Pediatric Intractable Epilepsy - Is a Ketogenic Diet an Effective Treatment?
The Question
What is the efficacy of following a ketogenic diet (classic, medium chain triglyceride, low glycemic index treatment or modified Atkins diet) in the treatment of pediatric intractable epilepsy?Recommendation
All types of ketogenic diets (classic, medium chain triglyceride (MCT), low glycemic index treatment (LGIT) and modified Atkins diet (MAD)) have been shown to reduce seizure frequency and improve the likelihood of achieving seizure freedom in children with intractable epilepsy.
The classic ketogenic diet (KD) and MAD have been studied most rigorously. The classic KD may have a larger effect than the MAD, while the MAD may have fewer side-effects. The MCT and LGIT are less well studied but appear efficacious, with the MCT having shown similar efficacy to the classic KD.
In infants <2 years, the classic KD has been recommended. Adolescents may do better with the MAD or LGIT, which are easier to follow and have better adherence.
Evidence Summary
A 2022 systematic review and meta-analysis of eight RCTs (n=453) found that children and adolescents with intractable epilepsy who followed a KD were more likely to reduce their seizure frequency by >50% than those who did not follow a KD. Only the classic KD and the MAD were examined.
A 2020 Cochrane review of 13 RCTs/quasi-RCTs (n=932) found that KDs could be effective in reducing seizures and achieving seizure freedom in children with intractable epilepsy, although the evidence is low or very low quality. Specifically, the classic KD and MAD showed potential efficacy, with a larger effect associated with the classic KD (seizure freedom in up to 55% of individuals compared to 25% for MAD, and reduced seizure frequency in up to 85% of individuals compared to 60% for MAD). However, fewer side-effects were associated with the MAD. Only one study compared the classic KD to the MCT, which found no significant differences in seizure reduction between the two diets. The LGIT was not examined in any included studies.
A 2018 expert consensus statement noted that the classic KD was most appropriate in children <2 years, while the MAD or LGIT were more appropriate in adolescents due to increased adherence. Although no studies have compared the LGIT to other ketogenic diets, it has shown promise in children with intractable epilepsy, especially those with Angleman syndrome. The MCT appears equivalent in efficacy to the classic KD while allowing for higher carbohydrate and protein intakes and a larger variety of food choices.
Grade of Evidence C
Remarks
The classic KD is defined as a diet with high lipid to non-lipid ratio. The MCT is defined as a diet with 60% of calories coming from MCT oil; alternatively, if this is not tolerated due to gastrointestinal side-effects, a lower dose of MCT oil (30-50% calories) may be used.
The MAD is a high fat, low carbohydrate diet focusing on fat and carbohydrate targets rather than ratios. The LGIT allows 45-60 grams of carbohydrate daily but requires that all carbohydrates have a glycemic index <50.
If a child requires a special dietary formulation, ketogenic liquid formula can be provided. Liquid diet formulations can be used in infants or in children with feeding tubes and have the benefit of increased compliance compared to whole food KDs.
See Additional Content: Nervous System – Pediatric/Paediatric Epilepsy: Ketogenic Diet Background.
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