The ketogenic diet is indicated as an adjunctive (additional) treatment in children and young people with drug-resistant epilepsy. It is approved by national clinical guidelines in Scotland, England, and Wales and reimbursed by nearly all US insurance companies. Children with a focal lesion (a single point of brain abnormality causing the epilepsy) who would make suitable candidates for surgery are more likely to become seizure-free with surgery than with the ketogenic diet. About a third of epilepsy centres that offer the ketogenic diet also offer a dietary therapy to adults. Some clinicians consider the two less restrictive dietary variants—the low glycaemic index treatment and the modified Atkins diet—to be more appropriate for adolescents and adults. A liquid form of the ketogenic diet is particularly easy to prepare for, and well tolerated by, infants on formula and children who are tube-fed.
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On the ketogenic diet, carbohydrates are restricted and so cannot provide for all the metabolic needs of the body. Instead, fatty acids are used as the major source of fuel. These are used through fatty-acid oxidation in the cell's mitochondria (the energy-producing parts of the cell). Humans can convert some amino acids into glucose by a process called gluconeogenesis, but cannot do this by using fatty acids. Since amino acids are needed to make proteins, which are essential for growth and repair of body tissues, these cannot be used only to produce glucose. This could pose a problem for the brain, since it is normally fuelled solely by glucose, and most fatty acids do not cross the blood–brain barrier. However, the liver can use long-chain fatty acids to synthesise the three ketone bodies β-hydroxybutyrate, acetoacetate and acetone. These ketone bodies enter the brain and partially substitute for blood glucose as a source of energy.
The ketogenic diet reduces seizure frequency by more than 50% in half of the patients who try it and by more than 90% in a third of patients. Three-quarters of children who respond do so within two weeks, though experts recommend a trial of at least three months before assuming it has been ineffective. Children with refractory epilepsy are more likely to benefit from the ketogenic diet than from trying another anticonvulsant drug. Some evidence indicates that adolescents and adults may also benefit from the diet.