ST. LOUIS—Ketogenic diets for seizure control do not require the traditional period of fasting to be effective and are much safer without it, researchers reported at the 29th National Meeting of the Child Neurology Society. Beth A. Zupec-Kania, RD, CD, and colleagues at Children’s Hospital of Wisconsin in Milwaukee said that their nonfasting protocol for rapid initiation of the diet “has allowed a smooth transition to the ketogenic diet while minimizing complications and inpatient hospital days.”

RAPID INITIATION AVOIDS COMPLICATIONS, SHORTENS HOSPITAL STAYS

“Our main findings were that the initial period of fasting is not necessary for the diet to be effective and that by day three of our protocol all of the patients had achieved high levels of urine ketones,” coauthor Edward H. Kovnar, MD, told Neurology Reviews in an interview. Dr. Kovnar is Associate Professor of Neurology and Pediatrics at the Medical College of Wisconsin in Milwaukee.

According to Ms. Zupec-Kania, the classic ketogenic diet involves an initial period of starvation that is followed by a diet consisting of a 3:1 to 4:1 ratio of fat to carbohydrate and protein. “During the fasting period, children may become hypoglycemic and hyperketotic, leading to nausea, vomiting, and irritability,” she said.

“There is a risk to fasting, especially for children with marginal nutritional status,” Dr. Kovnar said. “Fasting can lead to hypoglycemia and dehydration. As the child becomes ketotic, nausea and vomiting may interfere with tolerance of the diet,” he added. “The fasting period is not benign. There have been fatalities during this period. By avoiding an initial fast we were able to minimize complications and reduce hospital stays in our patients.” On most ketogenic diet protocols, patients are hospitalized for a week or more to monitor glucose levels and nutritional intake and output. The rapid initiation protocol reduced hospitalization to an average of three to four days.

The study included 11 patients age 12 months to 20 years. All had intractable seizures that had not been controlled by at least two conventional antiepileptic drugs. All patients were free of recognized inborn errors of metabolism and none were candidates for epilepsy surgery.

Children in this study were allowed to eat their usual breakfast at home, then they were admitted to the hospital and fed ketogenic meals totaling one third of the daily caloric diet goal. On the second day of admission the children were fed two thirds of the total daily caloric goal, and full calories were provided on the third day. Ketone levels were indicated as negative, trace, small, moderate, or large by urinalysis reagent strips.

Ms. Zupec-Kania reported that by the third day, all of the children had registered large urine ketones on two or more readings. “Improvement in seizure control was often seen within one week of starting the diet,” Dr. Kovnar added.

HOW IT WORKS—A CONTINUALLY EVOLVING MYSTERY

R. M. Wilder, MD, who developed the modern ketogenic diet, thought that the ketosis and acidosis resulting from minimal caloric intake produced an anticonvulsant effect. As noted by James Wheless, MD, fasting to control seizures has been recognized for centuries and may have been used in biblical times. “The ketogenic diet mimics the metabolic changes associated with the fasting state. Early investigators thought that a period of fasting was needed to turn on ketone production. Our data show that is not the case,” Dr. Kovnar said.

The mechanism responsible for the antiseizure effect of the ketogenic diet is unknown. In 1997, Swink et al suggested that the ketogenic diet causes a fundamental change in the brain’s metabolism from that of a glucose-based energy substrate to a ketone-based substrate and that this in some way increases the seizure threshold. They also pointed out that the change in seizure threshold occurs without affecting normal cognitive function. Although urine ketone levels are more readily monitored, Gilbert et al have recently noted that seizure control correlates better with serum ß-hydroxybutyrate.

“Our trial worked well because of the excellent collaboration between our clinical nutritionists, nursing staff, social worker, and medical staff. Anyone contemplating rapid initiation of the ketogenic diet should do so only with the help of a multidisciplinary team that specializes in the management of the ketogenic diet,” Dr. Kovnar said.

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