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Ketogenic Diet Cuts Kids' Epileptic Seizures Source: www.Medpagetoday.com By Judith Groch Date: 10/1/08
Seizures in children with drug-resistant epilepsy were reduced by the ketogenic diet, which stresses high fat, low carbohydrates, and controlled protein, the first randomized trial of the regimen found.
Action Points
*
Explain to interested patients that the high-fat, low-carbohydrate diet
to cut epileptic seizures in drug-resistant children was highly
effective but produced side effects such as constipation and vomiting.
*
Explain that more information is needed about the long-term effects of
this high-fat diet, including changes in blood lipid concentrations and
persistent ketosis.
In
the first randomized trial of the diet, the number of seizures over
three months declined by an average of about a third compared with a
rise of about a third in a control group, Elizabeth G. Neal, Ph.D., of
University College London, and colleagues reported online and in the
June issue of Lancet Neurology.
Although
the ketogenic diet has been widely used to treat children with
drug-resistant epilepsy since the 1920s and was found beneficial in
observational studies, a Cochrane review had found no randomized
controlled trials in the literature.
Although
the exact mechanisms of action are unclear, the high fat and restricted
carbohydrate content of the diet is thought to mimic the biochemical
response to starvation, when ketone bodies, rather than sugars, become
the main fuel for the brain's energy.
The
study included 145 children, ages two to 16, who had daily seizures (or
more than seven a week), had failed to respond to at least two
antiepileptic drugs, and had not been treated previously with a
ketogenic diet. Enrollment ran from December 2001 through July 2006.
Children
were seen at one of two hospital centers or a residential center for
young people with epilepsy. Children were randomly assigned to a
ketogenic diet, either immediately or after a three-month delay
(control group), with no other changes in treatment for either group.
All children were given vitamin and mineral supplements.
After the trial, the controls were crossed over to the ketogenic diet.
The
ketogenic diet came in two forms. Classical diets (37 children) were
started at a 2:1 fat:protein and carbohydrate ratio and gradually
increased to a 3:1 or 4:1 ratio.
The
medium-chain triglycerides ketogenic diet (39 children) was started
with carbohydrate generally 15% of total energy, protein usually 10%
and long-chain fat usually 30% of total energy. The medium-chain
triglycerides fat content was increased over seven to 10 days, as
tolerated, usually to 45% of total energy.
Early
withdrawals were recorded, and seizure frequency on the diet was
assessed after three months and compared with that of the controls.
Tolerability of the diet was assessed by questionnaire at three months.
Seventy-three
children were assigned to the ketogenic diets and 72 to the control
group. Data from 103 children were available for analysis including 54
following ketogenic diets and 49 controls.
After
three months, the mean percentage of baseline seizures was
significantly lower in the diet group than among the controls (62%
versus 136.9%, for a 75% decrease, 95% CI 42.4 to 107.4%, P0.0001).
Of
the children in the diet group, 28 (38%) of children who completed the
three-month diet had more than a 50% seizure reduction compared with
just four (6%) controls (P0.0001).
Five
children (7%) in the diet group had a greater than 90% seizure
reduction compared with none in the control group (P=0.0582).
There
was no significant difference in the efficacy of the treatment between
symptomatic generalized or symptomatic focal syndromes.
The most frequent side-effects reported at the three-month review were constipation, vomiting, lack of energy, and hunger.
Discussing
limitations, the authors noted that the study would have been improved
by the inclusion of prospective seizure data from the children who
either did not start treatment or who withdrew before three months.
The
study would also have been improved by double-blind randomization,
although that would have been impossible given the need for parents,
care-givers, and children to cooperate.
The
results from this controlled trial of the ketogenic diet support its
use in children with treatment-intractable 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 these children, the researchers advised.
In
an accompanying comment, Max Wiznitzer, M.D., of Rainbow and Children's
Hospital in Cleveland, wrote that the study provides further support
for the usefulness of this type of controlled study.
Clinically,
he said, more information is needed about the long-term effects of the
diet, including changes in blood lipid concentrations and persistent
ketosis.
Also
needed are better identification of epilepsies that benefit from
starting early on the diet as well as comparisons among choices of the
ketogenic diet.
Functionally,
a better understanding of the mechanisms of action and the development
of a medication that would duplicate the diet's effects are also
needed, Dr. Wiznitzer wrote.
Funding
for the study came from HSA, Smiths Charity, Scientific Hospital
Supplies, and the Milk Development Council. University College London
Institute of Child Health received funding as a National Institute for
Health & Research Specialist Biomedical Research Center.
Co-author
J. Helen Cross, Ph.D, has received educational grants and honoraria for
educational talks from UCB, Janssen Cilag, Eisai, and SHS International.
Drs. Neal and Wiznitzer declared no conflicts of interest.
Primary source: The Lancet Neurology Source reference: Neal
EG, et al "The ketogenic diet for the treatment of childhood epilepsy:
A randomized controlled trial" The Lancet Neurology 2008: DOI:
10.1016/S1474-4422(08)70092-9.
Copyright 2007. All Rights Reserved. |
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