It is possible to combine the results of several small studies to produce evidence that is stronger than that available from each study alone—a statistical method known as meta-analysis. One of four such analyses, conducted in 2006, looked at 19 studies on a total of 1,084 patients. It concluded that a third achieved an excellent reduction in seizure frequency and half the patients achieved a good reduction.
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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.
The ketogenic diet is usually initiated in combination with the patient's existing anticonvulsant regimen, though patients may be weaned off anticonvulsants if the diet is successful. Some evidence of synergistic benefits is seen when the diet is combined with the vagus nerve stimulator or with the drug zonisamide, and that the diet may be less successful in children receiving phenobarbital.
Long-term use of the ketogenic diet in children increases the risk of slowed or stunted growth, bone fractures, and kidney stones. The diet reduces levels of insulin-like growth factor 1, which is important for childhood growth. Like many anticonvulsant drugs, the ketogenic diet has an adverse effect on bone health. Many factors may be involved such as acidosis and suppressed growth hormone. About one in 20 children on the ketogenic diet develop kidney stones (compared with one in several thousand for the general population). A class of anticonvulsants known as carbonic anhydrase inhibitors (topiramate, zonisamide) are known to increase the risk of kidney stones, but the combination of these anticonvulsants and the ketogenic diet does not appear to elevate the risk above that of the diet alone. The stones are treatable and do not justify discontinuation of the diet. Johns Hopkins Hospital now gives oral potassium citrate supplements to all ketogenic diet patients, resulting in one-seventh of the incidence of kidney stones. However, this empiric usage has not been tested in a prospective controlled trial. Kidney stone formation (nephrolithiasis) is associated with the diet for four reasons:
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.
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Because the ketogenic diet alters the body's metabolism, it is a first-line therapy in children with certain congenital metabolic diseases such as pyruvate dehydrogenase (E1) deficiency and glucose transporter 1 deficiency syndrome, which prevent the body from using carbohydrates as fuel, leading to a dependency on ketone bodies. The ketogenic diet is beneficial in treating the seizures and some other symptoms in these diseases and is an absolute indication. However, it is absolutely contraindicated in the treatment of other diseases such as pyruvate carboxylase deficiency, porphyria, and other rare genetic disorders of fat metabolism. Persons with a disorder of fatty acid oxidation are unable to metabolise fatty acids, which replace carbohydrates as the major energy source on the diet. On the ketogenic diet, their bodies would consume their own protein stores for fuel, leading to ketoacidosis, and eventually coma and death.
The remaining calories in the keto diet come from protein — about 1 gram (g) per kilogram of body weight, so a 140-pound woman would need about 64 g of protein total. As for carbs: “Every body is different, but most people maintain ketosis with between 20 and 50 g of net carbs per day,” says Mattinson. Total carbohydrates minus fiber equals net carbs, she explains.
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And while some fats can be healthy, there’s a risk that in following a high-fat diet, you’ll increase your intake of unhealthy trans and saturated fats. These “bad” fats are found in things like red meat, poultry skin, cheese, and butter, and can lead to an increase in LDL, or “bad” cholesterol and increased risk of heart disease. (14) This is a controversial issue, as some experts do recommend adopting a low-carbohydrate diet to lower heart disease risk. If you’re at risk or have heart disease, it’s important to speak with your doctor first about your health needs.
Short-term results for the LGIT indicate that at one month approximately half of the patients experience a greater than 50% reduction in seizure frequency, with overall figures approaching that of the ketogenic diet. The data (coming from one centre's experience with 76 children up to the year 2009) also indicate fewer side effects than the ketogenic diet and that it is better tolerated, with more palatable meals.
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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This can look different for everybody, but some popular forms of this are the 16:8 diet, where you fast for 16 hours (usually from dinnertime until a late breakfast) and eat all your food within an eight-hour span. Another is the 5:2 diet, where you eat less than 500 calories for two non-consecutive days a week and then eat normally for the rest of the week.
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.