Seizures that are resistant to standard medications remain a major clinical problem. One underutilized option for patients with medication-resistant seizures is the high-fat, low-carbohydrate ketogenic diet. The diet received its name based on the observation that patients consuming this diet produce ketone bodies (e.g., acetoacetate, β-hydroxybutyrate, and acetone). Although the exact mechanisms of the diet are unknown, ketone bodies have been hypothesized to contribute to the anticonvulsant and antiepileptic effects. In this review, anticonvulsant properties of ketone bodies and the ketogenic diet are discussed (including GABAergic and glutamatergic effects). Because of the importance of ketone body metabolism in the early stages of life, the effects of ketone bodies on developing neurons in vitro also are discussed. Understanding how ketone bodies exert their effects will help optimize their use in treating epilepsy and other neurological disorders.

OBJECTIVE Kidney stones are an adverse event with the ketogenic diet (KD), occurring in approximately 6% of children who are started on this therapy for intractable epilepsy. Potassium citrate (Polycitra K®) is a daily oral supplement that alkalinizes the urine and solubilizes urine calcium, theoretically reducing the risk of kidney stones. METHODS Children at Johns Hopkins Hospital starting the KD from 2000–2008, with at least 1 month of follow-up, were evaluated (n=313). From 2000–2005, children were treated with daily Polycitra K® at 2 meq/kg/day only in the setting of identified hypercalciuria; whereas since 2006 it has been started in all children empirically at KD onset. RESULTS Polycitra K® was administered to 198 children preventatively overall, of whom 4 (2.0%) developed kidney stones, compared to 11 of 105 (10.5%) who did not receive Polycitra K®, P= .003. Two children since 2006 refused Polycitra K®, one of whom developed a kidney stone. Successful empiric administration of Polycitra K® at KD onset resulted in a kidney stone incidence of 0.9% (1 of 106) compared to administration only due to hypercalciuria, 6.7% (13 of 195), P =.02. Polycitra K® resulted in less acidic urine (mean pH 6.8 vs. 6.2, P = .002), but not reduced serum acidosis. No side effects of oral citrates were reported. CONCLUSIONS Oral potassium citrate is an effective preventative supplement against kidney stones in children receiving the KD, achieving its goal of urine alkalinization. Universal supplementation is warranted.

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