Triheptanoin as a nutraceutical and its potential use in epilepsy

The odd-chain triglyceride triheptanoin is metabolized into heptanoate and C5 ketones, which provide highly effective anaplerosis, i.e., refilling of the tricyclic acid cycle with intermediates. Triheptanoin is more efficient than traditional, fat-rich, C4-ketogenic diet in providing anaplerosis, and has been successfully applied to treat long-chain fatty acid oxidation disorders. A metabolic imbalance is also observed in epileptic neurons and is thought to originate from ATP depletion, in addition to being involved in exacerbating seizures. An anaplerotic diet can counteract this effect, by sustaining mitochondrial respiration and, possibly, glycolysis. Indeed, studies on pharmacological and genetic animal models of epilepsy have shown that triheptanoin can reduce both electrographic and behavioral seizures. On the other hand, results on patients can vary according to the specific pathological condition. Interestingly, triheptanoin can exert neuroprotective effects in experimental models of brain ischemia and neurodegeneration. A complete understanding of its mechanisms of action on cellular metabolism and on neuronal function, in addition to a standardization of administration protocols, will be instrumental in fully supporting the efficacy of triheptanoin in epilepsy and in other brain diseases.