Ketogenic diet offers alternative to drugs for epilepsy

Studies have focused on efficacy and safety of the ketogenic diet, which may be used instead of drug therapy for refractory epilepsy in some children.
By John Russo Jr./

VICUS.COM (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 ketogenic diet

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.

Epilepsy in the United States

Epilepsy 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.In 1995, 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 success.Approximately 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.

Source: The Epilepsy Foundation;

By 1938, when diphenylhydantoin (later called phenytoin) became available, attention turned from diet to pharmacologic options as the primary treatment for epilepsy. Lack of use led to the erroneous perception that the diet lacked efficacy.

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, 1996).

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 options available.”

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 al., 1998), 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, 1996).

Potential medical complications

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 al., 1999).

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 al., 1998).


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.

John Russo Jr., PharmD, is senior vice president of medical communications at He is a pharmacist and medical writer with more than 20 years of experience in medical education.

Arnold ST, Dodson WE. Epilepsy in children. Baillieres Clin Neurol. 1996 Dec; 5(4):783-802.Ballaban-Gil K, Callahan C, O’Dell C, et al. Complications of the ketogenic diet. Epilepsia. 1998 Jul; 39(7):744-8.Ben-Menachem E. New antiepileptic drugs and non-pharmacological treatments. Curr Opin Neurol. 2000 Apr; 13(2):165-70.Casey JC, McGrogan J, et al. The implementation and maintenance of the Ketogenic Diet in children. J Neurosci Nurs. 1999 Oct; 31(5):294-302.Katyal NG, Koehler AN, et al. The ketogenic diet in refractory epilepsy: the experience of Children’s Hospital of Pittsburgh. Clin Pediatr (Phila). 2000 Mar; 39(3):153-9.

Panico LR, Demartini MG, et al. The ketogenic diet in infantile refractory epilepsy: electroclinical response, complications and secondary effects. [Article in Spanish]. Rev Neurol. 2000 Aug 1-15; 31(3):212-20.

The Epilepsy Foundation:

Trevathan E. Special meeting: Controversies in epilepsy. The ketogenic diet. Epilepsy Update. Issue #6 1996:

Vining EP. Clinical efficacy of the ketogenic diet. Epilepsy Res. 1999 Dec; 37(3):181-90.

Vining EP, Freeman JM, Ballaban-Gil K, et al. A multicenter study of the efficacy of the ketogenic diet. Arch Neurol. 1998 Nov; 5(11):1433-7.