A ketogenic diet suppresses seizures in mice through adenosine A₁ receptors.
Level 5 - mechanism / opinion, no new human data
Bench, animal, and ex vivo tissue research without a clinical trial
PubMed 21701065 · doi:10.1172/JCI57813
What was done
Investigated the anticonvulsant mechanism of a ketogenic diet using transgenic mice with spontaneous seizures caused by deficient adenosine metabolism or signaling. Mice with intact, reduced, or absent adenosine A1 receptors were fed a ketogenic diet, with seizure reversal tested using glucose or an A1 receptor antagonist. Western blot was used to assess adenosine kinase expression in mouse brain tissue and in resected hippocampal tissue from patients with medically intractable epilepsy.
What was found
The ketogenic diet nearly abolished spontaneous seizures in mice with intact A1 receptors, reduced seizures in mice with reduced A1 receptors, and did not alter seizures in mice lacking A1 receptors. Seizures were restored by administering glucose or an A1 receptor antagonist. The diet decreased adenosine kinase in mice, while resected human epileptic hippocampal tissue showed increased adenosine kinase. No exact numerical data or sample sizes were reported in the abstract.
Why it matters
Identifies adenosine kinase reduction and adenosine A1 receptor activation as a key mechanism underlying the anticonvulsant effect of the ketogenic diet, providing a mechanistic link to human refractory epilepsy.
Limits
Primary therapeutic findings are restricted to transgenic mouse models and have not been confirmed in clinical human trials. The human component is limited to observational ex vivo tissue analysis. No numerical quantities, sample sizes, or variance estimates are provided in the abstract.
Cited by
- supports Fasting and ketogenic diets increase adenosine levels in the brain, and fasting can acutely increase cerebral blood flow by 30%.