Ketogenic Diet May Reduce Epileptic Seizures by Changing Brain Signals: Study

A ketogenic diet-rich in fat and extremely low in carbohydrates-has been used for decades to help control seizures in people with epilepsy, especially children whose condition does not respond to medication. Yet the precise biological mechanisms behind its benefits have remained unclear. Now, researchers at Washington University School of Medicine in St. Louis have identified specific changes in brain cells that may explain how the diet suppresses seizures. Their findings were published in Cell Reports.

In many patients, as much as 90% of daily calories must come from fat for the diet to be effective, and even minor lapses can reduce its seizure-controlling benefits. The diet forces the body to switch from using glucose as its primary energy source to producing ketones in the liver. These ketones then serve as fuel for neurons in the brain.

To understand how this metabolic shift affects brain function, the researchers studied mice fed a strict ketogenic diet and analyzed changes in the hippocampus, a region commonly involved in seizure activity. They discovered hundreds of alterations in gene expression, many linked to synapses—the communication points between neurons.

Further experiments showed that excitatory signals, which stimulate neighboring brain cells, were significantly reduced, while inhibitory signals that calm neural activity were increased. This rebalancing dampened overall communication within neural circuits, creating a quieter brain environment less susceptible to seizure-triggering hyperactivity.

These findings suggest that replicating the diet’s molecular and cellular effects through targeted therapies could provide new, less restrictive treatment options for epilepsy patients.

REFERENCE: Stunault, Marion I. et al.; Ketogenic diet dampens excitatory neurotransmission by shrinking synaptic vesicle pools; Cell Reports, Volume 45, Issue 2, 116945; DOI: 10.1016/j.celrep.2026.116945