This study will assess the effectiveness of the ketogenic diet (high-fat, low-carbohydrate, and moderate protein) in treating epilepsy. Two study groups will be comprised of children with epilepsy (0-18 years of age) and whether or not they receive the ketogenic diet - epilepsy/ketogenic diet and epilepsy/non-ketogenic diet.

According to an evidence-based guideline on the diagnosis and management of epilepsy from the National Institute for Clinical Excellence (2012), the ketogenic diet may be considered as an adjunctive treatment in children with drug-resistant epilepsy. Vast anecdotal and Class 1 studies have confirmed that the ketogenic diet helps most children with intractable seizures and cures many. Dietary therapies for epilepsy (e.g., classic ketogenic diet) have been shown to be highly effective. For example, Lee (P.R.) and Kossoff reported that approximately 50% of children with drug-resistant epilepsy had a greater than 50% reduction in seizures within days to months of treatment. In addition, use of the ketogenic diet as a treatment for epilepsy has been shown to reduce the escalating costs associated managing poorly controlled seizures (e.g., decrease in outpatient and emergency visits, inpatient hospitalization, neuroimaging, electro-encephalography, lab testing, and medication use).

If a child's seizures continue after two to three seizure medications have been tried, the ketogenic diet should be considered. However, many parents still medicate their children well beyond these guidelines and tolerate seizure frequency because they have no other alternatives. Given the physical and emotional toll that recurring seizures exact upon these children/families, the potential for improvement with the ketogenic diet is substantial. However, the ketogenic diet remains unavailable to most children.

Approximately 1% of Hawaii's children are projected to have epilepsy, but there is no established, ketogenic diet program for them to receive this dietary intervention, which can incorporate culturally distinct foods to improve palatability and compliance. Although the ketogenic diet has shown promise for broadening the scope of therapeutic options for children with epilepsy, it requires further study in an ethnically diverse population. At Shriners Hospitals for Children-Honolulu, the investigators have initiated a ketogenic and related dietary (e.g., modified Atkins diet) intervention program for children with epilepsy and started to assess its efficacy in treating epilepsy/seizures. This program also includes educational seminars and services to patients residing on the other Hawaii islands through outreach trips. The investigators have begun to enroll children with epilepsy into two groups based on whether or not they receive the ketogenic diet - epilepsy/ketogenic diet and epilepsy/non-ketogenic diet; total estimate of 15-30 participants over three years. Based upon initial findings, the investigators will implement a comprehensive, multidisciplinary ketogenic diet program that will potentially reach hundreds of children throughout Hawaii, the Pacific Basin, and elsewhere.

Specific Aims:

Aim 1. To assess the therapeutic efficacy of the ketogenic diet on epilepsy/seizures.

Hypothesis: Participants who have epilepsy/on the ketogenic diet will have significantly decreased number and severity of seizures than those that are not on the ketogenic diet, between baseline to three and six months after the dietary intervention is initiated.

Aim 2. In anticipation of lessened epilepsy/seizures, to determine the (a) change in number and dose of seizure medications used, (b) change in number of lab tests ordered for epilepsy management, (c) change in number of emergency room and hospital visits for seizures (or other neurodevelopmental problems), (d) change in number of neurologic procedures for epilepsy management (e.g. EEG, MRI, CT), and (e) participant/family satisfaction with the ketogenic diet.

Hypothesis: The number and/or dosage of medications, lab tests ordered, emergency room or hospital visits, and neurologic procedures for epilepsy management will decrease, and participant/family satisfaction will be high for participants who have epilepsy/on the ketogenic diet than those that are not on the ketogenic diet, between baseline to three and six months after the dietary intervention is initiated.

Aim 3. To compare differences and/or changes in (a) serum and urine ketone levels and (b) biochemical profiles as defined from blood and stool (gut or fecal microbiome) specimen samples.

Hypothesis: Participants who have epilepsy/on the ketogenic diet will have significantly higher serum/urine ketone levels and notably different biochemical profiles than those that are not on the ketogenic diet, between baseline to three and six months after the dietary intervention is initiated.

Children helped by the ketogenic diet are more likely to reach their highest level of functioning and become contributing adults. By providing the ketogenic diet as an intervention therapy for epilepsy in a safe and data-driven manner, the community-at-large will benefit and medical knowledge concerning dietary treatment for neurodevelopmental disorders will be advanced.

Inclusion Criteria:

• Ages 0-18 years.
• Primary diagnosis of epilepsy.
• Parent/legal guardian and child able to read or understand English, and able/willing to provide informed consent/assent.
• Females of childbearing potential must have a negative pregnancy test result and agree to use a medically acceptable method of contraception throughout the entire study period and for 30 days after the last dose of study drug - childbearing potential is defined a girls who are > Tanner stage 2 and urine pregnancy tests are acceptable.

Exclusion Criteria:

• Known cardiac disorder including arrhythmias or hypertension.
• Carnitine deficiency (primary).
• Carnitine palmitoyltransferase (CPT) I or II deficiency.
• Carnitine translocase deficiency.
• Beta-oxidation defects - medium-chain acyl dehydrogenase deficiency (MCAD), long-chain acyl dehydrogenase deficiency (LCAD), short-chain acyld dehydrogenase deficiency (SCAD), long-chain 3-hydroxyacyl-coenzyme A (CoA) deficiency, and medium-chain 3-hydroxyacyl-CoA deficiency.
• Pyruvate carboxylase deficiency.
• Porphyria.
• Inability to maintain adequate nutrition.
• Patient or caregiver non-compliance.