(29 Nov. 2000) -- The ketogenic diet is an individually calculated and
rigidly controlled, high-fat, low- (or adequate) protein and
low-carbohydrate diet that is used to treat difficult-to-control
(refractory) epileptic seizures, primarily in children.
It was developed in the 1920s and is designed to mimic the
biochemical changes associated with fasting, which seems to have a
positive effect on seizure control (Vining, 1999). For patients or
health-care professionals who are considering its use as an
alternative to pharmacologic therapy for epilepsy, here is a review of
the comparative efficacy and safety of this therapeutic option.
Efficacy of the
In the 1920s, when few anticonvulsant drugs were available, it was
observed that ketosis (the
presence of excess ketones in the body; ketones are a byproduct of fat
metabolism) had a beneficial effect on seizure activity. The ketogenic
diet was an outgrowth of that observation.
and seizures affect 2.3 million Americans of all ages,
at an estimated annual cost of $12.5 billion in direct
and indirect costs. Approximately 181,000 new cases of
seizures and epilepsy occur each year; 10% of the
American population will experience a seizure in their
lifetimes; 3% will develop epilepsy by age 75.
300,000 children 14 and younger had epilepsy; 1.4
million adults younger than 64 and 550,000 adults 65
and older had epilepsy. Advances in medical treatment
enable many people to live normal lives free of
seizures and to achieve personal and professional
60% achieve remission after the first year; 15%
achieve control at a later date, but in 25%, seizures
resist control and become intractable. For this group
-- comprising hundreds of thousands of people, many of
them children -- epilepsy remains a formidable barrier
to normal life, affecting educational attainment,
employment and personal fulfillment.
By 1938, when
diphenylhydantoin (later called phenytoin) became available, attention
turned from diet to pharmacologic options as theprimary treatment for
epilepsy. Lack of use led to the erroneous perception that the diet
According to Edwin
Trevathan, M.D., MPH (master of public health), director of the
Comprehensive Epilepsy Program at the University of Kentucky, evidence
in support of the ketogenic diet for epilepsy has generally been based
on small, retrospective studies and anecdotal reports (Trevathan,
Researchers who published
on the ketogenic diet during the 1960s and 1970s generally reported
good results. For example, among 1,000 patients (792 with intractable
disease), seizures were controlled in 54% and marked improvement was
seen in 26%. Nevertheless, Trevathan emphasized, "It is difficult
to interpret these results in a modern context when talking about a
different patient population with different additional treatment
More recent studies
report less optimistic results. However, this may be due to the way in
which the results are reported. For example, Eileen Vining, M.D., and
colleagues in The Ketogenic Diet Multi-Center Study Group at The Johns
Hopkins Medical Institutions in Baltimore, Md. (Vining, et
reported that only 24 (47%) of 51 children with intractable epilepsy
remained on the diet for 12 months. Among those remaining, 11 (22% of
the initial population) had greater than a 90% decrease in seizures
(five were seizure-free), while nine (18% of the initial population)
had a 50% to 90% decrease in seizures.
If only the 24 children
who completed a full year of the diet are included in the analysis,
the response to therapy reported by Vining is similar to the older
study described by Trevathan. Approximately half of the children who
are able to stick with the ketogenic diet can expect to achieve
greater than 90% decrease in seizures and the rest can expect a 50% to
90% decrease in seizure activity, according to Vining.
Susan T. Arnold, M.D.,
and her team at the Washington University School of Medicine reviewed
what happened to 47 children and adults with various types of epilepsy
who were placed on the diet since 1991. Ages of the subjects ranged
from seven months to 28 years.
Before going on the diet,
they were averaging 28 seizures a week. The research team reported
that 34% of the 47 individuals reduced their seizures by more than
90%; 9% had between 50% and 90% fewer seizures, and 57% had less than
a 50% reduction. And 13% became seizure-free.
The researchers concluded
that the diet was well-tolerated and benefited a significant number of
patients. They also reported that patients with localization-related
epilepsy (seizures arising from an identified area of the brain) were
less likely than others to be helped by the diet, and that children
with Landau-Kleffner syndrome, a condition associated with continuing
electrical discharge during sleep, did not respond (Arnold and Dodson,
During the initial
hospitalization phase of treatment, hypoglycemia, vomiting,
dehydration and medication toxicity are possible. Once the child is
discharged, Jane Cassilly Casey, R.N., director of the Pediatric
Epilepsy Center at Johns Hopkins in Baltimore, Md., advises her
patients to be aware of potential complications (Casey, et
She said that
"caring for a sick child on the ketogenic diet can be a
challenge. Dehydration, constipation and severe acidosis are common
problems during childhood illnesses. Children on the diet are
susceptible to these complications because they are maintained on a
constant fluid restriction and a mild state of acidosis."
Acidosis is an abnormal increase in the acidity of body fluids.
Other less common but
potentially serious adverse events reported within the first month of
treatment include hypoproteinemia, abnormally high levels of lipids in
the bloodstream, hemolytic anemia and renal tubular acidosis caused by
Fanconi's syndrome. Elevations in liver function tests also have been
reported during the first year of treatment (Ballaban-Gil, et
The ketogenic diet is
primarily used under medical supervision to treat children for a
limited period of time, after which the diet may be slowly tapered and
regular food slowly re-introduced, according to the Epilepsy
Foundation. If seizures return, the diet may be re-instituted.
Studies are under way to
see if the ketogenic diet would work for some adults as well. Early
results suggest that it may, but the long-term effects of such a
high-fat diet are unknown.
Russo Jr., PharmD, is senior vice president of medical
communications at Vicus.com. He is a pharmacist and medical writer
with more than 20 years of experience in medical education.