Effect of the ketogenic diet as a treatment for refractory epilepsy in children and adolescents: a systematic review of reviews

Context: Epilepsy is one of the most prevalent neurological disorders in childhood. Antiepileptic drugs are the preferred treatment. However, 30% of children continue suffering seizures. A ketogenic diet (KD) is one of the emerging alternative treatments.

Objective: This review aims to analyze the current evidence regarding the use of a KD for the treatment of refractory epilepsy (RE) in childhood.

Data sources: A systematic review of reviews was performed, based on MEDLINE (PubMed) as at January 2021.

Data extraction: The data extracted included the first author's last name; the year of publication; the country; the study design; the population; the diagnosis, concept, and description of KD types; and major outcome.

Results: Twenty-one reviews were included, 8 with systematic methodology (2 of them included a meta-analysis) and 13 with unsystematic methodology. The main difference between the 2 types of reviews is the reproducibility of their methodology. Therefore, the results of each type of review were analyzed separately. Each type of review described 4 categories of KD: classic KD, modified Atkins diet (MAD), use of medium-chain triglycerides (MCTs), and low glycemic index treatment (LGIT). In terms of effectiveness, the considered systematic reviews reported reductions in the frequency of seizures greater than 50% in about half of the patients. Reviews without systematic methodology reported that 30%-60% of the children showed a 50% or greater reduction in seizures. The most frequently described adverse effects in the 8 systematic reviews were: vomiting (6/8), constipation (6/8), and diarrhea (6/8); and in the unsystematic reviews: vomiting and nausea (10/13), constipation (10/13), and acidosis (9/13).

Conclusion: KD can be an effective treatment for RE, with a more than 50% reduction in the frequency of seizures and cognitive improvement being achieved in half of the pediatric patients. The effectiveness of the various types of KD is comparable, and the KD can be adapted to the needs of the patient.

Systematic review registration: PROSPERO registration no. CRD42021244142.