Ketogenic Diet Prevents, Controls Seizures in Children CME
News Author: Caroline Cassels
Disclosure: Caroline Cassels has disclosed no relevant financial relationships.
May 6, 2008 — The ketogenic diet is effective in preventing and controlling seizures in children with drug-resistant epilepsy. The first randomized controlled trial of this treatment shows the high-fat, carbohydrate restricted diet can cut seizure rates by more than 50% in this patient group.
"We have shown that the diet has efficacy and should be included in the management of children who have drug-resistant epilepsy. However, the diet is not without possible side effects, which should be considered alongside the risk benefit of other treatments when planning the management of such children," the authors write.
Led by Professor Helen Cross of the Institute of Child Health and Great Ormond Street Hospital for Children National Health Systems Trust in the United Kingdom, the study is published online in the May 3 issue of
Lancet Neurology.
Although the diet has been used since the 1920s to treat children with epilepsy and has been shown to be effective in both retrospective and prospective observational studies, the authors point out this is the first time it has been subjected to a randomized controlled trial.
"The aim of this study was to investigate whether there are clear benefits in terms of seizure control in children with epilepsy who were treated with the ketogenic diet for 3 months compared with a control group of children whose treatment did not change," they write.
The study included 145 children between the ages of 2 and 16 years who had at least daily seizures, had failed to respond to at least 2 antiepileptic drugs, and had not been previously treated with the diet.
All children had baseline seizure levels recorded during a 4-week period. Following this, 73 children were randomized to receive the ketogenic diet either immediately or after a 3-month delay. Both groups had no other changes to treatment.
Surprise Finding
The study's primary endpoint was a reduction in the number of seizures. In addition tolerability of the diet was assessed at 3 months. Complete data were available for 54 children in the diet group and 49 in the control group.
Using baseline figures as 100%, the investigators found that the number of seizures in the diet group dropped by 38%, whereas the control group experienced a 36.9% increase in seizures compared with baseline.
Twenty-eight of the 54 children who completed 3 months of following the diet had a greater than 50% seizure reduction compared with 4 of the 49 children in the control group. Five of the children in the diet group had a more than 90% reduction in seizure frequency compared with none in the control group.
The increase in seizure frequency in the control group, said the authors, was a "surprise" since there was no change in their treatment. The most likely explanation for this phenomenon was an unusual increase in seizure frequency in 3 of the children. The investigators note that when these data were excluded from the results the increase in seizure frequency in the control group during the 3-month period was only 12%.
The authors also found there was no difference in response to the diet among children with different types of seizures — those with seizures of generalized origin vs those with seizures of symptomatic focal origin.
Fewer than 25% of the 55 children following the diet for 3 months experienced adverse effects such as vomiting, lack of energy, or hunger. Slightly fewer reported diarrhea, abdominal pain, or taste problems. The most frequent single problem reported was constipation.
However, none of the children had adverse effects so severe that they withdrew from the study. In fact, in most cases adverse effects were effectively managed by adjusting the diet.
Careful Patient Selection Warranted
The authors note that the rate of nonstarters and withdrawers in the study was high, a finding which the authors indicate has inferences for patient selection for the ketogenic diet.
"This has important implications for the careful use of scarce dietetic resources because the initial ketogenic calculations and monitoring are time consuming. The initial assessment and screening process is vital and future inclusion criteria should ensure that children with pre-existing behavioral feeding problems are appropriately treated before they embark on a restricted diet," the authors note.
Long-term efficacy of the diet at 6 and 12 months will be reported in a future article comparing classical ketogenic diet, which is based on a ratio of fat:carbohydrate and protein of 3:1 or 4:1, vs a modified diet introduced in the 1970s that uses medium chain triglycerides (MCT) as an alternative fat source.
In an accompanying editorial, Max Wiznitzer, MD, a pediatric neurologist at Rainbow Babies and Children's Hospital in Cleveland, Ohio, calls for more research into the long-term effects of the ketogenic diet, including changes in blood fat concentrations and persistent ketosis.
Furthermore, he points out there is a need for better identification of epilepsies that benefit from starting the ketogenic diet early and comparisons between the choices of ketogenic diet.
Finally, writes Dr. Wiznitzer, "a better delineation of the mechanism of action of the diet and the development of a medication that would duplicate its effects are needed."
The study was supported by HSA, Smiths Charity, Scientific Hospitals Supplies, and the Milk Development Council. UCL Institute of Child Health received funding as a National Institute for Health & Research Specialist Biomedical Research Centre.
Dr. Cross has disclosed receiving educational grants and honoraria for educational talks from UCB, Janssen Cilag, Eisai, and SHS International.
Lancet Neurol. Published online May 3, 2008.
Clinical Context
The ketogenic diet is high in fat and low in carbohydrate as has been shown in observational studies and is efficacious in reducing seizure frequency in children with epilepsy resistant to multiple medications. However, there are no randomized trials examining its efficacy for different seizure types. There is a new version of the ketogenic diet with replacement of long-chain triglycerides by MCTs, which is believed to be more ketogenic than the classical diet.
This study is an open randomized controlled trial of children conducted at 2 pediatric neurologic referral centers to compare the effect of a classical or MCT ketogenic diet vs a controlled (usual) diet on frequency of seizures in children with drug-resistant epilepsy.
Study Highlights
- Included were children, referred to 2 pediatric neurologic centers, between ages 2 and 16 years who had seizures daily or at least 7 times a week and who had not responded to 2 antiepileptic drugs and had not been following a ketogenic diet.
- Excluded were children with hyperlipidemia, history of renal stones, or organic-acid deficiency syndromes.
- During a baseline 4-week period, children had seizure frequency recorded by diary by their parents.
- 145 children were randomized, of whom 54 in the ketogenic diet group and 49 in the controlled diet group were analyzed by intent-to-treat.
- After 3 months, children in the controlled group were also given the ketogenic diet.
- Primary outcome was seizure frequency recorded by parents for 6 categories of seizures.
- No changes were made during the study in the child’s antiepileptic medications.
- Children were reviewed as outpatients at 6 weeks and 3 months and monitored by telephone between visits.
- The ketogenic diet group received either the classical or the MCT diet.
- The classical diet was calculated in a 2:1 ratio for fat to protein and carbohydrate and increased to 3:1 then 4:1 ratio for 1 to 2 weeks as tolerated.
- MCT diets were started at full prescription for carbohydrate (15%), protein (10%), and long-chain fat (30%). MCT content was increased for 7 to 10 days to a level of 45% of energy.
- The ketogenic diet was adjusted as tolerated by the dietician and to manage seizure frequency.
- Ketosis was assessed by twice-daily home testing with Ketostix (Bayer, Leverkusen, Germany).
- Children following the control diet received a usual diet with no dietetic input.
- 78 children had generalized epilepsy, and 57 had focal epilepsy.
- A little more than 50% were boys.
- At baseline, 6 were not taking any medications, 20 were taking 1 medication, 53 were taking 2 medications, and 54 were taking 3 medications.
- Mean seizure frequency was reduced by 38% in the ketogenic diet group and increased by 37% in the control group.
- The difference between the mean percentage of baseline seizures at 3 months for the 2 groups was 74.9% (P < .0001).
- At 3 months, freedom from seizures was attained for 1 child in the diet group and none in the control group.
- 7% in the ketogenic diet group vs 0% in the control group had a greater than 90% reduction in daily seizure frequency.
- 38% in the ketogenic group vs 6% in the control group had a greater than 50% reduction in daily seizure frequency.
- The improvement in frequency of daily seizures was seen with both generalized and focal seizures.
- The main adverse effects linked with the ketogenic diet were constipation for 33% (24% required medication for constipation), vomiting for 24%, lack of energy for 24%, and hunger for 22%.
- The authors concluded that responder rates for children following the ketogenic diet were similar to those seen in randomized controlled trials of newer antiepileptic drugs against placebo and that the diet should be included in the treatment of children with drug-resistant epilepsy.
- They noted that response rates for the ketogenic diet were lower than previously reported for ketogenic diets in observational studies.
Pearls for Practice
- Use of the ketogenic diet in children with drug-resistant epilepsy is associated with significantly reduced daily seizure frequency.
- The ketogenic diet is efficacious for both generalized and focal seizures, and main adverse effects include constipation, vomiting, lack of energy, and hunger.
Anyway, chocolate is good for you. 
