The ketogenic diet is a high-fat and low-carbohydrate diet which was introduced into epilepsy therapy in the 1920s, and which in recent times has been the subject of a resurgence of interest. Its use is confined to the treatment of severe childhood epilepsy that has proved resistant to more conventional therapy. It has no role in adult epilepsy, where its use has proved difficult and dangerous.
The diet is high in fat and low in carbohydrate, with adequate protein, and provides nutrition with 1 g/kg of protein and 5-10 g of carbohydrate per day, the remainder of the calories (usually 75% of the recommended daily allowance) being in the form of long-chain triglycerides.
The diet must be followed strictly, an arduous and difficult task for the child and parent(s) alike.
Exactly how the diet exerts its undoubted antiepileptic effect is unknown. It mimics the biochemical changes of starvation (low carbohydrate intake) and this results in a switch from aerobic to ketogenic metabolism and the production of ketone bodies in the liver. These are transported into the brain by a monocarboxylic acid transporter, where they are utilized instead of glucose for energy production. This metabolic change has marked antiepileptic effects, as demonstrated in animal and human studies. To alter metabolism, however, requires dedication to a diet that is difficult to maintain and often unpalatable.
The diet is usually reserved for children with West syndrome, Lennox-Gastaut syndrome or other less-specific forms of severe epilepsy. Patients with gastrostomy tubes in place may be ideal candidates. A special indication is in children with glucose transporter protein (GLUT-1) deficiency and pyruvate dehydrogenase deficiency, where the diet is first-line therapy and can be life-saving. The diet is potentially dangerous, and should be avoided, in pyruvate car-boxylase deficiency, porphyria, carnitine deficiency, fatty acid oxidation defects and in mitochondrial disorders.
The exact constitution of the diet must be calculated individually for each patient. The ratio of fats to carbohydrates and protein is based on the age, size, weight and activity level of the patient. A young child or infant is often prescribed a 3 : 1 diet to provide additional protein and older children a 4 : 1 diet. Obese children and adolescents are usually given a 3:1 diet. Calorie intake is generally about 75% of the recommended daily intake for age. Fluid intake must be rigorously maintained, and supplementation with magnesium, zinc, vitamin D, vitamin C, vitamin B complex and calcium is recommended.
The effects on epilepsy can be dramatic. Early studies in the 1920s and 1930s consistently showed impressive results, and these have been largely confirmed in more recent investigations carried out to modern standards. A recent study from Johns Hopkins University showed, at 1 year, a reduction in seizures of more than 50% in 50% of 150 treated children, and a reduction of more than 90% in 27%. At 3 -6 years, 44% maintained the improvement. The use of the diet allows a reduction of adjunctive drug therapy, which is an added benefit. Other benefits of the diet include improvement in behaviour in those with and without autism. The diet can be given for months or years. A typical period of treatment is 1-2 years, if the diet proves initially successful. About 10% of children maintain the diet for 4 or more years, and one patient is reported who has maintained the diet for 15 years with no major side-effects. Discontinuation of the diet should take place gradually over 3-6 months.
Side-effects are not uncommon. Vomiting, dehydration and food refusal are common initially but are transitory.
Other minor side-effects include constipation, oesophageal reflux and acidosis. The effect of the diet on growth is a problem. A recent review of the diet in 237 children showed that the rate of weight gain decreased at 3 months but then remained constant for up to 3 years. There is also an effect on height. Renal stones occur in 5-8% of patients. Hypercholesterolemia is common. Rare side-effects that have been reported include cardiomyopathy, pancreatitis, bruising, vitamin deficiency, hypoproteinaemia, Fanconi's renal tubular acidosis and prolonged QT interval. In adults, for whom the diet is not normally recommended, coronary heart disease and myocardial infarction have occurred, associated with hypercholesterolaemia.
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