NEW ORLEANS — A gradual induction of the ketogenic diet that spares children the need to fast is just as effective in seizure reduction as the traditional protocol, Christina Bergqvist, M.D., said at the annual meeting of the American Epilepsy Society.
The gradual induction protocol is also easier on children and their families, and is associated with fewer adverse events. Many families are put off by the idea of 24-48 hours of fasting, said Dr. Bergqvist of the Children's Hospital of Philadelphia.
“The management of this diet has changed very little since it was invented about 84 years ago,” she said in an interview. “For some families, who are already dealing with intractable seizures, the idea of putting their child through the fasting and the adverse events that go along with it is enough for them to decide against it.”
Dr. Bergqvist randomized 48 children with intractable seizures to either the standard fasting or gradual induction approach. The children were aged 1-14 years (median age 5 years). They had not responded to a median of eight antiepileptic drugs. Half of the group had generalized seizures, and half had partial seizures.
Each group began the study with a day of regular meals. The standard induction group then had a 24-hour fast, followed by 4 days of full ketogenic diet meals (90% fat) of increasing calorie amounts (33% of normal daily calories on day 1, 67% on day 2, and then 100% of daily calorie intake).
The gradual induction group had a day of regular meals followed by 4 days of gradually increased fat intake: 50% of calories from fat, 69% from at, 82% from fat, and, finally, standard ketogenic meals of 90% calories from fat.
Ketosis was measured by whole blood levels of β-hydroxybutyrate (BHB). BHB levels increased more rapidly and to a higher degree in the standard induction group, from about 1 μmol/L on day 1 to 4.5 μmol/L on day 3. Thereafter, BHB remained around 5 μmol/L. The BHB level rose more slowly in the gradual induction group, not reaching 4 μmol/L until day 5 and reaching 5 μmol/L by day 6.
Dr. Bergqvist said she considers BHB a more accurate measurement of ketosis than urinary acetoacetate, the level of which can be affected by dehydration. Additionally, she said, BHB is thought to have a significant impact on seizure reduction. Animal studies have shown that BHB potentiates the production of the neurotransmitter γ-aminobutyric acid. At 3 months' follow-up, during which the children maintained the full ketogenic diet, there was no significant difference in seizure reduction between the two groups. In the standard induction group, 58% of patients had a seizure reduction of greater than 50%, and 21% were seizure free. In the gradual induction group, 67% of patients had a seizure reduction of greater than 50% at 3 months, and 21% were seizure free.
Dr. Bergqvist is still evaluating the adverse events but did say that hypoglycemia, nausea, vomiting, diarrhea, and lethargy were less frequent and less severe with gradual induction.
“Because these side effects can be pretty significant for some children, everybody has to start the diet as an inpatient, and usually only large university medical centers can offer it,” she said. “But based on the results of this study, it's possible that we could adjust the protocol, and if the side effects were less severe, maybe the diet could be more widely offered.”