Annals of Neurology: The Ketogenic Diet Can Provide Protection Against Epileptic Seizures

A new study by U.S. scientists sheds light on how the ketogenic diet may protect against epileptic seizures and the mechanisms underlying this effect.

The study results were published in the journal Annals of Neurology.

A diet very low in carbohydrates and high in fats—the ketogenic diet—has long been used to reduce seizure frequency in people with epilepsy when medications fail, but for a long time scientists did not fully understand why it works.

Now, a research team from the University of Virginia School of Medicine has identified a key biochemical pathway that may explain this effect and pave the way for new treatment approaches.

When the body enters ketosis—a state in which it burns fat instead of carbohydrates—the level of so-called ketone bodies rises in the blood. One of them, β-hydroxybutyrate, actively interacts with a specific receptor in the brain (HCAR2). The researchers found that this interaction calms overly excitable nerve cells, reducing the likelihood of seizure activity.

Hyperexcitable neurons are often the trigger for epileptic seizures, and this mechanism helps explain why the ketogenic diet can be effective where medications fall short.

The researchers also discovered that this receptor is present in the hippocampus—a brain region where seizures often originate—as well as on microglial cells involved in the brain’s immune defense.

Accordingly, ketone bodies may not only reduce neuronal excitability but also influence the brain’s immune environment.

Understanding this mechanism is important not only for epilepsy. According to the authors, it could help in developing drugs that provide the benefits of the ketogenic diet without requiring patients to strictly adhere to a demanding, high-fat, low-carbohydrate regimen, which many find difficult due to side effects and challenges with long-term compliance. It has already been noted that some approved drugs, including niacin (vitamin B3), act on the same receptor as ketone bodies, although it is not yet clear how effective this is in humans.

The scientists plan to further study how this receptor affects immune cells in the brain and how this knowledge can be used to treat not only epilepsy but also other neurological diseases, such as Alzheimer’s disease or multiple sclerosis.