For more than a century, doctors have used ketogenic diets to help control seizures in people with epilepsy, particularly when medications fail. Now, a new scientific review is helping clarify exactly how these diets work and why they may benefit some patients.
The paper, published in The Lancet Neurology, synthesizes findings from recent clinical studies and laboratory research examining the biological effects of ketogenic diets. Researchers from the University of Colorado Anschutz and UT Southwestern Medical Center reviewed evidence from the past five years to better understand how the diet reduces seizures and influences brain metabolism.
Ketogenic diets are built around a simple but powerful metabolic shift. By sharply restricting carbohydrates and emphasizing fat, the diet pushes the body to produce molecules called ketones. Instead of relying primarily on glucose from carbohydrates, the brain begins using ketones as an alternative fuel.
Researchers say that metabolic change appears to stabilize brain activity in several ways.
When the brain runs on ketones, energy production becomes more efficient and neurons may become less prone to sudden bursts of electrical activity that trigger seizures. The review also points to evidence that ketogenic diets may reduce inflammation and help protect nerve cells from damage.
Together, these effects may explain why ketogenic diets can reduce seizure frequency in people whose epilepsy does not respond to medication.
“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,” said Anna Figueroa, PharmD, a researcher in the CU Anschutz Skaggs School of Pharmacy and Pharmaceutical Sciences and the paper’s first author.
“And while scientists have made progress in understanding why the diet works, few new therapies or large clinical trials have emerged from these discoveries.”
The review highlights that ketogenic diets appear to influence several biological pathways at once, including brain energy metabolism, oxidative stress and signaling between neurons. These overlapping effects may explain why the diet can succeed where some drugs fail.
The findings also point to a growing interest among scientists in developing medications that mimic the metabolic effects of ketogenic diets without requiring patients to follow such strict eating plans.
Researchers say the diet’s benefits are best documented in children with drug-resistant epilepsy, where it has been used clinically for decades. Evidence in adults remains much more limited.
The review notes that only one randomized controlled trial comparing ketogenic diets with standard epilepsy care in adults has been published in the past five years. More large clinical studies are needed to understand how well the approach works across different age groups and types of epilepsy.
The authors also point out that long-term use of certain antiseizure medications can affect how the body processes fats. These changes may influence how well adults tolerate ketogenic diets and could partly explain why earlier treatment appears to be more effective in some patients.
Although the focus of the review is epilepsy, the biological mechanisms behind ketogenic diets have attracted interest in other neurological conditions as well. Researchers say metabolism-based therapies may eventually play a role in treating a wider range of brain disorders.
For now, however, ketogenic diets remain a specialized medical therapy that typically requires supervision from clinicians and dietitians.
By bringing together new laboratory discoveries and clinical evidence, the researchers hope their analysis will help guide future studies and lead to new treatments inspired by the diet’s metabolic effects.
The press release did not specify external funding for the review article.