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Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor of Molecular Cell Biology Robin S. Williams, Royal Holloway University of London, UK
- Second opponent: Clinical Associate Professor Maria J. Miranda, University of Copenhagen, Denmark,
- Third member and chair of the evaluation committee: Professor II Anders Christofer Lundqvist, University of Oslo
Chair of the Defence
Professor Emeritus Leif Gjerstad, University of Oslo
Principal Supervisor
Group Leader Kaja Kristine Selmer, Oslo University Hospital
Summary
Epilepsy is one of the most common neurological diseases, affecting about 65 million people globally. The mainstay of treatment for epilepsy is anti-seizure medications (ASMs). However, 1 in 3 patients do not achieve seizure control with drugs alone. In these patients, high-fat, low-carbohydrate diets, termed ketogenic diets, can be a treatment option. Randomized controlled trials have demonstrated ketogenic diets’ effectiveness in reducing seizures in patients with epilepsy, but the mechanism(s) of action remain elusive.
The aims of this thesis was to investigate the impact of ketogenic diets on DNA methylation, and ASM serum concentrations in patients with epilepsy.
The work in the present thesis is based on two different study populations: 1) adults with drug resistant epilepsy treated with a modified ketogenic diet, and 2) children with drug resistant epilepsy treated with a classical ketogenic diet. In both studies, the patients ate their normal diet in a baseline period, and subsequently a ketogenic diet in a 12-week intervention period.
In adults with epilepsy, DNA methylation decreased significantly following 12 weeks of dietary treatment. A considerable proportion of the genes with altered DNA methylation were associated with epilepsy, regulation of lipid- and glucose metabolism, gene transcription, inositol phosphate metabolism, or basic cell functions. We found no differences in DNA methylation in patients who experienced seizure reduction compared to patients who did not experience any seizure reduction.
In children with epilepsy, serum concentrations of two commonly used ASMs decreased following 12 weeks of treatment with a classical ketogenic diet, indicating potential interactions between the dietary treatment and certain ASMs.
Although the clinical implications of our results are yet to be explored, our findings may provide important clues to understand how ketogenic diets reduce seizures in epilepsy.
Additional information
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