Ketogenic diet in pediatric seizures: a randomized controlled trial review and meta-analysis

ABSTRACT

Background

The ketogenic diet is a non-pharmacologic treatment option for children with drug-resistant epilepsy. This systematic review and meta-analysis aimed to assess the efficacy of the ketogenic diet on seizures frequency in children.

Methods

We reviewed the literature using Cochrane, EMBASE, MEDLINE, and highly qualified journals.

Randomized controlled trials were chosen to investigate the seizures-free regime or at least 50% seizures reduction after three months from the starting of the ketogenic diet or earlier. We have selected articles from January 2011 to January 2020.

Eight articles were eligible. The data show a significant reduction in seizure frequency in the dietary treatment pediatric population. The rate of a seizures-free regime or at least 50% seizures reduction was 48.31% of patients in the intervention group.

Results

Our overall meta-analysis underlined the significant efficacy. The KD group is 5.6 times more likely than the control group to have a 50% reduction of seizures after three months of the diet or earlier.

QUADAS and AMSTAR assessments showed a low risk of bias and adequate accuracy.

Conclusion

The results show that the KD reduces seizure frequency in children with drug-refractory epilepsy. KD is an effective treatment option for children and adolescents with refractory epilepsy.

KEYWORDS:

• Children- pediatric- infant-childhood - epilepsy - ketogenic – diet-seizure- treatment

Article highlights

• Epilepsy is the most prevalent chronic neurologic disease in childhood.

• Ketogenic diet is a non-pharmacologic treatment option for children with drug resistant epilepsy.

• The aim of this systematic review and meta-analysis was to assess the efficacy of the ketogenic diet on seizures frequency in children.

• Eight articles were included. The data show a significant reduction in seizure frequency in the dietary treatment in pediatric population.

• The rate of seizures-free regime or at least 50% seizures reduction was 48.31% of patients in the intervention group compared to the control group.

• The results show that the KD reduces seizure frequency in children with drug-refractory epilepsy. KD and variations of this diet (e.g. MAD) are effective as a treatment option for children and adolescents with refractory epilepsy.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

The work was distributed, and all authors contributed equally to the creation of the manuscript. During the writing of the article, periodic briefings were held in which all the authors informed each other about the development of the specific issues. F Pizzo edited the chapter on materials and methods and contributed to the statistical analysis. AD Collotta dealt with the evaluation of the quality and limitations of the selected articles. A Di Nora has been involved in studying the literature on the topic addressed in the article and assessing which precedents were present in the literature to create a work as original as possible. G Costanza evaluated the development of the ketogenic diet guidelines over time and the latest developments. M Ruggieri led the whole team of authors trying to divide the work and indicating within which parameters of scientific rigor to develop the research. R Falsaperla guided the authors with his practical experience in the ketogenic diet. It also coordinated the changes to be made during the review work.

Author contributions section

The work was distributed, and all authors contributed equally to the creation of the manuscript. During the writing of the article, periodic briefings were held in which all the authors informed each other about the development of the specific issues.

FP edited the chapter on materials and methods and contributed to the statistical analysis.

ADC dealt with the evaluation of the quality and limitations of the selected articles.

ADN has been involved in studying the literature on the topic addressed in the article and assessing which precedents were present in the literature to create a work as original as possible.

GC evaluated the development of the ketogenic diet guidelines over time and the latest developments.

MR led the whole team of authors trying to divide the work and indicating within which parameters of scientific rigor to develop the research.

RF guided the authors with his practical experience in the ketogenic diet. It also coordinated the changes to be made during the review work.