Review article
A Systematic Review of the Use of the Ketogenic Diet in Childhood Epilepsy

https://doi.org/10.1016/j.pediatrneurol.2006.01.005Get rights and content

The ketogenic diet has been used in the treatment of intractable childhood epilepsy since the 1920s. A systematic review of the efficacy, adverse reactions, and costs associated with using the diet was performed. PubMed and Ovid searches were performed using the keywords epilepsy/therapy, dietary therapy, ketogenic diet, adverse events, and costs. Cochrane library was searched. Bibliographies of papers located by searches and review articles were compiled. Papers published after 1990 were selected if they were written in either English or French and reported on the use of classic ketogenic diet in patients under age 18 years of age with medically refractory epilepsy. Outcome measures were degree of seizure control, duration patient remained on diet, and occurrence of adverse events. Twenty-six studies were found. No prospective-controlled studies were found. Fourteen studies met all criteria for inclusion. The studies indicated that some children report reduction in seizure frequency. The estimated rate for obtaining complete seizure control was 15.6% (95% confidence interval 10.4-20.8%) with 33% (95% confidence interval 24.3-41.8%) reporting greater than 50% reduction in seizures. Adverse events were not frequent; however, 16 cases of death occurring while on the diet were found. No cost/benefit studies were located. There is evidence to support the cautious use of ketogenic diet in children with refractory epilepsy

Introduction

Fasting has been used in the treatment of epilepsy since Biblical times (Matthew 17:5-21). The first modern reports of its use in the medical literature were by Guelpha in 1911 and Conklin in 1921 [1]. Their hypothesis was that prolonged fasting resulted in detoxification of the gut, resulting in a decrease in the frequency of seizure occurrence. In 1921, Wilder postulated that the antiepileptic effect of the diet was related to the production of ketones and not to starvation [1]. He proposed that increasing the fat content in the diet while reducing the carbohydrate would lead to reduction in seizure frequency. Based on Wilder’s hypothesis, Talbot in 1927 developed a ketogenic diet protocol similar to present-day diet which consisted of a period of fasting followed by the introduction of a 4:1 fat to carbohydrate ratio diet in association with restriction in water intake [1]. With the development of newer antiepileptic drugs with improved efficacy and convenience, there was a significant decrease in the use of the ketogenic diet until recently. With the publicity in the lay press of the case of “Charlie” in 1994, a renewed interest and popularity of the diet has occurred. Several studies since that time have suggested that the diet could be an effective alternative to treatment for children with refractory epilepsy [1]. The purpose of this paper was to review the evidence in the medical literature for the efficacy, safety, and cost of treating a child with the classic form of the ketogenic diet.

Section snippets

Method of Search

A search of the medical literature databases PubMed and Ovid was performed using the keywords “epilepsy/therapy” cross-referenced with the text word “ketogenic diet”, followed by using the keyword “dietary therapy” cross-referenced to text word “epilepsy”. Search for reported adverse reactions while on the ketogenic diet was performed using the same database with keyword “epilepsy” cross-referenced to “toxicity/adverse results” followed by “ketogenic diet”. Search for the cost of treatment

Efficacy of the Ketogenic Diet

Since 1990, a total of 26 studies were identified that meet the above stated criteria [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28]. No papers met the criteria for Class One Evidence. Seventeen papers met the criteria for Class Two Evidence [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19]; however, three of these papers were excluded as

Discussion

To establish the efficacy of a new antiepileptic agent for marketing, it must be demonstrated to decrease the frequency of seizures more than the control in a safe manner [38]. This procedure requires the development of a blinded prospective study using a well-defined cohort and sufficient sample size to demonstrate efficacy of the agent (i.e., Class One Evidence). To date, no studies met the criteria for Class One Evidence for efficacy in the use of ketogenic diet in children with refractory

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