Acetoacetate, Acetone, and Dibenzylamine (a Contaminant in l‐(+)‐β‐Hydroxybutyrate) Exhibit Direct Anticonvulsant Actions in Vivo

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Abstract
Summary: 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 β-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.