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Mechanism of Anticonvulsant Action Of Ketogenic Diet:  Studies in Animals With Experimental Seizures and in Children With Petit Mal Epilepsy

J. GORDON MILLICHAP, MD; JAMES D. JONES, MD; BERNARD P. RUDIS, MD
Am J Dis Child. 1964;107(6):593-604. doi:10.1001/archpedi.1964.02080060595008.
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Introduction  In 1921, Wilder 1 introduced a high-fat, low-carbohydrate diet for the treatment of epilepsy and later, Peterman,2 Helmholz,3 Keith,4 and Livingston5 established its effectiveness by clinical trial. A more recent report (Millichap, 1963)6 confirmed the efficacy of the diet, recommended its use as an anticonvulsant adjuvant in children with seizures resistant to other therapies or with hypersensitivity to drugs, and stressed the importance of detailed instruction of the parent by dietician and physician, and hospitalization of the patient for the proper introduction of the therapy.Despite its prolonged use and proven value, the exact mechanism of action of the ketogenic diet is unknown. Some authors have equated the beneficial effect with the degree of ketosis whereas others have stressed the importance of acidosis and diuresis 7-12 and the action has been compared to that of acetazolamide. The results of previous studies were sometimes contradictory

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