Ketogenic diet for treatment of intractable epilepsy in adults: A meta‐analysis of observational studies

Abstract

SummaryThe ketogenic diet (KD) is an effective treatment for children with drug‐resistant epilepsy and has been widely used in young children. Adult patients with intractable epilepsy would also benefit from this dietary treatment. However, only a few studies have been published, and the use of the KD in intractable epilepsy in adults has been limited. This meta‐analysis summarized the findings of the relevant published studies to identify the efficacy of the KD for the treatment of intractable epilepsy in adults. In this meta‐analysis, PubMed, Embase, and Cochrane Library were used for searching studies concerning the effects of the KD and its major subtypes with intractable epilepsy in adults published up to January 10, 2017. The primary outcomes were seizure freedom, seizure reduction by 50% or more, and seizure reduction by <50%. The quality of the methodology of the observational studies was reviewed by using the Newcastle‐Ottawa Scale. We identified 402 articles, of which, 16 studies including 338 patients met the inclusion criteria. The results of the meta‐analysis showed that the combined efficacy rates of all the symptoms of seizure freedom, seizure reduction by 50% or more, and seizure reduction below 50% in adults with intractable epilepsy were 13%, 53%, and 27%, respectively. The adverse reactions of the KD were mild, whereas low glycemic index diet (LGID) and low‐dose fish oil diet (LFOD) may have fewer side effects. Weight loss, high level of low‐density lipoprotein, and elevated total cholesterol were most frequent. The meta‐analysis indicates that the KD for refractory epilepsy in adults is a well‐tolerated treatment and that its side effects are acceptable, which show that the KD is a promising treatment in adult intractable epilepsy. Further research is needed to assess which type of diet or ratio is more effective in the KD treatment.

Randomized trial of add‐on triheptanoin vs medium chain triglycerides in adults with refractory epilepsy

“…16 Thus, in our small blinded study, the efficacy of the MCT treatment regarding >50% of seizure reduction (45%) is within the CIs of the ketogenic and Atkins diets' effects. The meta-analysis critically evaluated 16 prospective open-label studies with a total of 338 patients showing 62% completion on average in all studies, whereas 56% of 76 patients completed the 5 pure ketogenic diet studies.…”

“…Several studies with ketogenic diet or modified Atkin's diets have found similar antiseizure effects in children 14,15 and often adults 16 (although not consistently 17 ). The seizure frequency reductions in 5 of 11 participants treated with MCTs was encouraging, and, if confirmed, is comparable to other types of diets.…”

“…16 In general, adults have difficulties adhering to the very strict versions of the diet and it can be unsustainable long term. This is very important, as it opens up new possible treatment options for this population.…”

“…Therefore, alternative sources of carbons for the brain, such as medium chain fatty acids or ketone bodies, are needed to address reduced glucose metabolism (reviewed by Ref. 16, but see Ref. Moreover, decreases in brain levels of glutamate, glutamine, and malate have been found in people with epilepsy and in rodent chronic epilepsy models, indicating that the tricarboxylic acid (TCA) cycle is deficient of intermediates containing 4 or 5 carbons.…”

“…[8][9][10][11][12] This decreases the capacity for TCA cycle flux and subsequent ATP, amino acid, and lipid production. 16,19 Here, we investigated for the first time the safety and tolerability of medium chain triglycerides (MCTs, which contain triglycerides with octanoate and decanoate) and triheptanoin (triglyceride of heptanoate) as add-on treatments, because they target the metabolic deficiencies in epilepsy described. 6,12 Few approaches can address these impairments in energy metabolism.…”