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Cited by 523Diet and metabolism studiesEpilepsy research and treatmentDietary Effects on Health

The DOI matches its Crossref record; 156 of the 157 references it cites were found in a registry or an index.

Anticonvulsant Mechanisms of the Ketogenic Diet

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Bough, Kristopher J., Rho, Jong M.·2007·Epilepsia
DOI 10.1111/j.1528-1167.2007.00915.x
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Abstract

Summary: The ketogenic diet (KD) is a broadly effective treatment for medically refractory epilepsy. Despite nearly a century of use, the mechanisms underlying its clinical efficacy remain unknown. In this review, we present one intersecting view of how the KD may exert its anticonvulsant activity against the backdrop of several seemingly disparate mechanistic theories. We summarize key insights gleaned from experimental and clinical studies of the KD, and focus particular attention on the role that ketone bodies, fatty acids, and limited glucose may play in seizure control. Chronic ketosis is anticipated to modify the tricarboxcylic acid cycle to increase GABA synthesis in brain, limit reactive oxygen species (ROS) generation, and boost energy production in brain tissue. Among several direct neuro‐inhibitory actions, polyunsaturated fatty acids increased after KD induce the expression of neuronal uncoupling proteins (UCPs), a collective up‐regulation of numerous energy metabolism genes, and mitochondrial biogenesis. These effects further limit ROS generation and increase energy production. As a result of limited glucose and enhanced oxidative phosphorylation, reduced glycolytic flux is hypothesized to activate metabolic K ATP channels and hyperpolarize neurons and/or glia. Although it is unlikely that a single mechanism, however well substantiated, will explain all of the diet's clinical benefits, these diverse, coordinated changes seem poised to stabilize synaptic function and increase the resistance to seizures throughout the brain.

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Research works printed but not linked: 1

  1. Stafstrom CE, 2005, 2‐deoxyglucose exerts anticonvulsant and antiepileptic actions in experimental epilepsy models, Epilepsia, 46, 268

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Metadata

Authors
Bough, K. J., & Rho, J. M.
Affiliations
  • United States Food and Drug Administration (US)
  • Barrow Neurological Institute (US)
Corresponding author
Bough, Kristopher J.
ORCID
Venue
Epilepsia
Publisher
Wiley
Published
2007-01
Volume
48
Issue
1
Pages
43-58
ISSN
  • 0013-9580 (ISSN-L)
  • 1528-1167
DOI
10.1111/j.1528-1167.2007.00915.x
OpenAlex
W2068432022
Cited by
523
References
157
Citations by year
2026: 22 · 2025: 16 · 2024: 27 · 2023: 24 · 2022: 36 · 2021: 32 · 2020: 38 · 2019: 30 · 2018: 22 · 2017: 23 · 2016: 26 · 2015: 20 · 2014: 30 · 2013: 24 · 2012: 24
FWCI
3.27
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 3 d)
Locations
  • Epilepsia (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
  • Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
  • Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
Keywords
ketogenic diet, anticonvulsant mechanism, drug-resistant epilepsy, ketone bodies, fatty acids, glucose restriction, TCA cycle, GABA synthesis, reactive oxygen species, mitochondrial biogenesis, uncoupling proteins, polyunsaturated fatty acids, glycolytic flux, ATP-sensitive potassium channels, neuronal hyperpolarization, brain energy metabolism, oxidative phosphorylation
MeSH terms
Dietary Carbohydrates, Dietary Fats, Dietary Proteins, Energy Metabolism, Epilepsy, Humans, Ketone Bodies, Ketosis, Treatment Outcome, Reactive Oxygen Species, Diet, Carbohydrate-Restricted

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