H. Guldbrand, B. Dizdar, B. Bunjaku, T. Lindström, M. Bachrach-Lindström, M. Fredrikson, C. J. Östgren, F. H. Nystrom, “In Type 2 Diabetes, Randomisation to Advice to Follow a Low-carbohydrate Diet Transiently Improves Glycaemic Control Compared with Advice to Follow a Low-fat Diet Producing a Similar Weight Loss,” Diabetologia (2012) 55: 2118. http://link.springer.com/article/10.1007/s00125-012-2567-4.
When dietary carbohydrate is broken down into the energy substrate glucose, thereby raising blood glucose levels, the pancreas is stimulated to secrete insulin (the hormone that stores fat and inhibits ketone production). However, when carbohydrate intake is restricted, insulin remains suppressed, and the body’s primary fuel source shifts from glucose to fat, priming the body to enter a state of ketosis. When fat oxidation/breakdown is increased to a certain extent, ketones are made in the liver through a process known as ketogenesis (i.e., keto + genesis = ketone formation). When carbohydrate intake is restricted, blood glucose and insulin levels decrease, which allows fat stores to be broken down rapidly for energy. Most cells in the body can utilize either fatty acids or ketones for fuel, including the brain, which has shown to be more efficient in the presence of ketones rather than glucose.
When in the hospital, glucose levels are checked several times daily and the patient is monitored for signs of symptomatic ketosis (which can be treated with a small quantity of orange juice). Lack of energy and lethargy are common, but disappear within two weeks. The parents attend classes over the first three full days, which cover nutrition, managing the diet, preparing meals, avoiding sugar, and handling illness. The level of parental education and commitment required is higher than with medication.
After initiation, the child regularly visits the hospital outpatient clinic where they are seen by the dietitian and neurologist, and various tests and examinations are performed. These are held every three months for the first year and then every six months thereafter. Infants under one year old are seen more frequently, with the initial visit held after just two to four weeks. A period of minor adjustments is necessary to ensure consistent ketosis is maintained and to better adapt the meal plans to the patient. This fine-tuning is typically done over the telephone with the hospital dietitian and includes changing the number of calories, altering the ketogenic ratio, or adding some MCT or coconut oils to a classic diet. Urinary ketone levels are checked daily to detect whether ketosis has been achieved and to confirm that the patient is following the diet, though the level of ketones does not correlate with an anticonvulsant effect. This is performed using ketone test strips containing nitroprusside, which change colour from buff-pink to maroon in the presence of acetoacetate (one of the three ketone bodies).
In most cases, the macronutrient profile for a keto diet for beginners consists of about 5–10% carbohydrates, 15–25% protein, and the remaining 65–80% from fat. By restricting glucogenic substrates (i.e. nutrients that increase blood glucose levels, like carbohydrates and glucogenic amino acids from proteins), a deeper level of ketosis can be achieved, which may have a plethora of benefits as discussed below. As an example, one study compared diets with 30, 60, and 100 grams of carbohydrates per day and found that restricting carbohydrates to 30 grams led to a greater increase in circulating ketone levels and body fat loss.
During the 1920s and 1930s, when the only anticonvulsant drugs were the sedative bromides (discovered 1857) and phenobarbital (1912), the ketogenic diet was widely used and studied. This changed in 1938 when H. Houston Merritt, Jr. and Tracy Putnam discovered phenytoin (Dilantin), and the focus of research shifted to discovering new drugs. With the introduction of sodium valproate in the 1970s, drugs were available to neurologists that were effective across a broad range of epileptic syndromes and seizure types. The use of the ketogenic diet, by this time restricted to difficult cases such as Lennox–Gastaut syndrome, declined further.
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