In the 1960s, medium-chain triglycerides (MCTs) were found to produce more ketone bodies per unit of energy than normal dietary fats (which are mostly long-chain triglycerides). MCTs are more efficiently absorbed and are rapidly transported to the liver via the hepatic portal system rather than the lymphatic system. The severe carbohydrate restrictions of the classic ketogenic diet made it difficult for parents to produce palatable meals that their children would tolerate. In 1971, Peter Huttenlocher devised a ketogenic diet where about 60% of the calories came from the MCT oil, and this allowed more protein and up to three times as much carbohydrate as the classic ketogenic diet. The oil was mixed with at least twice its volume of skimmed milk, chilled, and sipped during the meal or incorporated into food. He tested it on 12 children and adolescents with intractable seizures. Most children improved in both seizure control and alertness, results that were similar to the classic ketogenic diet. Gastrointestinal upset was a problem, which led one patient to abandon the diet, but meals were easier to prepare and better accepted by the children. The MCT diet replaced the classic ketogenic diet in many hospitals, though some devised diets that were a combination of the two.
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The ketogenic diet has been studied in at least 14 rodent animal models of seizures. It is protective in many of these models and has a different protection profile than any known anticonvulsant. Conversely, fenofibrate, not used clinically as an antiepileptic, exhibits experimental anticonvulsant properties in adult rats comparable to the ketogenic diet. This, together with studies showing its efficacy in patients who have failed to achieve seizure control on half a dozen drugs, suggests a unique mechanism of action.
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Reduced hunger. Many people experience a marked reduction in hunger on a keto diet. This may be caused by an increased ability of the body to be fueled by its fat stores. Many people feel great when they eat just once or twice a day, and may automatically end up doing a form of intermittent fasting. This saves time and money, while also speeding up weight loss.
The diet calls for consuming high amounts of fat, a moderate amount of protein, and a very limited amount of carbs. It’s usually broken down to 75, 20, and 5 percent of your daily calories, respectively, says Pamela Nisevich Bede, RD, a dietitian with Abbott’s EAS Sports Nutrition in Columbus, Ohio. Compare that with the typical American diet — which is usually 50 to 65 percent carbs — and it’s safe to say this is a completely different way of eating, Nisevich Bede says.
About 20% of children on the ketogenic diet achieve freedom from seizures, and many are able to reduce the use of anticonvulsant drugs or eliminate them altogether. Commonly, at around two years on the diet, or after six months of being seizure-free, the diet may be gradually discontinued over two or three months. This is done by lowering the ketogenic ratio until urinary ketosis is no longer detected, and then lifting all calorie restrictions. This timing and method of discontinuation mimics that of anticonvulsant drug therapy in children, where the child has become seizure-free. When the diet is required to treat certain metabolic diseases, the duration will be longer. The total diet duration is up to the treating ketogenic diet team and parents; durations up to 12 years have been studied and found beneficial.
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On the ketogenic diet, carbohydrates are restricted and so cannot provide for all the metabolic needs of the body. Instead, fatty acids are used as the major source of fuel. These are used through fatty-acid oxidation in the cell's mitochondria (the energy-producing parts of the cell). Humans can convert some amino acids into glucose by a process called gluconeogenesis, but cannot do this by using fatty acids. Since amino acids are needed to make proteins, which are essential for growth and repair of body tissues, these cannot be used only to produce glucose. This could pose a problem for the brain, since it is normally fuelled solely by glucose, and most fatty acids do not cross the blood–brain barrier. However, the liver can use long-chain fatty acids to synthesise the three ketone bodies β-hydroxybutyrate, acetoacetate and acetone. These ketone bodies enter the brain and partially substitute for blood glucose as a source of energy.
It seems strange that a diet that calls for more fat can raise “good” cholesterol and lower “bad” cholesterol, but ketogenic diets are linked to just that. It may be because the lower levels of insulin that result from these diets can stop your body from making more cholesterol. That means you’re less likely to have high blood pressure, hardened arteries, heart failure, and other heart conditions. It's unclear, however; how long these effects last.
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Because people with type 2 diabetes are at an increased risk for cardiovascular disease, there’s a specific concern that the saturated fat in the diet may drive up LDL, or “bad,” cholesterol levels, and further increase the odds of heart problems. If you have type 2 diabetes, talk to your doctor before attempting a ketogenic diet. They may recommend a different weight-loss diet for you, like a reduced-calorie diet, to manage diabetes. Those with epilepsy should also consult their doctor before using this as part of their treatment plan.
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There’s also some evidence that it might help with type 2 diabetes. “An emerging body of research is finding that a keto plan may have some real benefits thanks to its ability to improve the body’s ability to use insulin and also help control appetite, which can result in easier weight loss,” says Karen Ansel, R.D.N., co-author of Healthy in a Hurry.
These findings were backed up in a 2012 study which had obese diabetics follow a ketogenic diet for 12 months. The researchers found lower fasting glucose levels, improved cholesterol markers and improved HA1c readings. Remember, carbs and glucose are not required when on a ketogenic diet, as stable, clean burning energy is sourced from fat. This makes controlling blood sugar levels near foolproof.
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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.
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Low carb, high fat diets have been used for centuries by doctors when working with obese patients. William Banting published the widely popular booklet titled ‘Letter on Corpulence Addressed to the Public’ in 1863. In this booklet he explained how he had slimmed down by eating a diet high in fat void of carbs. The Banting diet was used for decades by individuals looking to lose weight.
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Wilder's colleague, paediatrician Mynie Gustav 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 (improved alertness, behaviour, and sleep) and adverse effects (nausea and vomiting due to excess ketosis). The diet proved to be very successful in children: Peterman reported in 1925 that 95% of 37 young patients had improved seizure control on the diet and 60% became seizure-free. By 1930, the diet had also been studied in 100 teenagers and adults. Clifford Joseph Barborka, Sr., also from the Mayo Clinic, reported that 56% of those older patients improved on the diet and 12% became seizure-free. Although the adult results are similar to modern studies of children, they did not compare as well to contemporary studies. Barborka concluded that adults were least likely to benefit from the diet, and the use of the ketogenic diet in adults was not studied again until 1999.
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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.
The classic ketogenic diet is not a balanced diet and only contains tiny portions of fresh fruit and vegetables, fortified cereals, and calcium-rich foods. In particular, the B vitamins, calcium, and vitamin D must be artificially supplemented. This is achieved by taking two sugar-free supplements designed for the patient's age: a multivitamin with minerals and calcium with vitamin D. A typical day of food for a child on a 4:1 ratio, 1,500 kcal (6,300 kJ) ketogenic diet comprises three small meals and three small snacks:
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There are theoretically no restrictions on where the ketogenic diet might be used, and it can cost less than modern anticonvulsants. However, fasting and dietary changes are affected by religious and cultural issues. A culture where food is often prepared by grandparents or hired help means more people must be educated about the diet. When families dine together, sharing the same meal, it can be difficult to separate the child's meal. In many countries, food labelling is not mandatory so calculating the proportions of fat, protein and carbohydrate is difficult. In some countries, it may be hard to find sugar-free forms of medicines and supplements, to purchase an accurate electronic scale, or to afford MCT oils.
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Children who discontinue the diet after achieving seizure freedom have about a 20% risk of seizures returning. The length of time until recurrence is highly variable, but averages two years. This risk of recurrence compares with 10% for resective surgery (where part of the brain is removed) and 30–50% for anticonvulsant therapy. Of those who have a recurrence, just over half can regain freedom from seizures either with anticonvulsants or by returning to the ketogenic diet. Recurrence is more likely if, despite seizure freedom, an electroencephalogram shows epileptiform spikes, which indicate epileptic activity in the brain but are below the level that will cause a seizure. Recurrence is also likely if an MRI scan shows focal abnormalities (for example, as in children with tuberous sclerosis). Such children may remain on the diet longer than average, and children with tuberous sclerosis who achieve seizure freedom could remain on the ketogenic diet indefinitely.
Another difference between older and newer studies is that the type of patients treated with the ketogenic diet has changed over time. When first developed and used, the ketogenic diet was not a treatment of last resort; in contrast, the children in modern studies have already tried and failed a number of anticonvulsant drugs, so may be assumed to have more difficult-to-treat epilepsy. Early and modern studies also differ because the treatment protocol has changed. In older protocols, the diet was initiated with a prolonged fast, designed to lose 5–10% body weight, and heavily restricted the calorie intake. Concerns over child health and growth led to a relaxation of the diet's restrictions. Fluid restriction was once a feature of the diet, but this led to increased risk of constipation and kidney stones, and is no longer considered beneficial.
In Asia, the normal diet includes rice and noodles as the main energy source, making their elimination difficult. Therefore, the MCT-oil form of the diet, which allows more carbohydrate, has proved useful. In India, religious beliefs commonly affect the diet: some patients are vegetarians, will not eat root vegetables or avoid beef. The Indian ketogenic diet is started without a fast due to cultural opposition towards fasting in children. The low-fat, high-carbohydrate nature of the normal Indian and Asian diet means that their ketogenic diets typically have a lower ketogenic ratio (1:1) than in America and Europe. However, they appear to be just as effective.
Ketosis has been shown to have anti-inflammatory properties while also assisting with pain relief. Reducing glucose metabolism influences pain, so this could be one potential mechanism of action. In the review The Nervous System and Metabolic Dysregulation: Emerging Evidence Converges on Ketogenic Diet Therapy the authors look at numerous ways that a ketogenic diet can assist with pain and inflammation.