ReviewFrontiers in neuroscience2019
Ketone Administration for Seizure Disorders: History and Rationale for Ketone Esters and Metabolic Alternatives.
Review in Frontiers in neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- The Efficacy of Ketogenic Therapies in the Clinical Management of People with Neurodegenerative Disease: A Systematic Review.Advances in nutrition (Bethesda, Md.) · 2021Pooled it
- The ketogenic diet ameliorates behavioral abnormalities in a PTZ-induced zebrafish larvae model via modulating neurotransmitter balance.IBRO neuroscience reports · 2026Article
- Article
- Review
- Identification and verification of hub genes related to mitochondrial dysfunction in epilepsy based on bioinformatics analysis.BMC neurology · 2026Article
- The science of ketogenic supplements for athletes: boosting endurance, efficiency, and energy metabolism.Nutrition & metabolism · 2025Review
- Efficacy and tolerability of a low-glycemic-index ketogenic diet in Angelman syndrome: findings from the DIANE study.Orphanet journal of rare diseases · 2025Article
- Salutary Effects of Nutritional Ketosis for the Diseased Human Heart.Current atherosclerosis reports · 2025Review
- A primary mechanism for efficacy of the ketogenic diet may be energy repletion at the tripartite synapse.Journal of neural engineering · 2025Article
- Exogenous Ketone Supplementation Enhances the Anti-Epileptic Effect of Levetiracetam in Wistar Albino Glaxo/Rijswijk Rats.Nutrients · 2025Article
- A ketogenic diet decreases sevoflurane-induced burst suppression in rats.Brain research bulletin · 2025Article
- VDAC1 Inhibition Mitigates Inflammatory Status and Oxidative Stress in Epileptic Mice Treated with the Ketogenic Diet.Neurochemical research · 2025Article
- Recent Advances in Bioactive Flavonoids-based Nanotherapeutics as Promising Neuroprotectants in Epilepsy.Current aging science · 2025Review
- A review of nutritional recommendations for scuba divers.Journal of the International Society of Sports Nutrition · 2024Review
- Rapid modulation of interscapular brown adipose tissue mitochondrial activity by ketosis induced by 1,3-butanediol administration to rats.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Brain Metabolism in Health and Neurodegeneration: The Interplay Among Neurons and Astrocytes.Cells · 2024Review
- Putative Role of Adenosine A1 Receptors in Exogenous Ketone Supplements-Evoked Anti-Epileptic Effect.International journal of molecular sciences · 2024Review
- Eu- or hypoglycemic ketosis and ketoacidosis in children: a review.Pediatric nephrology (Berlin, Germany) · 2024Review
- 1,3-Butanediol Administration Increases β-Hydroxybutyrate Plasma Levels and Affects Redox Homeostasis, Endoplasmic Reticulum Stress, and Adipokine Production in Rat Gonadal Adipose Tissue.Antioxidants (Basel, Switzerland) · 2023Article
- (R,R)-BD-AcAc2 Mitigates Chronic Colitis in Rats: A Promising Multi-Pronged Approach Modulating Inflammasome Activity, Autophagy, and Pyroptosis.Pharmaceuticals (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ketogenic diet (KD) is a high-fat, low-carbohydrate treatment for medically intractable epilepsy. One of the hallmark features of the KD is the production of ketone bodies which have long been believed, but not yet proven, to exert direct anti-seizure effects. The prevailing view has been that ketosis is an epiphenomenon during KD treatment, mostly due to clinical observations that blood ketone levels do not correlate well with seizure control. Nevertheless, there is increasing experimental evidence that ketone bodies alone can exert anti-seizure properties through a multiplicity of mechanisms, including but not limited to: (1) activation of inhibitory adenosine and ATP-sensitive potassium channels; (2) enhancement of mitochondrial function and reduction in oxidative stress; (3) attenuation of excitatory neurotransmission; and (4) enhancement of central γ-aminobutyric acid (GABA) synthesis. Other novel actions more recently reported include inhibition of inflammasome assembly and activation of peripheral immune cells, and epigenetic effects by decreasing the activity of histone deacetylases (HDACs). Collectively, the preclinical evidence to date suggests that ketone administration alone might afford anti-seizure benefits for patients with epilepsy. There are, however, pragmatic challenges in administering ketone bodies in humans, but prior concerns may largely be mitigated through the use of ketone esters or balanced ketone electrolyte formulations that can be given orally and induce elevated and sustained hyperketonemia to achieve therapeutic effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.