A new review examines how ketogenic diets influence the brain’s metabolism to reduce seizures, while also revealing major gaps in clinical research.
A new review published in The Lancet Neurology looks at one of the biggest questions in epilepsy care: why do ketogenic diets help some people have fewer seizures? Researchers from the University of Colorado Anschutz and UT Southwestern Medical Center say the answer appears to involve much more than a simple change in food intake.
Their review pulls together findings from recent lab research and patient studies, pointing to several effects happening at once. Ketogenic diets may help the brain produce and use energy more effectively, reduce inflammation, and protect neurons. In other words, the diet may be changing the brain’s internal environment in ways that make seizures less likely.
“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.
Bringing Together Recent Research
Figueroa collaborated with Charuta Joshi, MBBS, and Manisha Patel, PhD, to analyze research published over the past five years on the clinical effectiveness of ketogenic diets and the biological processes that may explain their benefits.
Ketogenic diets sharply restrict carbohydrate intake, which causes the brain to shift away from glucose as its main energy source. In response, the body begins producing ketones, molecules that can serve as an alternative fuel.
This metabolic change may provide a steadier energy supply for the brain. It can also help calm overly active neurons and improve how the brain regulates energy. Together, these changes may reduce the likelihood of seizures.
“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.
The authors say these findings clarify how ketogenic therapies influence the brain and could guide the development of new treatments that reproduce the diet’s benefits without requiring patients to maintain strict long-term eating plans.
Age, Metabolism, and Timing of Treatment
The review also highlights a major research gap. Most studies on ketogenic diets for epilepsy focus on children. Although some pediatric research has compared different ketogenic approaches and evaluated them alongside standard epilepsy treatments, the number of studies remains limited.
Evidence in adults is even more scarce. In the past five years, only one randomized controlled trial has compared ketogenic diets with standard epilepsy care in adults. Research involving larger adult populations is still limited, pointing to a clear need for more adult-focused clinical studies.
The review also discusses how the body’s ability to process fat can change over time. Adults may develop liver changes, sometimes linked to long-term antiseizure medication use, that can affect how well they tolerate or respond to ketogenic diets.
This may help explain why starting the diet earlier, particularly during childhood, often appears to produce stronger results. The authors therefore emphasize the potential benefits of introducing ketogenic therapy earlier in treatment.
Although the review centers on epilepsy, the biological mechanisms it describes may apply to other neurological conditions as well. Early research suggests that metabolism-based treatments such as ketogenic diets could benefit some people with other brain disorders.
Overall, the authors say the findings support earlier consideration of ketogenic diets, larger randomized controlled trials to evaluate long-term outcomes, and continued efforts to develop therapies that mimic the diet’s effects while remaining easier for patients to maintain.
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