Following a ketogenic diet reduced mean seizure frequency by 38% in a group of children with treatment-resistant epilepsy, according to findings from a first-of-its-kind study.
“Throughout the 20th century, the reports of the effects of the [ketogenic] diet have been limited to case series and retrospective and prospective observational studies,” wrote Dr. Max Wiznitzer of the division of pediatric neurology at the Rainbow Babies and Children's Hospital, Cleveland, in a commentary accompanying the study.
The ketogenic diet establishes a very high-fat, low-carbohydrate regimen, with controlled amounts of protein. There are two versions, both of which were included in this study: the classic, (or LCT, for long-chain triglycerides) version, which has a 3:1 or 4:1 ratio of fat to protein and carbohydrates. A modified version, the MCT, uses medium-chain triglycerides and a slightly lower ratio of fat to carbohydrates and proteins.
In both versions, the fat content was gradually increased from day 1 until the maximum ratio was achieved (by 2 weeks in the LCT version and by 10 days in the MCT). All diets were supplemented with vitamins and minerals, and the children's other treatments were not changed.
In all, 145 patients were enrolled from two U.K. epilepsy clinics to follow a version of the ketogenic diet. The children all had at least one seizure per day or more than seven seizures per week; had not responded to at least two antiepileptic drugs; and had not ever followed a ketogenic diet, wrote Elizabeth G. Neal, Ph.D., of the Institute of Child Health and Great Ormond Street Hospital for Children, London, and colleagues. Patients were aged 2–16 years.
In all, 73 patients were randomly assigned to the diet group; however, 8 did not receive treatment for a variety of reasons, 1 was excluded for inadequate data, and 10 discontinued the diet before the 3-month follow-up, which was the end of the study, leaving 54 patients to be included in the final analysis.
Of the 72 patients initially randomized to the control group, 8 elected not to participate in the study or were not included for other reasons (death, change in diagnosis, or improvements in seizures) and 15 patients were ultimately excluded because of inadequate data, leaving 49 included in the final analysis.
Twice-daily urine tests assessed ketosis. Follow-up visits occurred at 6 weeks and at 3 months (the end of the study). Monitoring also took place via phone.
“The difference between the mean percentage of baseline seizures at 3 months in the diet and control groups was 74.9% (95% confidence interval, 42.4%–107.4%; P less than .0001),” wrote the authors. In addition, one child in the diet group and none in the control group attained complete freedom from seizures (Lancet Neurol. 2008 May 3 [Epub doi:10.1016/S1474–4422(08)70092–9]).
A total of 28 children in the diet groups (38% of the original 73 patients who were randomized) had a greater-than-50% decrease in seizures, compared with 4 in the control group (6% of the original 72 children who were randomized).
A similar magnitude of improvement was seen in children who had symptomatic generalized epilepsy and in those who had focal epilepsy syndromes, both of whom were represented in the study.
Withdrawal from the treatment group resulted from parental unhappiness with the restrictions (three cases); behavioral food refusal (two cases); and one case each of increased seizures, extreme drowsiness, constipation, vomiting, and diarrhea—common side effects of this type of diet.
“Clinically, more information is needed about the long-term effects of the ketogenic diet, including changes in blood lipid concentrations and persistent ketosis,” commented Dr. Wiznitzer, who was not affiliated with the study.
“Furthermore, better identification of epilepsies that benefit from starting early on the ketogenic diet and comparisons between the choices of ketogenic diet are needed.” Dr. Wiznitzer also called for “a better delineation of the mechanism of action of the diet and the development of a medication that would duplicate its effects.” (Lancet Neurol. 2008 May 3 [Epub doi:10.1016/S1474–4422(08)70093–0]).
The study was funded by the HSA Charitable Trust, Smiths Charity, Scientific Hospital Supplies, and the Milk Development Council.