Drug-resistance Epilepsy
Epilepsy is affecting nearly 50 million people worldwide. Several medications are available. However, approximately 1/3 of the patients are drug-resistant and continue to experience seizures. Furthermore, the side effects make the availability of other treatments necessary. Almost half of the patients with epilepsy are looking for other medical therapies to ameliorate the seizure burden and improve quality of life (Sadeghifar & Baute Penry, 2019). The ketogenic diet, a high fat, low protein, low carbohydrate diet has been used as a method for almost 100 years and is accepted as an effective protocol (Williams & Cervenka, 2017). The diet leads to a more than 50% seizure reduction in 36-85% of patients and positively affects cognition (van Berkel, IJff, & Verkuyl, 2018).
The traditional ketogenic diet is, unfortunately, not without side effects. Gastro-intestinal disturbances, micronutrient deficiencies, hypertriglyceridemia and ketoacidosis are some of them. In 1971, the ketogenic diet based on MCTs was introduced (MCT-ketogenic diet). Due to the fact that MCTs are more ketogenic than LCTs, the diet became much more palatable, since less of the calories needed to be consumed from fat (Liu & Wang, 2013). After MCTs have been absorbed in the body via the mechanism described in the introduction, the medium-chain fatty acids (mainly decanoic acid and octanoic acid) are rapidly metabolized by beta-oxidation. Metabolism of these fatty acids results in the generation of three major ketones; beta-hydroxybutyrate, acetoacetate and acetone. Numerous studies (retrospective, prospective and randomized trials) have shown the efficacy of the MCT-ketogenic diet. As a summary, more than 50% of the children showed a decrease of more than 50% in seizures. There are 2 other ketogenic protocols; modified Atkins diet and the low glycemic index treatment. Both methods have been studied less to date.
The biggest benefit of the MCT ketogenic diet is that it is much less strict than the classic ketogenic diet in carbohydrate intake and portion size. (Liu & Wang, 2013). Due to the larger portions and higher variety of food, children have fewer incidents of renal calculi, hypoglycemia, ketoacidosis, constipation, low bone density and growth retardation. In addition, there is a positive effect on lipid and cholesterol levels. The limitation is that in patients taking the medicine valproate, MCTs are not recommended due to reported liver issues. The other limitation is that the MCT ketogenic diet needs to be introduced step by step to avoid GI issues.
A recent review, in Lancet Neurology, is suggesting additional effective mechanisms of action from MCTs besides ketone formation (Augustin, et al., 2018). Ketones are an additional energy source for brain cells that is more efficient than glucose, resulting in beneficial downstream metabolic changes. That was always the hypothesis behind the mechanism of action of a reduction of seizures. It has now also been shown that MCTs can directly change cell energetics by mitochondrial biogenesis and also cause alterations in the glycolysis. This will lead to increased ATP availability and with that an increased seizure threshold.
The numerous publications on the MCT ketogenic diet makes it safe to conclude that MCTs play an important role in seizure reduction in patients suffering from drug-resistant epilepsy. As with the use of medical nutrition in general, careful monitoring by a dietician or clinician is required.