The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial.
Level 2 - randomized trial
Open-label randomized controlled trial
PubMed 18456557 · doi:10.1016/S1474-4422(08)70092-9
What was done
A randomized controlled trial evaluated the efficacy of the ketogenic diet in 145 children aged 2 to 16 years with drug-resistant epilepsy (failing at least two antiepileptic drugs and experiencing daily seizures or more than seven per week). Participants were randomly assigned to initiate a ketogenic diet immediately (n=73) or after a 3-month delay as a control group (n=72), with no other treatment modifications. The study was open-label (unblinded to participants and investigators). The primary endpoint was seizure reduction at 3 months analyzed on an intention-to-treat basis; tolerability was assessed via questionnaire.
What was found
Data were available for 103 children at 3 months (54 diet, 49 control). Across the cohort, 16 children did not receive the intervention, 16 lacked adequate data, and 10 withdrew before 3 months (6 due to intolerance). At 3 months, mean percentage of baseline seizures was 62.0% in the diet group versus 136.9% in the control group (a 75% decrease, 95% CI 42.4–107.4%; p < 0.0001). Seizure reduction of greater than 50% occurred in 38% (28/73) of the diet group versus 6% (4/72) of controls (p < 0.0001). A greater than 90% reduction was observed in 7% (5/73) of the diet group versus 0% of controls (p = 0.0582). Efficacy did not differ between symptomatic generalized and focal epilepsy syndromes. Reported side effects at 3 months were constipation, vomiting, lack of energy, and hunger.
Why it matters
This trial provided randomized evidence demonstrating that the ketogenic diet substantially reduces seizure frequency in children with drug-resistant epilepsy.
Limits
The trial was open-label, introducing potential reporting bias from unblinded parents and investigators. There was substantial attrition, with 42 of 145 randomized children (29%) not contributing 3-month data. The randomized comparison period was limited to 3 months, leaving longer-term efficacy and safety unassessed in this trial phase.
Cited by
- supports A clinical trial led by Helen Cross demonstrated that ketogenic metabolic therapy significantly reduces epileptic seizures in children.