Is Long-term Use of the Ketogenic Diet Safe and Effective?
Abstract and Commentary
By John J. Caronna, MD, Vice-Chairman, Department of Neurology, Cornell University Medical Center, Professor of Clinical Neurology, New York-Presbyterian Hospital. Dr. Caronna reports no financial relationship relevant to this field of study.
Synopsis: Patients treated with the ketogenic diet for more than 6 years showed sustained seizure reduction (90% decrease in seizure frequency) with few serious side effects.
Source: Groesbeck DK, et al. Long-term use of the ketogenic diet in the treatment of epilepsy. Developmental Medicine & Child Neurology. 2006;48:978-981.
The purpose of this study was to evaluate the safety and efficacy of the ketogenic diet in the small fraction of patients who remain on the diet longer than the usual length of treatment (2-3 years). Patient records were retrospectively reviewed to identify patients who were started on the ketogenic diet between July 1993 and May 1999, and who remained on the diet for a continuous period of at least 6 years. Out of 386 patients who were started on the ketogenic diet, 28 patients were identified and were ages 7-23 years. The median time on the ketogenic diet was 7 years 9 months (range 6-12 years), median age at first seizure was 6 months, median age at diet onset was 3 years 9 months, median number of medications tried before diet onset was 5, and median seizure frequency per week at the start of the diet was 630 (range 1-1400). Of the 28 long-term patients, 24 experienced more than a 90% decrease in seizure frequency but only 3 achieved total seizure freedom. At diet onset, patients were on a median of 2 anticonvulsant medications (range 1-4) and at the most recent follow up or upon diet completion, the patients were on a median of one medication (range = 0-4); 9 patients were medication free.
At the time of records review, 19 patients were still on the diet. Compliance with the intricacies of the diet improved over time; however, many patients were fed by gastrostomy, which would eliminate some of the difficult aspects of the ketogenic diet, such as palatability and portion control. The diet was maintained on a long-term basis for these 28 patients because of sustained and dramatic seizure control, as well as concern by the families that changing to an antiepileptic medication would have more cognitive side effects than the diet. Many families resisted termination of the diet, even when the physician suggested doing so. Nine patients stopped the diet because of poor growth (2), seizure freedom (2), lack of benefit (2), restrictiveness (1), and death (1).
The authors investigated the various factors that might affect seizure control and side effects and noted the following: 1) Severe vs mild ketosis did not affect seizure control (p = 0.298); 2) The diet had an adverse effect on long-term growth, both weight and height (p = 0.011); 3) There was an increased risk of developing kidney stones; 4) Fractures occurred frequently; 5) Dyslipidemia was an uncommon side effect and overall lipid profiles were within the normal range; 6) Liver function tests were unaffected; 7) Constipation was reported as a side effect of the diet in 15 patients; 8) The diet did not contribute to the death of the single patient who died while on the diet.
This retrospective chart review from Johns Hopkins reinforces our belief in the efficacy and safety of the ketogenic diet for patients with intractable seizures. The use of the ketogenic diet resulted in > 90% reduction of seizure frequency in 30-35% of children with intractable epilepsy. The long-term safety data presented here would suggest that for ketogenic diet responders, using the diet for more than 2-3 years is safe. More than half of the parents cited a side-effect profile for the ketogenic diet that was superior to medication, and this was their primary reason for staying on the diet. Most patients were on fewer medications after starting the diet and nearly a third were on no anticonvulsant medication at all.
However, continuous safety monitoring is imperative during the long-term use of the ketogenic diet. Physicians should monitor growth parameters closely. Due to the risk of developing kidney stones, prophylactic oral alkalinization, frequent monitoring for hematuria, and liberal fluid intake have been recommended for patients who are on the diet for prolonged periods of time. The high risk of fractures associated with the diet calls for vigilant monitoring of bone density and the administration of calcium and vitamin D supplements.
Because of the retrospective, self-report design of this study, confounding variables could be significant, such as the effects of cerebral palsy, developmental delays, anticonvulsant medications, and motor deficits that could independently contribute to growth delay, independent of the diet. The observed high rate of bone fractures and kidney stones may represent a selection bias as opposed to a true increase in incidence of these adverse effects.