Acetoacetate, acetone, and dibenzylamine (a contaminant in L-(+)-β-hydroxybutyrate) exhibit direct anticonvulsant actions in vivo

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.