The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet primarily used to treat difficult-to-control (refractory) epilepsy in children. The diet mimics aspects of starvation by forcing 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 fuelling brain function. However, if there is very little carbohydrate 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.
The diet provides just enough protein for body growth and repair, and sufficient calories to maintain the correct weight for age and height. The classic ketogenic diet contains a 4:1 ratio by weight of fat to combined protein and carbohydrate. This is achieved by excluding high-carbohydrate foods such as starchy fruits and vegetables, bread, pasta, grains and sugar, while increasing the consumption of foods high in fat such as cream and butter.
Most dietary fat is made of molecules called long-chain triglycerides (LCTs). However, medium-chain triglycerides (MCTs)—made from fatty acids with shorter carbon chains than LCTs—are more ketogenic. A variant of the diet known as the MCT ketogenic diet uses a form of coconut oil, which is rich in MCTs, to provide around half the calories. As less overall fat is needed in this variant of the diet, a greater proportion of carbohydrate and protein can be consumed, allowing a greater variety of food choices.
Developed in the 1920s, the ketogenic diet was widely used into the next decade, but its popularity waned with the introduction of effective anticonvulsant drugs. In the mid 1990s, Hollywood producer Jim Abrahams, whose son's severe epilepsy was effectively controlled by the diet, created the Charlie Foundation to promote it. Publicity included an appearance on NBC's Dateline programme and ...First Do No Harm (1997), a made-for-television film starring Meryl Streep. The foundation sponsored a multicentre research study, the results of which—published in 1996—marked the beginning of renewed scientific interest in the diet.
The diet is effective in half of the patients who try it, and very effective in a third. In 2008, a randomised controlled trial showed a clear benefit for treating refractory epilepsy in children with the ketogenic diet. There is some evidence that adults with epilepsy may benefit from the diet, and that a less strict regime, such as a modified Atkins diet, is similarly effective. The ketogenic diet has also been proposed as a treatment for a number of neurological conditions other than epilepsy; as of 2008, research in this area has yet to produce sufficient positive data to warrant clinical use.
Epilepsy
Epilepsy is a common neurological disorder affecting at least 50 million people worldwide. It is diagnosed in a person having recurrent unprovoked seizures. These occur when cortical neurons fire excessively, hypersynchronously, or both, leading to temporary disruption of normal brain function. This might affect, for example, the muscles, the senses, consciousness, or a combination. A seizure might be focal, confined to one part of the brain, or generalised, spread widely throughout the brain and leading to a loss of consciousness. Epilepsy can occur for a variety of reasons; some forms have been classified into epileptic syndromes, most of which begin in childhood. Epilepsy is considered refractory to treatment when two or three anticonvulsant drugs have failed to control it. About 60% of patients will achieve control of their epilepsy with the first drug they use; about 30% do not achieve control with drugs, some of whom may be candidates for epilepsy surgery.
History
The ketogenic diet is a mainstream, nonpharmacologic therapy that was developed to reproduce the success and remove the limitations of the non-mainstream use of fasting to treat epilepsy. Although popular for a while, it was discarded by most academic centres in the 1940s when anticonvulsant drugs became available. Most individuals with epilepsy can successfully control their seizures with medication. However, 20–30% fail to achieve such control despite trying a number of different drugs. For this group, and for children in particular, the diet has once again found a role in epilepsy management.
Fasting
The ancient Greek physicians treated diseases, including epilepsy, by altering their patient's diet. An early treatise concerning epilepsy, On the Sacred Disease , can be found in the Hippocratic Corpus and dates from around 400 BC. Its author argued against the prevailing view that epilepsy was supernatural in origin and cure, and proposed that dietary therapy had a rational and physical basis. In the same collection, the author of Epidemics describes the case of a man whose epilepsy is cured as quickly as it had appeared, through complete abstinence of food and drink. The royal physician, Erasistratus, declared, "One inclining to epilepsy should be made to fast without mercy and be put on short rations." Galen believed an "attenuating diet" might afford a cure in mild cases and be helpful in others.
The first modern study of fasting as a treatment for epilepsy was in France in 1911. Twenty patients, of all ages, were "detoxified" by consuming a low-calorie vegetarian diet, combined with periods of fasting and purging. Two benefited enormously, but most failed to maintain compliance with the imposed restrictions. The diet improved the patients' mental capabilities, in contrast to their medication, potassium bromide, which dulled the mind.
Around this time, the American exponent of physical culture, Bernarr Macfadden, popularised the use of fasting to restore health. His disciple, the osteopathic physician Hugh Conklin, of Battle Creek, Michigan, began to treat his epilepsy patients by recommending fasting. Conklin conjectured that epileptic seizures were caused when a toxin, secreted from the Peyer's patches in the intestines, was discharged into the bloodstream. He recommended a fast lasting 18 to 25 days to allow this toxin to dissipate. Conklin probably treated hundreds of epilepsy patients with his "water diet" and boasted of a 90% cure rate in children, falling to 50% in adults. Later analysis of Conklin's case records showed 20% of his patients achieved freedom from seizures and 50% had some improvement.
Conklin's fasting therapy was adopted by neurologists in mainstream practice. In 1916, a Dr. McMurray wrote to the New York Medical Journal claiming to have successfully treated epilepsy patients with a fast, followed by a starch- and sugar-free diet, since 1912. In 1921, prominent endocrinologist H. Rawle Geyelin reported his experiences to the American Medical Association convention. He had seen Conklin's success first-hand and had attempted to reproduce the results in 36 of his own patients. He achieved similar results despite only having studied the patients for a short time. Further studies in the 1920s indicated that seizures generally returned after the fast. Charles Howland, the parent of one of Conklin's successful patients and a wealthy New York corporate lawyer, gave his brother John a gift of $5,000 to study "the ketosis of starvation". As professor of paediatrics at Johns Hopkins Hospital, John Howland used the money to fund research undertaken by neurologist Stanley Cobb and his assistant William G. Lennox.
Diet
In 1921, Rollin 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. Russel 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 ketones 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.
Wilder's colleague, paediatrician Mynie Peterman, later formulated the classic diet, with a ratio of one gram of protein per kilogram of body weight in children, 10–15 g of carbohydrate per day, and the remainder of calories from fat. Peterman's work in the 1920s established the techniques for induction and maintenance of the diet. Peterman documented positive effects
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