An Open-label Evaluation of KetoCal in Initial Combination With the Modified Atkins Diet for the Treatment of Intractable Childhood Epilepsy

The modified Atkins diet (MAD) is a treatment for intractable epilepsy that has been used in over 100 children and adults worldwide since 2002. It mimics the ketotic state of the ketogenic diet (KD), yet does so without fluid, calorie, or protein restriction, and without the need for an inpatient admission or fasting period. Children are started on a daily allotment of 10 grams of carbohydrates per day, with gradual increases to 20-30 grams per day after several months. To date, six studies have demonstrated the MAD as effective, with approximately 50% of patients having at least a 50% reduction in their seizure frequency. The MAD works relatively quickly, with beneficial results when present, within 2-4 weeks.

Over the past 5 years since its introduction, our center and others have researched methods to make the MAD both more tolerable and efficacious. Important clues came in 2007, in which an initial carbohydrate limit of 10 grams per day was compared to 20 grams per day in a randomized , prospective, crossover design. Although the hypothesis was that these two carbohydrate limits were equivalent, this was only true after the 3-month crossover period. At diet onset, there was a significantly higher likelihood of a >50% seizure reduction when a stricter, 10 grams/day MAD was used (60% vs. 10%, p=0.03). Ketosis was higher in that group at 1 month as well, similar to previous findings that the 1-month ketosis levels correlated with efficacy. These results suggested that a stricter, higher ketotic, start to the MAD was important - although loosening restrictions after 1-3 months was also reasonable and did not adversely affect seizure control.

That same year, a research study from South Korea evaluating the initial ratio (3:1 vs. 4:1) of the traditional ketogenic diet in a similar randomized, crossover design found identical results. A 4:1 initial ketogenic diet ratio was correlated with a higher likelihood of seizure freedom (55% vs. 31%, p<0.05), although ketosis at 3 months was not different. After 3 months, reducing to 3:1 did not lead to reduced seizure control in any of their children.

Recent results using the KD from our center and Chicago Memorial also confirm that the initial month of the KD may be the most crucial. In this study of 99 children on the traditional KD, nearly 90% of children who do respond to the KD do so within the first 28 days. This study suggests that early KD titration to improve efficacy is important.

The results from all of this data within the past year all confirm that the first month of either the MAD or KD may be the most critical. In addition, there is some suggestion that higher ketone levels at 1 month do correlate with better seizure reduction. Therefore, a strict, highly ketotic initial month of dietary therapy may result in better seizure reduction. Realizing that loosening of restrictions will automatically occur after one month, this "tough month" approach is likely to be followed in a compliant manner by most parents knowing it is time-limited.