A high-fat diet, known as the ketogenic diet, reduces seizures in children with drug-resistant epilepsy, a new study shows.

In the trial, the 54 children who followed the ketogenic diet for three months had their overall seizure rates fall by about 30 per cent. Twenty-eight of the children had their seizure rates cut in half, while five children had a 90 per cent reduction in seizure rates.

In comparison, seizures among the control group, which was not given the ketogenic diet, actually rose by more than 30 per cent.

The study, conducted by a team from the Institute of Child Health and Great Ormond Street Hospital in London, was published online and in the June edition of the journal The Lancet Neurology.

Experts estimate that anticonvulsant medication does not work for about 20 per cent of epilepsy patients. Since the 1920s, the ketogenic diet has been a common treatment to control seizures in children who don't respond to medication.

However, while observational studies have proven the efficacy of the diet, this is the first clinical trial to prove that it does work.

It is not clear how it affects epilepsy, but scientists hypothesize that the high-fat, low-carbohydrate nature of the diet mimics the body's response to starvation, when ketone bodies, rather than sugars, become the body's main fuel source.

Ketone bodies are by-products of fatty acids, and are used by the heart and brain as a source of energy, the brain particularly so during a period of fasting.

In a reflection accompanying the study, Dr. Max Wiznitzer of the Rainbow Babies and Children's Hospital in Cleveland said that while the exact effect that ketone bodies have in the brain is not known, it could be that they act as an anticonvulsant, or they simply stabilize brain activity by increasing its energy stores.

However, once scientists know for sure, the next step will be to develop a medication that mimics this effect.

The downside of the diet is that it can lead to a variety of side effects such as constipation, vomiting, lack of energy and hunger. The long-term effects are also unknown, and the researchers cautioned that this form of treatment should only be tried under a doctor's supervision.

"We have shown that the diet has efficacy and should be included in the management of children who have drug-resistant epilepsy," the authors wrote.

"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."

Abstract:

The ketogenic diet for the treatment of childhood epilepsy: a randomized controlled trial

Elizabeth G. Neal, Hannah Chaffe, Ruby H. Schwartz, Margaret S. Lawson, Nicole Edwards, Geogianna Fitzsimmons, Andrea Whitney, J. Helen Cross

Background: The ketogenic diet has been widely and successfully used to treat children with drug-resistant epilepsy since the 1920s. The aim of this study was to test the efficacy of the ketogenic diet in a randomised controlled trial.

Methods: 145 children aged between 2 and 16 years who had at least daily seizures (or more than seven seizures per week), had failed to respond to at least two antiepileptic drugs, and had not been treated previously with the ketogenic diet participated in a randomised controlled trial of its efficacy to control seizures. Enrolment for the trial ran between December, 2001, and July, 2006. Children were seen at one of two hospital centres or a residential centre for young people with epilepsy. Children were randomly assigned to receive a ketogenic diet, either immediately or after a 3-month delay, with no other changes to treatment (control group). Neither the family nor investigators were blinded to the group assignment. Early withdrawals were recorded, and seizure frequency on the diet was assessed after 3 months and compared with that of the controls. The primary endpoint was a reduction in seizures; analysis was intention to treat. Tolerability of the diet was assessed by questionnaire at 3 months. The trial is registered with ClinicalTrials.gov, number NCT00564915.

Findings: 73 children were assigned to the ketogenic diet and 72 children to the control group. Data from 103 children were available for analysis: 54 on the ketogenic diet and 49 controls. Of those who did not complete the trial, 16 children did not receive their intervention, 16 did not provide adequate data, and ten withdrew from the treatment before the 3-month review, six because of intolerance. After 3 months, the mean percentage of baseline seizures was significantly lower in the diet group than in the controls (62-0% vs 136-9%, 75% decrease, 95% CI 42.4-107.4%; p<0-0001). 28 children (38%) in the diet group had greater than 50% seizure reduction compared with four (6%) controls (p<0-0001), and five children (7%) in the diet group had greater than 90% seizure reduction compared with no controls (p=0-0582). There was no significant difference in the efficacy of the treatment between symptomatic generalised or symptomatic focal syndromes. The most frequent side-effects reported at 3-month review were constipation, vomiting, lack of energy, and hunger.

Interpretation: The results from this trial of the ketogenic diet support its use in children with treatment-intractable epilepsy.