Abstracts

The ketogenic diet (KD) is a 90% fat, 10% protein and carbohydrate diet that mimics prolonged fasting by creating a state of metabolic ketosis and is an effective treatment of intractable epilepsy in children. The implementation and management of the KD requires significant time and financial resources and has changed little since its inception in 1921. The authors hypothesized that a gradual introduction is as effective as the standard 24-48 hour fasting introduction to the KD. Children ages one to 14 with intractable epilepsy were randomized to begin the KD using either a fasting (FAST-KD) or gradual (GRAD-KD) protocol. Both protocols were implemented during a 6-day inpatient admission. The FAST-KD protocol began with a [lt] 48 hour fast. The the 4:1 ratio (fat: carb + protein) meal was then advanced in 1/3 caloric increments over 3 days until the full meal was tolerated. The GRAD-KD protocol began without a fast, with three full calorie meals at a 1:1 ratio. The ratio of the meal was then advanced daily to a 2:1, 3:1 and finally 4:1 ratio. Seizure records were collected 28 days before the admission and for the 3-month duration of the study. Subjects were evaluated at 0.5, 1, 2 and 3 months follow up. Effectiveness was measured as % reduction in target seizure type from baseline to the 3 months evaluation. 48 subjects were randomized, 24 into each protocol. In the FAST-KD group 58% had [gt]50% reduction in the target seizure at 3 months and 21% were seizure free. In the GRAD-KD protocol 67% had a [gt]50% reduction in the target seizure type at 3 months and 21% were seizure free.
Based on the proportions of subjects with 50% reduction at 3 month, a one sided test of equivalence of proportions for two independent groups, with equivalence limit difference set at 20%, resulted in a p-value of 0.0325, indicating that the two protocols are equivalent.
At 3 months, the mean % reduction rate for the FAST-KD protocol was 56.3 (SD = 54.6), while for the GRAD-KD protocol, the mean % reduction rate was 56.9 (SD = 72.1). Based on logarithmic transformed percent reduction rate, a one sided test of equivalence of means for the two independent groups with an equivalence limit difference set at 20%, resulted in a p-value of 0.0002, indicating that the two protocols are equivalent. These data suggest that a gradual introduction of the KD does not decrease the effectiveness of the KD in children 1-14 years of age. (Supported by RR K-23 16074, General Clinical Research Center MO1RR00240, Nutrition Center, and a private donation by Ms.Catherine Brown.)