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Ketogenic diet for the treatment of pediatric epilepsy: review and meta-analysis

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Abstract

The ketogenic diet (KD), containing high levels of fat and low levels of carbohydrates, has been used to treat refractory epilepsy since the 1920s. In the past few decades, there has been more interest in less restrictive KDs such as the modified Atkins diet (MAD).

Purpose

Our aim was to review all evidence regarding the efficacy and tolerability of the KD and MAD from randomized controlled trials (RCTs) in children and adolescents with refractory epilepsy.

Methods

We reviewed the current literature using Cochrane, EMBASE, and MEDLINE (using PubMed). We implemented predefined criteria regarding dataextraction and study quality.

Results

We identified five RCTs that generated seven publications and recruited 472 children and adolescents with refractory epilepsy (≤ 18 years). The primary outcome (seizure frequency reduction (SFR) ≥ 50%) was attained in 35–56.1% of the participants in the intervention group, compared with 6–18.2% in the control group. Our meta-analysis underlined the significant efficacy of the KD compared with the control group: RR = 5.1 (95% CI 3.18–8.21, p < 0.001). Additionally, only two studies mentioned possible biomarkers to objectively evaluate the efficacy. Secondary outcomes, such as seizure severity and quality of life, were studied in three trials, leading to indecisive generalization of these findings. Gastro-intestinal adverse effects were the most prevalent, and no severe adverse effects were reported.

Conclusion

Despite the heterogeneity between all studies, the beneficial results underline that dietary interventions should be considered for children and adolescents with refractory epilepsy who are not eligible for epilepsy surgery. Future studies should be multi-center and long-term, and evaluate potential biomarkers and adverse effects.

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Acknowledgments

We would like to thank Dr. Adri Voogd for his supportive comments on the manuscript.

Funding information

LL receives research funding, speakers, and advisory board honoraria: Zogenix, UCB, Shire, Novartis, Eisai.

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Authors and Affiliations

  1. Department of Development and Regeneration, Section Pediatric Neurology, University Hospital KU Leuven, Herestraat 49, box 7003 20, 3000, Leuven, Belgium

    Jo Sourbron & Lieven Lagae

  2. Kempenhaeghe Centre for Neurological Learning Disabilities, Heeze, the Netherlands

    Sylvia Klinkenberg

  3. Department of Neurology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands

    Sylvia Klinkenberg & Marian Majoie

  4. Department of Epidemiology and Medical Technology Assessment (KEMTA), Maastricht University, Maastricht, the Netherlands

    Sander M. J. van Kuijk

  5. Department of Neurology, Academic Center for Epileptology, Kempenhaeghe & Maastricht UMC+, Heeze, Netherlands

    Danielle Lambrechts & Marian Majoie

  6. Department of Pediatric Neurology, Amalia Children’s Hospital, Radboud University Medical Center & Donders Institute for Brain, Cognition and Behavior, Nijmegen, Netherlands

    Hilde M. H. Braakman

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  1. Jo Sourbron
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Correspondence to Jo Sourbron.

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JS, MM, HB, SK, SvK, and DL declare no conflict of interest

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Sourbron, J., Klinkenberg, S., van Kuijk, S.M.J. et al. Ketogenic diet for the treatment of pediatric epilepsy: review and meta-analysis. Childs Nerv Syst 36, 1099–1109 (2020). https://doi.org/10.1007/s00381-020-04578-7

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