids rather than ketones are likely to block seizure onset and raise seizure threshold. The mechanisms underlying the ketogenic diet might also have roles in other disorders, such as preventing neurodegeneration in Alzheimer's disease, the proliferation and spread of cancer, and insulin resistance in type 2 diabetes. Analysing medium-chain fatty acids in future ketogenic diet studies will provide further insights into their importance in modified forms of the diet. Moreover, the results of these studies could facilitate the development of new pharmacological and dietary therapies for epilepsy and other disorders.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title the lancet. neurology
Publication Year Start


 


PMID- 29263011
OWN - NLM
STAT- MEDLINE
DCOM- 20171227
LR  - 20171227
IS  - 1474-4465 (Electronic)
IS  - 1474-4422 (Linking)
VI  - 17
IP  - 1
DP  - 2018 Jan
TI  - Mechanisms of action for the medium-chain triglyceride ketogenic diet in
      neurological and metabolic disorders.
PG  - 84-93
LID - S1474-4422(17)30408-8 [pii]
LID - 10.1016/S1474-4422(17)30408-8 [doi]
AB  - High-fat, low-carbohydrate diets, known as ketogenic diets, have been used as a
      non-pharmacological treatment for refractory epilepsy. A key mechanism of this
      treatment is thought to be the generation of ketones, which provide brain cells
      (neurons and astrocytes) with an energy source that is more efficient than
      glucose, resulting in beneficial downstream metabolic changes, such as increasing
      adenosine levels, which might have effects on seizure control. However, some
      studies have challenged the central role of ketones because medium-chain fatty
      acids, which are part of a commonly used variation of the diet (the medium-chain 
      triglyceride ketogenic diet), have been shown to directly inhibit AMPA receptors 
      (glutamate receptors), and to change cell energetics through mitochondrial
      biogenesis. Through these mechanisms, medium-chain fatty acids rather than
      ketones are likely to block seizure onset and raise seizure threshold. The
      mechanisms underlying the ketogenic diet might also have roles in other
      disorders, such as preventing neurodegeneration in Alzheimer's disease, the
      proliferation and spread of cancer, and insulin resistance in type 2 diabetes.
      Analysing medium-chain fatty acids in future ketogenic diet studies will provide 
      further insights into their importance in modified forms of the diet. Moreover,
      the results of these studies could facilitate the development of new
      pharmacological and dietary therapies for epilepsy and other disorders.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Augustin, Katrin
AU  - Augustin K
AD  - Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway
      University of London, Egham, UK.
FAU - Khabbush, Aziza
AU  - Khabbush A
AD  - UCL Great Ormond Street Institute of Child Health, University College London,
      London, UK.
FAU - Williams, Sophie
AU  - Williams S
AD  - Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology,
      University College London, London, UK.
FAU - Eaton, Simon
AU  - Eaton S
AD  - UCL Great Ormond Street Institute of Child Health, University College London,
      London, UK.
FAU - Orford, Michael
AU  - Orford M
AD  - UCL Great Ormond Street Institute of Child Health, University College London,
      London, UK.
FAU - Cross, J Helen
AU  - Cross JH
AD  - Neurosciences Unit, UCL Institute of Child Health, University College London,
      London, UK.
FAU - Heales, Simon J R
AU  - Heales SJR
AD  - UCL Great Ormond Street Institute of Child Health, University College London,
      London, UK.
FAU - Walker, Matthew C
AU  - Walker MC
AD  - Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology,
      University College London, London, UK.
FAU - Williams, Robin S B
AU  - Williams RSB
AD  - Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway
      University of London, Egham, UK. Electronic address: [email protected]
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20171216
PL  - England
TA  - Lancet Neurol
JT  - The Lancet. Neurology
JID - 101139309
RN  - 0 (Caprylates)
RN  - 0 (Decanoic Acids)
RN  - 4G9EDB6V73 (decanoic acid)
RN  - OBL58JN025 (octanoic acid)
SB  - IM
MH  - Alzheimer Disease/*drug therapy
MH  - Caprylates/*metabolism
MH  - Decanoic Acids/*metabolism
MH  - Diabetes Mellitus/*diet therapy
MH  - Diet, Ketogenic/*methods
MH  - Humans
MH  - Neoplasms/*diet therapy
MH  - Seizures/*diet therapy
EDAT- 2017/12/22 06:00
MHDA- 2017/12/22 06:00
CRDT- 2017/12/22 06:00
PHST- 2017/06/11 00:00 [received]
PHST- 2017/11/03 00:00 [revised]
PHST- 2017/11/20 00:00 [accepted]
PHST- 2017/12/22 06:00 [entrez]
PHST- 2017/12/22 06:00 [pubmed]
PHST- 2017/12/22 06:00 [medline]
AID - S1474-4422(17)30408-8 [pii]
AID - 10.1016/S1474-4422(17)30408-8 [doi]
PST - ppublish
SO  - Lancet Neurol. 2018 Jan;17(1):84-93. doi: 10.1016/S1474-4422(17)30408-8. Epub
      2017 Dec 16.