The Effects of Ketogenic Diet On Beta-Hydroxybutyrate, Arachidonic Acid, and Oxidative Stress In Pediatric Epilepsy

Objectives: The exact mechanism of ketogenic diet (KD) as a suitable alternative therapeutic approach for drug-resistant epilepsy (DRE) in alleviating seizures is not yet fully understood. The present study aimed to evaluate the role of the KD in reducing oxidative stress by increasing the ketone body beta-hydroxybutyrate (BHB) and Arachidonic acid (ARA), an essential polyunsaturated fatty acid, as a possible mechanism in relieving seizure attacks in children with DRE.

Methods: Forty children with refractory epilepsy were included in the present study. The serum levels of BHB, ARA, and oxidative stress markers, malondialdehyde (MDA) and 8-hydroxyl-deoxyguanosine (8-OHdG), were evaluated in children with DRE and compared before and after the six months of KD therapy.

Results: 34 of 40 included children could complete the six-month KD therapy. 21 (61.76%) patients had more than 50% reduction in the seizure frequency after the KD (responders). The remaining 13 children were considered as non-responders to the diet. The serum levels of ARA and BHB significantly (p<0.05) increased after the KD therapy. The serum levels of oxidative stress parameters MDA and 8-OHdG before the diet therapy were significantly (p<0.05) higher than those after the administration. The serum levels of BHB and MDA after the KD therapy in the responders were respectively higher and lower than those in the non-responders (p<0.001).

Conclusion: KD might reduce brain oxidative stress by increasing BHB and ARA. The role of BHB in diminishing oxidative stress and seizure might be more remarkable than ARA.