Researchers clarify how ketogenic diets treat epilepsy, guiding future therapy development

(Press-News.org) Published today in The Lancet Neurology, a new review from the University of Colorado Anschutz in collaboration with UT Southwestern Medical Center, offers the latest scientific explanations for why ketogenic diets reduce seizures in people with epilepsy.

The paper brings together insights from both laboratory discoveries and real‑world patient outcomes, showing that ketogenic diets do far more than reduce seizures. The review outlines how these strict high-fat, low carbohydrate diets strengthen the brain’s energy systems, reduce inflammation and protect neurons - providing therapeutic benefits that many current medications are not yet able to achieve.

“For years, clinicians have seen ketogenic diets reduce seizures in patients who don’t respond to medication but the supporting evidence is scattered across small studies. And while scientists have made progress in understanding why the diet works, few new therapies or large clinical trials have emerged from these discoveries,” said the paper’s first author Anna Figueroa, PharmD, a researcher in the CU Anschutz Skaggs School of Pharmacy and Pharmaceutical Sciences.

Figueroa worked with Charuta Joshi, MBBS, and Manisha Patel, PhD, to synthesize research from the past five years examining the clinical efficacy of ketogenic diets and the underlying mechanisms that drive their effects.

They explain that ketogenic diets significantly limit carbohydrates, so the brain no longer relies on glucose as its main fuel. When this shift happens, the body produces ketones, which provide a steadier, more efficient source of energy. That change helps stabilize overactive neurons and supports healthier energy regulation in the brain. Together, these effects can help make seizures less likely to occur.

“By bringing together the latest clinical evidence and basic science research, we aim to provide an integrated understanding on how these diets work, identify gaps in current knowledge and highlight opportunities for diet implementation strategies. We also hope these insights will encourage the development of drugs that mirror the diet’s therapeutic effects,” Figueroa adds.

These insights, the authors say, not only clarify how ketogenic therapies work but also open the door to new therapies that could replicate the diet’s effects without requiring patients to follow strict, long‑term eating plans.

The review also identifies a major gap: most ketogenic diet research focuses on children. However, while some pediatric studies have compared different ketogenic diets and evaluated them against standard epilepsy care, these studies are still relatively limited. In adults, the evidence gap is even wider and studies comparing ketogenic diets to standard care epilepsy treatments are extremely scarce, with only one randomized controlled trial conducted in adults in the past five years. Research in broader adult populations remains limited, underscoring an urgent need for adult-focused studies.

A key factor highlighted in the review is how the body’s ability to break down fat changes over time. Adults can develop liver changes, often influenced by long-term antiseizure medications, that can affect how well they tolerate or respond to ketogenic diets. This may be one reason early initiation, especially in childhood, appears most effective. The authors emphasize the importance of starting the diet early on to get the most benefits.

Although the review focuses on epilepsy, the basic mechanisms it describes suggest that ketogenic diet approaches could extend beyond seizure disorders. Emerging evidence suggests potential benefits for some people with other neurological conditions, indicating that metabolism‑based therapies may have broader therapeutic value.

Together, the findings in this review underscore the need for earlier adoption of the ketogenic diet, additional large-scale randomized controlled trials to assess long term effects, and continued treatment innovations, both in improving how and when the diet is implemented and in developing diet‑mimicking therapies that are easier for patients to sustain.

About the University of Colorado Anschutz
The University of Colorado Anschutz is a world-class academic medical campus leading transformative advances in science, medicine, education and patient care. The campus includes the University of Colorado’s health professional schools, more than 60 centers and institutes, and two nationally ranked independent hospitals - UCHealth University of Colorado Hospital and Children's Hospital Colorado - which see nearly three million adult and pediatric patient visits each year. Innovative, interconnected and highly collaborative, CU Anschutz delivers life-changing treatments, exceptional patient care and top-tier professional training. The campus conducts world-renowned research supported by $890 million in funding, including $762 million in sponsored awards and $128 million in philanthropic gifts for research.

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