Adenosine and Ketogenic Treatments.
Level 5 - mechanism / opinion, no new human data
Narrative review of preclinical animal and in vitro mechanistic studies
PubMed 32954218 · doi:10.1089/caff.2020.0011
What was done
This narrative review evaluated accumulated preclinical and mechanistic evidence examining how adenosine contributes to the anticonvulsant and antiepileptogenic actions of ketogenic treatments (the ketogenic diet, exogenous ketone bodies, and medium-chain triglycerides or fatty acids), focusing on rodent seizure models and in vitro brain slice preparations.
What was found
The abstract reports qualitative findings without quantitative metrics. In multiple rodent models, the antiseizure effects of ketogenic treatments were reversed by adenosine A1 receptor antagonists. Ketogenic diet treatment elevated brain tissue and extracellular adenosine levels. In brain slice preparations, ketogenic conditions reduced neuronal excitability through pre- and postsynaptic A1 receptor-mediated actions. The review also notes potential adenosine-based epigenetic mechanisms and identifies mildly reduced brain glucose as a key trigger for these effects.
Why it matters
Synthesizes the biological mechanisms showing that adenosine A1 receptor signaling is a central mediator of the ketogenic diet's anticonvulsant properties, pointing toward potential pharmacological or metabolic strategies to augment or mimic dietary therapy for refractory epilepsy.
Limits
The abstract reports no quantitative data or effect sizes. The reviewed evidence derives primarily from rodent models and in vitro tissue slices rather than human clinical trials. Antiepileptogenic and neuroprotective endpoints remain under-researched, and human clinical efficacy or safety of targeting these specific pathways is unaddressed.
Cited by
- supports Ketone bodies function as signaling molecules that elevate adenosine and activate the GPR109A receptor.
- supports Fasting and ketogenic diets increase adenosine levels in the brain, and fasting can acutely increase cerebral blood flow by 30%.