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
Open accessAbstract
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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“Our findings showed that KD or MAD resulted in better seizure control in children and adolescents with medication-refractory epilepsy (approximately a third of cases) for up to 16 months [10, 11, 16].”
From Effects of ketogenic diet on health outcomes: an umbrella review of meta-analyses of randomized clinical trials (2023) · cites this paper as [11]
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The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet
Olson, C. A., Vuong, H. E., Yano, J. M., Liang, Q. Y., Nusbaum, D. J., & Hsiao, E. Y. (2018) · Cell · doi:10.1016/j.cell.2018.04.027 · Cited by 1,057
Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets
Paoli, A., Rubini, A., Volek, J. S., & Grimaldi, K. A. (2013) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2013.116 · Cited by 885
The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies
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Ketogenic diets for drug-resistant epilepsy
Martin-McGill, K. J., Bresnahan, R., Levy, R. G., & Cooper, P. N. (2020) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001903.pub5 · Cited by 452
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.
- Venue
- Epilepsia
- Publisher
- Wiley
- Published
- 2007-01
- Volume
- 48
- Issue
- 1
- Pages
- 43-58
- ISSN
- 0013-9580 (ISSN-L)
- 1528-1167
- 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
- bronze
- doi.org
- 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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