Acetoacetate, acetone, and dibenzylamine (a contaminant in l-(+)-beta-hydroxybutyrate) exhibit direct anticonvulsant actions in vivo.

ABSTRACT

PURPOSE: To investigate whether ketone bodies are directly anticonvulsant. METHODS: We tested the effects of acetoacetate (ACA), acetone, and both stereoisomers, D-(-)- and L-(+), of beta-hydroxybutyrate (BHB) on sensory-evoked seizures in Frings audiogenic seizure-susceptible mice. RESULTS: We found that these ketone bodies, with the exception of the D-(-)-isomer of BHB, were anticonvulsant in this model. Furthermore, with gas chromatography-mass spectrometry, we confirmed that the activity of L-(+)-BHB was due to dibenzylamine, a chemical contaminant. CONCLUSIONS: Our data indicate that the anticonvulsant efficacy of the ketogenic diet may be due in part to the direct actions of ACA and acetone.