A Cochrane systematic review in 2018 found and analysed eleven randomized controlled trials of ketogenic diet in people with epilepsy for whom drugs failed to control their seizures. Six of the trials compared a group assigned to a ketogenic diet with a group not assigned to one. The other trials compared types of diets or ways of introducing them to make them more tolerable. In the largest trial of the ketogenic diet with a non-diet control, nearly 38% of the children and young people had half or fewer seizures with the diet compared 6% with the group not assigned to the diet. Two large trials of the Modified Atkins Diet compared to a non-diet control had similar results, with over 50% of children having half or fewer seizures with the diet compared to around 10% in the control group.
The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet that in medicine is used primarily to treat difficult-to-control (refractory) epilepsy in children. The diet forces the body to burn fats rather than carbohydrates. Normally, the carbohydrates contained in food are converted into glucose, which is then transported around the body and is particularly important in fueling brain function. However, if little carbohydrate remains in the diet, the liver converts fat into fatty acids and ketone bodies. The ketone bodies pass into the brain and replace glucose as an energy source. An elevated level of ketone bodies in the blood, a state known as ketosis, leads to a reduction in the frequency of epileptic seizures. Around half of children and young people with epilepsy who have tried some form of this diet saw the number of seizures drop by at least half, and the effect persists even after discontinuing the diet. Some evidence indicates that adults with epilepsy may benefit from the diet, and that a less strict regimen, such as a modified Atkins diet, is similarly effective. Potential side effects may include constipation, high cholesterol, growth slowing, acidosis, and kidney stones.
In 1921, Rollin Turner Woodyatt reviewed the research on diet and diabetes. He reported that three water-soluble compounds, β-hydroxybutyrate, acetoacetate, and acetone (known collectively as ketone bodies), were produced by the liver in otherwise healthy people when they were starved or if they consumed a very low-carbohydrate, high-fat diet. Dr. Russell Morse Wilder, at the Mayo Clinic, built on this research and coined the term "ketogenic diet" to describe a diet that produced a high level of ketone bodies in the blood (ketonemia) through an excess of fat and lack of carbohydrate. Wilder hoped to obtain the benefits of fasting in a dietary therapy that could be maintained indefinitely. His trial on a few epilepsy patients in 1921 was the first use of the ketogenic diet as a treatment for epilepsy.
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