Epilepsy The Ketogenic Diet in the Treatment of Childhood Epilepsy J Helen Cross


The Prince of Wales’s Chair of Childhood Epilepsy, University College London–Institute of Child Health, Great Ormond Street Hospital for Children, and the National Centre for Young People with Epilepsy


Abstract


The ketogenic diet has been used for the treatment of drug-resistant epilepsy in childhood for almost 100 years. This aside, it is only over the past decade that renewed interest has led to a further evidence base for efficacy, evaluation of optimal implementation and wider discussion of possible mechanisms of action. Randomised controlled data have now demonstrated the diet to be as effective as any newer anti-epileptic drug (AED) in drug-resistant epilepsy. Implementation can be challenging, and is resource-intensive, but successful use can lead to improved quality of life with most immediate side effects alleviated by dietary manipulation. However, data are still required on the choice of optimal candidates and the role of alternative diets in older children.


Keywords Ketogenic diet, epilepsy, childhood, drug-resistant


Disclosure: J Helen Cross has received funding from HSA, Smiths Charity, SHS International, Matthews Friends and the Milk Development Council for ketogenic diet studies. The UCL Institute of Child Health received funding as a National Institute for Health and Research Specialist Biomedical Research Centre. Received: 18 May 2010 Accepted: 21 June 2010 Citation: European Neurological Review, 2010;5(1):88–91 Correspondence: J Helen Cross, Neurosciences Unit, UCL–Institute of Child Health, The Wolfson Centre, Mecklenburgh Square, London, WC1N 2AP, UK. E: hcross@ich.ucl.ac.uk


Support: The publication of this article was funded by SHS International Ltd. The views and opinions expressed are those of the author and not necessarily those of SHS International Ltd.


Realising that this was not practical, Wilder in 1921 suggested that designing a diet that may mimic the effects of starvation – namely with fat as the main source of energy that is metabolised to ketones – could consequently have a similar effect on epileptic seizures.4


The ketogenic diet (KD) is a high-fat diet used in the management of childhood epilepsy. It was determined in the early part of last century that starvation could have a beneficial effect on seizure control.1–3


Subsequently, a colleague confirmed the


beneficial effect of the then so-called ‘classic ketogenic diet’.5 Following this, its use became widespread, but with the advent of anticonvulsant medication, in particular phenytoin in the 1930s, its use became less favoured. However, in time it became evident that medication was not the solution for all and there was a resurgence in the popularity of the KD.


The original diet was composed of predominantly long-chain fats and was based on the ratio of fat to carbohydrate and protein (3:1 or 4:1), the so-called classic KD. Over the years it became evident that there was some concern about tolerability. In 1971 Huttenlocher reported on the use of an alternative fat – medium- chain triglyceride (MCT), which is more ketogenic per calorie than long-chain fat – as a supplement, and the MCT diet was born.6 However, of note this diet still remained low in carbohydrate. Subsequent use of the KD has been variable, with consideration in management dependent on the experience of individual professionals. However, the evidence base is now increasing as


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regards benefits of the diet in drug-resistant epilepsies of childhood and, more specifically, particular epilepsy syndromes.


The Evidence Base for Efficacy – Does It Work? Many open-label retrospective and prospective studies have reported on the use of the diet in the treatment of childhood epilepsy. However, the quality of such studies has been variable. In 2000 a systematic review reported on studies evaluating the KD and its use in childhood epilepsy.7


Of note was the fact that only 11 studies


fulfilled the criteria for the review. All 11 were observational, only two had been carried out on a prospective basis and nine out of the 11 were from a single institution. Since then there has been a steady increase in the number of publications from both a clinical and a basic science perspective. A further systematic review in 2006 of articles since 1990 found only 26 studies, 14 of which met the criteria for inclusion, which included up to six-month outcome data on the diet.8 There were 17 Class Two studies that could be included. This gave a total collective population of 972 children. At six months, 15.6% were seizure-free and 33% had more than a 50% reduction of seizures. However, it was also emphasised that there were no randomised controlled data and the author stated that these were desperately needed in order to verify the effect of the diet in line with assessment of anti-epileptic medications.


More recently, the first randomised controlled trial was published of use of the KD in drug-resistant epilepsy in childhood.9


This © TOUCH BRIEFINGS 2010


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