Epilepsy is one of the most common neurological disorders after stroke, and affects around 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 can 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 (not yielding to treatment) when two or three anticonvulsant drugs have failed to control it. About 60% of patients achieve control of their epilepsy with the first drug they use, whereas around 30% do not achieve control with drugs. When drugs fail, other options include epilepsy surgery, vagus nerve stimulation, and the ketogenic diet.
Normal dietary fat contains mostly long-chain triglycerides (LCTs). Medium-chain triglycerides (MCTs) are more ketogenic than LCTs because they generate more ketones per unit of energy when metabolised. Their use allows for a diet with a lower proportion of fat and a greater proportion of protein and carbohydrate, leading to more food choices and larger portion sizes. The original MCT diet developed by Peter Huttenlocher in the 1970s derived 60% of its calories from MCT oil. Consuming that quantity of MCT oil caused abdominal cramps, diarrhea, and vomiting in some children. A figure of 45% is regarded as a balance between achieving good ketosis and minimising gastrointestinal complaints. The classical and modified MCT ketogenic diets are equally effective and differences in tolerability are not statistically significant. The MCT diet is less popular in the United States; MCT oil is more expensive than other dietary fats and is not covered by insurance companies.
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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.
Although many hypotheses have been put forward to explain how the ketogenic diet works, it remains a mystery. Disproven hypotheses include systemic acidosis (high levels of acid in the blood), electrolyte changes and hypoglycaemia (low blood glucose). Although many biochemical changes are known to occur in the brain of a patient on the ketogenic diet, it is not known which of these has an anticonvulsant effect. The lack of understanding in this area is similar to the situation with many anticonvulsant drugs.
First reported in 2003, the idea of using a form of the Atkins diet to treat epilepsy came about after parents and patients discovered that the induction phase of the Atkins diet controlled seizures. The ketogenic diet team at Johns Hopkins Hospital modified the Atkins diet by removing the aim of achieving weight loss, extending the induction phase indefinitely, and specifically encouraging fat consumption. Compared with the ketogenic diet, the modified Atkins diet (MAD) places no limit on calories or protein, and the lower overall ketogenic ratio (about 1:1) does not need to be consistently maintained by all meals of the day. The MAD does not begin with a fast or with a stay in hospital and requires less dietitian support than the ketogenic diet. Carbohydrates are initially limited to 10 g per day in children or 20 g per day in adults, and are increased to 20–30 g per day after a month or so, depending on the effect on seizure control or tolerance of the restrictions. Like the ketogenic diet, the MAD requires vitamin and mineral supplements and children are carefully and periodically monitored at outpatient clinics.
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Our bodies are incredibly adaptive to what you put into it – when you overload it with fats and take away carbohydrates, it will begin to burn ketones as the primary energy source. Optimal ketone levels offer many health, weight loss, physical and mental performance benefits.1There are scientifically-backed studies that show the advantage of a low-carb, ketogenic diet over a low-fat diet. One meta-analysis of low-carbohydrate diets showed a large advantage in weight loss. The New England Journal of Medicine study resulted in almost double the weight loss in a long-term study on ketone inducing diets.
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When I recently asked Hall what his research tells us about weight loss with the ketogenic diet, he said simply: “The idea is that low-carb, ketogenic diets cause your body to burn way more calories, resulting in a lot of weight loss, even if you eat more than you were eating before. But our studies, as well as many others, demonstrate nothing of the sort.”
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This seminal randomized trial, published in JAMA in 2007, involved 300 women and measured their weight loss on the Atkins diet compared to the Zone, Learn, and Ornish diets. The researchers found that while women on Atkins shed a few more pounds, the weight loss on low-carb diets was “likely to be at least as large as for any other dietary pattern” and “the magnitude of weight loss [on Atkins] was modest, with a mean 12-month weight loss of only 4.7 kg.” In other words, long-term weight loss on Atkins wasn’t meaningfully different from the other diets.
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Infants and patients fed via a gastrostomy tube can also be given a ketogenic diet. Parents make up a prescribed powdered formula, such as KetoCal, into a liquid feed. Gastrostomy feeding avoids any issues with palatability, and bottle-fed infants readily accept the ketogenic formula. Some studies have found this liquid feed to be more efficacious and associated with lower total cholesterol than a solid ketogenic diet. KetoCal is a nutritionally complete food containing milk protein and is supplemented with amino acids, fat, carbohydrate, vitamins, minerals and trace elements. It is used to administer the 4:1 ratio classic ketogenic diet in children over one year. The formula is available in both 3:1 and 4:1 ratios, either unflavoured or in an artificially sweetened vanilla flavour and is suitable for tube or oral feeding. Other formula products include KetoVolve and Ketonia. Alternatively, a liquid ketogenic diet may be produced by combining Ross Carbohydrate Free soy formula with Microlipid and Polycose.
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The benefits for the participants following the very low-carb diets weren’t nearly as dramatic as keto proponents claim. While the participants saw their insulin levels drop and stay low, they only saw a small increase in calorie burn, and that waned over time. (That short-lived increase in calorie burn amounted to about 100 extra calories per day — much less than the 400 to 600 calories promised by low-carb gurus.)
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The original therapeutic diet for paediatric epilepsy provides just enough protein for body growth and repair, and sufficient calories[Note 1] to maintain the correct weight for age and height. The classic therapeutic ketogenic diet was developed for treatment of paediatric epilepsy in the 1920s and was widely used into the next decade, but its popularity waned with the introduction of effective anticonvulsant medications. This 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 nuts, 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 classic 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.
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The nerve impulse is characterised by a great influx of sodium ions through channels in the neuron's cell membrane followed by an efflux of potassium ions through other channels. The neuron is unable to fire again for a short time (known as the refractory period), which is mediated by another potassium channel. The flow through these ion channels is governed by a "gate" which is opened by either a voltage change or a chemical messenger known as a ligand (such as a neurotransmitter). These channels are another target for anticonvulsant drugs.
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While research supports the idea that consuming moderate amounts of caffeine is a good thing, the science suggests that the benefits are seen primarily in coffee and tea, two plant-based beverages with antioxidants. So while some of these supplements attempt to do the same (Ketoburn provides beta carotene), consuming supplemental forms of antioxidants simply does not have the same biochemical effect as drinking them in their most natural form. Plus, there's no guarantee that antioxidants are really in there as the FDA doesn’t regulate supplements.
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It usually takes three to four days for your body to go into ketosis because you have to use up your body's stores of glucose, i.e., sugar first, Keatley says. Any major diet change can give you some, uh, issues, and Keatley says he often sees patients who complain of IBS-like symptoms and feeling wiped out at the beginning of the diet. (The tiredness happens because you have less access to carbs, which give you quick energy, he explains.)
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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 Henry 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 P. Howland, the parent of one of Conklin's successful patients and a wealthy New York corporate lawyer, gave his brother John Elias Howland a gift of $5,000 to study "the ketosis of starvation". As professor of paediatrics at Johns Hopkins Hospital, John E. Howland used the money to fund research undertaken by neurologist Stanley Cobb and his assistant William G. Lennox.