Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats.
Level 5 - mechanism / opinion, no new human data
Bench and animal research without human clinical data.
PubMed 23552496 · doi:10.1152/ajpregu.00506.2012
What was done
Adult male rats (n = 60) with implanted radiotelemetry units for electroencephalogram (EEG) monitoring received a single oral dose of R,S-1,3-butanediol acetoacetate diester (BD-AcAc2), 1,3-butanediol (BD), or water 30 minutes prior to 5 atmospheres absolute (ATA) oxygen exposure in a hyperbaric chamber. Latency to seizure was recorded up to the onset of increased EEG activity and tonic-clonic contractions. Blood chemistry, blood gases, β-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone were measured in an additional 18 catheterized rats at room pressure.
What was found
BD-AcAc2 rapidly (30 min) and persistently (>4 h) elevated BHB (>3 mM) and AcAc (>3 mM). Oral BD-AcAc2 increased latency to seizure by 574 ± 116% compared with water control. BD alone induced ketosis with elevated BHB (>5 mM) without raising AcAc or acetone and failed to increase seizure latency, indicating seizure protection was mediated by AcAc and acetone rather than BHB.
Why it matters
Exogenous ketone ester administration rapidly induces high-grade therapeutic ketosis without dietary restriction and provides substantial protection against hyperbaric oxygen-induced CNS toxicity in rats.
Limits
This is a preclinical animal model using only adult male rats exposed to extreme hyperbaric oxygen (5 ATA); translational relevance to humans and other seizure etiologies is unknown. Only a single acute dose was tested.
Cited by
- supports In an animal model of tonic-clonic seizures induced by hyperbaric oxygen, 1,3-butanediol acetoacetate diester increased the latency to seizure by 600%.
- supports 1,3-butanediol acetoacetate diester elevates blood levels of beta-hydroxybutyrate and acetoacetate in approximately a one-to-one ratio.