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Inflammation and oxidative stress in epileptic children: from molecular mechanisms to clinical application of ketogenic diet

  • Azam Ildarabadi , Seyedeh Nooshan Mir Mohammad Ali , Fatemeh Rahmani , Narjes Mosavari , Elham Pourbakhtyaran and Nima Rezaei EMAIL logo
Published/Copyright: February 14, 2024
Become an author with De Gruyter Brill

Abstract

Childhood epilepsy affects up to 1 % of children. It has been shown that 30 % of patients are resistant to drug treatments, making further investigation of other potential treatment strategies necessary. One such approach is the ketogenic diet (KD) showing promising results and potential benefits beyond the use of current antiepileptic drugs. This study aims to investigate the effects of KD on inflammation and oxidative stress, as one of the main suggested mechanisms of neuroprotection, in children with epilepsy. This narrative review was conducted using the Medline and Google Scholar databases, and by searching epilepsy, drug-resistant epilepsy, child, children, ketogenic, ketogenic diet, diet, ketogenic, keto, ketone bodies (BHB), PUFA, gut microbiota, inflammation, inflammation mediators, neurogenic inflammation, neuroinflammation, inflammatory marker, adenosine modulation, mitochondrial function, MTOR pathway, Nrf2 pathway, mitochondrial dysfunction, PPARɣ, oxidative stress, ROS/RNS, and stress oxidative as keywords. Compelling evidence underscores inflammation and oxidative stress as pivotal factors in epilepsy, even in cases with genetic origins. The ketogenic diet effectively addresses these factors by reducing ROS and RNS, enhancing antioxidant defenses, improving mitochondrial function, and regulating inflammatory genes. Additionally, KD curbs pro-inflammatory cytokine and chemokine production by dampening NF-κB activation, inhibiting the NLRP3 inflammasome, increasing brain adenosine levels, mTOR pathway inhibition, upregulating PPARɣ expression, and promoting a healthy gut microbiota while emphasizing the consumption of healthy fats. KD could be considered a promising therapeutic intervention in patients with epilepsy particularly in drug-resistant epilepsy cases, due to its targeted approach addressing oxidative stress and inflammatory mechanisms.


Corresponding author: Nima Rezaei, Network of Interdisciplinarity in Neonates and Infants (NINI), Universal Scientific Education and Research Network (USERN), Dr. Qarib St, Tehran 1419733151, Iran; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Dr. Qarib St, Tehran 1419733151, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Science, Pour Sina St, Tehran 1461884513, Iran; and Research Center for Immunodeficiencies, Children’s Medical Center Hospital, Dr. Qarib St, Keshavarz Blvd, Tehran 14194, Iran, E-mail:

Acknowledgment

We would like to thank Dr. Noosha Samieefar for her invaluable comments on our manuscript.

  1. Research ethics: Not applicable.

  2. Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: The authors state no conflict of interest.

  4. Research funding: None declared.

  5. Data availability: Not applicable.

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Received: 2023-10-15
Accepted: 2023-12-18
Published Online: 2024-02-14
Published in Print: 2024-06-25

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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