Will Triheptanoin Work?


The conventional mainstream approach to the treatment of epilepsy is to prescribe appropriate antiepileptic drugs. The vast majority of people with epilepsy use and rely upon AEDs to stop or at least reduce recurrent seizures to improve quality of life and reduce morbidity and mortality.

Unfortunately, a significant number of people with epilepsy do not adequately respond to AEDs, and thus require other therapies such as resective surgery, seizure devices, and the ketogenic diet. Surgery remains the current clinical standard in cases of medically refractory epilepsy in which a clear seizure focus can be identified and safely removed, offering a chance for cure. The only device currently available for people with epilepsy in the United States is the vagus nerve stimulator, which is typically relegated for use in those who are not eligible or desirous of resective epilepsy surgery. Other devices for epilepsy that respond to or predict the tell-tale signs of a seizure are in various stages of development and evaluation. The ketogenic diet has been conventionally used to treat children, but also has been effectively employed in the adult epilepsy population. The use of the ketogenic diet was discovered essentially by serendipity decades ago, and over the years has been refined through clinical trials to maximize effectiveness.

Some people with epilepsy find that none of these conventional therapies is effective, which leads us to the very interesting article by Ms. Willis and her associates about using a diet rich in triheptanoin to reduce seizures in mice. The idea behind the experiment is that in seizures, dysfunctional metabolic processes in the brain deplete levels of citric acid cycle intermediates that help to create ATP in aerobic metabolism. This leads to increased neuronal hyperexcitability and reduced levels of the neurotransmitters glutamate, GABA and aspartate, which are ultimately derived from these citric acid cycle intermediates. While the diet used in these experiments was found to have antiseizure properties, the exact mechanism of action remains elusive.

The nature of this discovery is not dissimilar to the way many compounds ultimately are discovered to have antiseizure properties. Many of these compounds are found through drug discovery programs in which the antiseizure property was noticed before the true mechanism of action was ultimately determined. The unique approach here is that the findings were realized beginning with a well-thought-out series of experiments using dietary manipulation. On the other hand, the diet used here may be analogous to the ketogenic diet, requiring years of refinement to optimize effectiveness and patient selection. It remains to be determined if a diet rich in triheptanoin translates into effective or even palatable therapy for people with epilepsy. The final story on this discovery may take years to write, but it is gratifying to those of us in the epilepsy community that researchers like Ms. Willis and her coauthors continue to work on the elusive cure for epilepsy.

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