Dietary Treatments for Epilepsy: Why is this So Hard for Us to Swallow?

Commentary

Dietary treatments are the oldest known effective treatment for epilepsy. Prolonged periods of fasting and starvation were used to reduce seizure frequency since the Hippocrates era, 5000 BC (1). A significant resurgence began in the 1920s and 1930s when the use of diets for epilepsy became mainstream, and significant reduction in seizure frequency was reported in early case series (1). However, the advent of antiseizure medications brought a drop of interest in dietary treatments; it was not until after the year 2000 that interest reemerged and flourished with the development of dietary clinics and teams within pediatrics, and more recently, adult epilepsy care settings.

Dietary treatments for epilepsy (DTE) include a group of dietary regimes that have in common a significant carbohydrate restriction and a very generous fat intake as compared with the standard American diet and “heart-healthy diets,” which are usually rich in complex carbohydrates. The different dietary treatments used for epilepsy vary, according to the proportion of fat to nonfat intake in grams, for a given day. The classic ketogenic diet (KD) observes a 4:1 or 3:1 proportion of fat to nonfat intake (carbohydrates and proteins combined) and represents a daily carbohydrate load of less than 5 g/day. The modified Atkins diet (MAD) is a less restrictive version of these DTE. It observes a 2:1 ratio and allows for net carbohydrate intake of 10 g/day in children and 15 g/day in teens and adults. A third alternative is the much less restrictive low glycemic index diet (LGID), which limits the net carbohydrate intake to 40–60 g, as long as the carbohydrates consumed have a very low glycemic index, which means a low or delayed effect in blood glucose level following the ingestion of each particular food. All of the DTE require a strict restriction of sugar and simple carbohydrate intake, encourage proper hydration, observe adequate electrolyte/mineral replenishment, and are meant to support adequate, not increased, protein consumption.

Studies of the KD have proven that it is efficacious for the treatment of refractory epilepsy, consistently showing better than 50% seizure reduction in around 50% of patients (2); however, it is often used only in the most aggressive subset of the epilepsy cases, as it is considered to be very difficult to implement and sustain. It is offered only as a last resort for super-refractory cases. The main limitation for the use of this diet in particular is the need for strong parental involvement, weight measurement, and strict control over all food intake. It has been postulated that an important limitation for its use is the physician perception of how difficult the diet is to implement.

Dr. Kim et al. set themselves to compare the efficacy of the less restrictive MAD, which allowed for 10–15 g carbohydrates per day, to the classic KD (4:1 ratio) for the treatment of refractory epilepsy in a cohort of children aged 1 to 18 years, with a relatively high seizure frequency of more than four seizures a month. They showed excellent results in both groups with regard to seizure reduction at 3 and 6 months and even seizure freedom in 53% of patients on KD and 20% of patients on MAD at 3 months after starting the diet. The KD demonstrated superior efficacy in the group of patients younger than 2 years old. In children older than 2 years, both diets had comparable efficacy. The side-effect profile was similar but slightly more benign in the MAD group.

Similar results have been reported for KD and MAD (3), consistently showing efficacy of greater than 50% seizure reduction in 30 to 50 percent of patients sustained over long-term follow-up (up to 4 years) (3), with reasonable long-term adherence to the treatment and a favorable safety profile. Even the less restrictive LGID has shown similar efficacy results in children and adult populations (4, 5). These results are comparable to the efficacy of any medication treatment; which makes it hard to understand why the DTE are not more widely recommended to our patients? What is preventing us from giving dietary advice to our patients more widely? It may actually be our own bias; our own perception that a dietary regime is too difficult to follow or the belief that our patients are more likely, or more willing, to take more pills than to learn a new way of health-promoting eating.

The implementation of KD, MAD, or LGID requires the close involvement of a dietitian working with the epilepsy team. The introduction to the treatment entails educating the patient and the family regarding nutrition and the metabolic basis for the DTE. A comprehensive nutritional consultation, ongoing support, and even cooking/shopping advice are part of the program. Patients following the MAD and the LGID eat a less-extreme diet than their doctors imagine, consisting of non-starchy vegetables, nuts, animal protein, high-fat diary, and multiple sources of fat.

The MAD and LGID are safe and well tolerated by older children, adolescents (6), and adults; while the classic KD continues to be the dietary treatment of choice for children under 2. The DTE can be used by most of our patients regardless of health insurance concerns; they can be adapted to different budgets and even accommodate other eating restrictions or preferences such as vegetarian and gluten-free. They have minimal interactions with antiepileptic medications and fewer side effects. In our clinic, dietary therapies have shown a positive impact on quality of life.

Many of our patients welcome DTE as a way to get control of their own treatment and make healthier lifestyle choices. And, there is even more to this argument as publications outside of the epilepsy literature start to highlight potential benefits of low-carbohydrate, high-fat diets in the management of patients with metabolic syndrome, insulin resistance, diabetes, and obesity (7, 8). Hyperlipidemia is a common transient side effect of these types of diets, which reverses over time and tends to transition to a high-HDL, low-triglyceride lipid profile in most patients, which, together with weight loss and better diabetes control, may contribute to lower vascular risk factors (9) under adequate supervision.

Given the multiple potential benefits described, we expect DTE to become part of our everyday epilepsy treatment. By not offering them as part of a comprehensive strategy, we may be doing a disservice to our patients. Dietary treatments have shown what they can do. It is now time we dare to swallow them.