The
triglyceride of heptanoate (C7
fatty acid),
triheptanoin, is a tasteless oil used to treat rare metabolic disorders in USA and France. Heptanoate is metabolized by β-oxidation to provide
propionyl-CoA, which after carboxylation can produce
succinyl-CoA, resulting in anaplerosis - the refilling of the tricarboxylic acid cycle. Heptanoate is also metabolized by the liver to the C5
ketones, β-ketopentanoate and/or β-hydroxypentanoate, which are released into the blood and thought to enter the brain via monocarboxylate transporters. Oral
triheptanoin has recently been discovered to be reproducibly
anticonvulsant in acute and chronic mouse
seizures models. However, current knowledge on alterations of brain metabolism after
triheptanoin administration and anaplerosis via
propionyl-CoA carboxylation in the brain is limited. This review outlines
triheptanoin's unique
anticonvulsant profile and its clinical potential for the treatment of medically
refractory epilepsy. Anaplerosis as a therapeutic approach for the treatment of
epilepsy is discussed. More research is needed to elucidate the
anticonvulsant mechanism of
triheptanoin and to reveal its clinical potential for the treatment of
epilepsy and other disorders of the brain.