ArticleThe Journal of clinical investigation2011
A ketogenic diet suppresses seizures in mice through adenosine A₁ receptors.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers.
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Who cites it
181 citing papers in PubMed, 300 citations in OpenAlex.
- A Randomized, Placebo-Controlled Crossover Study with Dipyridamole for Restless Legs Syndrome.Movement disorders : official journal of the Movement Disorder Society · 2021Trial
- Energy metabolism, adenosine, and glutamate signaling reprogramming by decanoic acid in Glut1 disorder syndrome.Epilepsia open · 2026Article
- Review
- Therapeutic Potential Target of Adenosine for Epilepsy: Focusing on Its Interaction with the Molecular Epileptogenic Network.Biomolecules · 2026Review
- A study on the mechanism of Buyang Huanwu Decoction in treating epilepsy by regulating adenosine levels.Scientific reports · 2026Article
- Hydroxycarboxylic Acid Receptor 2 Mediates β-hydroxybutyrate's Antiseizure Effect in Mice.Annals of neurology · 2026Article
- Article
- Role of the ketogenic diet in neurodevelopmental disorders: neuroprotection and clinical practice.Frontiers in nutrition · 2026Review
- The interplay between metabolism and neuroinflammation in epilepsy: mechanisms and therapeutic perspectives.Journal of neuroinflammation · 2025Review
- Acute and Intermittent Exogenous Ketosis to Support Recovery From Exercise and Adaptations to Exercise Training: A Narrative Review.Scandinavian journal of medicine & science in sports · 2025Review
- Ketogenic diet in neonates: effects, pitfalls, and a paradigm from a preterm newborn affected by pyruvate dehydrogenase deficiency.Journal of perinatology : official journal of the California Perinatal Association · 2025Review
- Adenosine Kinase: An Epigenetic Modulator and Drug Target.Journal of inherited metabolic disease · 2025Review
- A ketogenic diet decreases sevoflurane-induced burst suppression in rats.Brain research bulletin · 2025Article
- Deep Brain Stimulation Inhibits Epileptic Seizures via Increase of Adenosine Release and Inhibition of ENT1, CD39, and CD73 Expression.Molecular neurobiology · 2025Article
- Impact of the Ketogenic Diet on Neurological Diseases: A Review.Life (Basel, Switzerland) · 2025Review
- Ketogenic diet, adenosine, and dopamine in addiction and psychiatry.Frontiers in nutrition · 2025Review
- Neuroglia and brain energy metabolism.Handbook of clinical neurology · 2025Review
- Acetoacetate, a ketone body, attenuates neuronal bursts in acutely-induced epileptiform slices of the mouse hippocampus.Frontiers in cellular neuroscience · 2025Article
- The hydroxycarboxylic acid receptor HCA2 is required for the protective effect of ketogenic diet in epilepsy.Pharmacology research & perspectives · 2024Article
- Diet and Nutrients in Rare Neurological Disorders: Biological, Biochemical, and Pathophysiological Evidence.Nutrients · 2024Review
121 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
A ketogenic diet (KD) is a high-fat, low-carbohydrate metabolic regimen; its effectiveness in the treatment of refractory epilepsy suggests that the mechanisms underlying its anticonvulsive effects differ from those targeted by conventional antiepileptic drugs. Recently, KD and analogous metabolic strategies have shown therapeutic promise in other neurologic disorders, such as reducing brain injury, pain, and inflammation. Here, we have shown that KD can reduce seizures in mice by increasing activation of adenosine A1 receptors (A1Rs). When transgenic mice with spontaneous seizures caused by deficiency in adenosine metabolism or signaling were fed KD, seizures were nearly abolished if mice had intact A1Rs, were reduced if mice expressed reduced A1Rs, and were unaltered if mice lacked A1Rs. Seizures were restored by injecting either glucose (metabolic reversal) or an A1R antagonist (pharmacologic reversal). Western blot analysis demonstrated that the KD reduced adenosine kinase, the major adenosine-metabolizing enzyme. Importantly, hippocampal tissue resected from patients with medically intractable epilepsy demonstrated increased adenosine kinase. We therefore conclude that adenosine deficiency may be relevant to human epilepsy and that KD can reduce seizures by increasing A1R-mediated inhibition.
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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.