Researchers Uncover Mechanism Behind Keto Diet’s Seizure Prevention

Researchers at the University of Virginia School of Medicine have unveiled a significant mechanism through which the low-carbohydrate ketogenic diet may prevent seizures in patients who do not respond to traditional medications. This discovery, published in the journal Annals of Neurology, offers new insights into how the diet, which has been utilized for nearly a century, could also have implications for neurodegenerative diseases like Alzheimer’s and Parkinson’s.

The ketogenic diet, often referred to as keto, has been recognized for its ability to reduce seizures since the 1920s. Despite its popularity, healthcare professionals have struggled to fully understand the underlying biological processes at play. The research team, led by Jaideep Kapur, an expert in epilepsy at UVA Health, has made strides in identifying how the diet exerts its effects.

Kapur and his colleagues discovered that the body’s conversion of the ketogenic diet into a ketone body named β-hydroxybutyrate plays a crucial role in regulating brain activity. This process involves a specific receptor known as hydroxycarboxylic acid receptor 2, or HCAR2, which assists in modulating the activity and communication of brain cells, thereby reducing seizure occurrences.

“Many individuals are unable to tolerate the keto diet due to its high-fat content and associated side effects,” Kapur explained. “This discovery opens the door for developing medications that mimic the beneficial effects of the keto diet without the need for such a restrictive eating plan.”

Understanding the Science Behind Keto

The ketogenic diet encourages the body to use fat as its primary fuel source instead of carbohydrates. This metabolic shift can lead to significant weight loss, but it also triggers various physiological changes that are not well-tolerated by everyone. During ketosis, the liver produces ketones, which serve as an alternative energy source for brain cells.

Kapur’s research team, including researcher Soudabeh Naderi, investigated the interaction between β-hydroxybutyrate and neurons, the brain’s nerve cells. They found that this ketone interacts with HCAR2 to calm hyperactive neurons, which are often responsible for triggering seizures. Such excitability is also observed in early stages of neurodegenerative conditions, including Alzheimer’s disease and autism.

The team mapped the presence of HCAR2 in the hippocampus, a brain region where seizures frequently initiate. Their study revealed that this receptor is concentrated in specific cells known to be associated with seizure activity, as well as in immune cells called microglia, which help protect the brain.

Potential for New Therapeutics

The implications of this research extend beyond epilepsy. The findings suggest a pathway for developing drugs that could replicate the neuroprotective benefits of the ketogenic diet without requiring patients to adhere to its stringent dietary restrictions. For instance, preliminary findings indicate that niacin, a vitamin B3 supplement already approved by the FDA for lowering lipids, may act on HCAR2 and provide similar protective effects.

Kapur emphasized the potential for further exploration of HCAR2’s role in modulating brain immune responses through microglia. “Our ongoing studies aim to develop innovative therapies for conditions like drug-resistant epilepsy, multiple sclerosis, and Alzheimer’s disease,” he noted.

The research highlights the promise of understanding dietary impacts on neurological health. As scientists continue to unravel these complexities, there is hope that patients might benefit from effective, non-invasive treatments that harness the power of dietary components while minimizing burdensome lifestyle changes.

For further details, the study can be found under the title “Hydroxycarboxylic Acid Receptor 2 Mediates β‐hydroxybutyrate’s Antiseizure Effect in Mice” in the Annals of Neurology, published in March 2025. This groundbreaking work adds to the growing body of evidence supporting dietary interventions in managing neurological disorders.