The Effect of Ketogenic Diet on Expression of Permeable-Glycoprotein, Multidrug Resistance Protein-1 and Histone Deacetylase-2 in Childhood Drug-Resistant Epilepsy

Objective: To evaluate the expression of efflux-pump proteins such as p-glycoprotein, multidrug resistance protein-1 (MRP-1), and histone deacetylase (HDAC-2, keeps chromatin in condensed form and impairs protein synthesis) on peripheral blood mononuclear cells in children with ketogenic diet and to compare the pre- and postdiet expression of these biomarkers in ketogenic diet responder and nonresponder children. Methods: This prospective observational study included children with drug-resistant epilepsy from April 2019 to July 2023. Baseline clinical data, seizure frequency, antiseizure medication type, number and dose, P-glycoprotein, MRP-1, and HDAC-2 levels were measured before starting ketogenic diet. Antiseizure medications were not modified during the study period. After 3 months of diet, the percentage changes in pre- and postdiet biomarker levels were compared between responders and nonresponders. Results: Thirty participants (mean age 5.41 ± 4.89 years) completed the study. Eighteen patients (60%) ( p < 0.01) experienced ≥ 50% reduction in seizure (responders). The median (interquartile range) percentage change in P-glycoprotein was 47.17 (42.84–51.78) among responders and 22.26 (8.7–43.32) among nonresponders (P = 0.002). For MRP-1, the values were 51.01 (44.07–53.88) for responders and 28.01 (11.07–34.71) for nonresponders ( p < 0.001). HDAC-2 levels changed by 48.95 (42.47–51.73) in responders and 25.93 (14.13–43.04) in nonresponders ( p = 0.001). The most frequent adverse effects were constipation, increased thirst, hypoglycemia, and fatigue. Conclusion: The ketogenic diet was associated with reduced expression of efflux proteins and HDAC-2, which may contribute to improved antiseizure medication effectiveness, suggesting a possible new mechanism of ketogenic diet in drug-resistant epilepsy. Publication History Article published online: 15 July 2026 © 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Private Limited A-13A, Graphix Tower 1, 6th floor, Sector 62, Noida 201309, Uttar Pradesh, India