The Johns Hopkins Hospital protocol for initiating the ketogenic diet has been widely adopted.[43] It involves a consultation with the patient and their caregivers and, later, a short hospital admission.[19] Because of the risk of complications during ketogenic diet initiation, most centres begin the diet under close medical supervision in the hospital.[9]

Early studies reported high success rates; in one study in 1925, 60% of patients became seizure-free, and another 35% of patients had a 50% reduction in seizure frequency. These studies generally examined a cohort of patients recently treated by the physician (a retrospective study) and selected patients who had successfully maintained the dietary restrictions. However, these studies are difficult to compare to modern trials. One reason is that these older trials suffered from selection bias, as they excluded patients who were unable to start or maintain the diet and thereby selected from patients who would generate better results. In an attempt to control for this bias, modern study design prefers a prospective cohort (the patients in the study are chosen before therapy begins) in which the results are presented for all patients regardless of whether they started or completed the treatment (known as intent-to-treat analysis).[19]
The first modern study of fasting as a treatment for epilepsy was in France in 1911.[12] Twenty epilepsy 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.[13]
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.[18][50]
The Mayo Clinic Diet provides practical and realistic ideas for including more physical activity and exercise throughout your day — as well as finding a plan that works for you. The diet recommends getting at least 30 minutes of exercise every day and even more exercise for further health benefits and weight loss. The diet also emphasizes moving more throughout the day, such as taking the stairs instead of an elevator.
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.[57] 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.[56]
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.)
Con: Results can vary depending on how much fluid you drink. By drinking more water, you dilute the concentration of ketones in the urine and thus a lower level of ketones will be detected on the strips. The strips don’t show a precise ketone level. Finally, and most importantly, as you become increasingly keto-adapted and your body reabsorbs ketones from the urine, urine strips may become unreliable, even if you’re in ketosis.
Avoid sweetened drinks. Drinks that are sweetened, whether artificially or naturally, will have little nutritional value and add lots of empty calories to your diet. Do not drink fruit juice or other sweetened drinks. Even natural sugars will increase your daily calorie intake and prevent weight loss. If you chose to drink juice, do not exceed 4 oz per day (1/2 cup). Instead of drinking sweetened beverages throughout your day, drink unsweetened, calorie-free beverages. Some beverages to avoid include:
Work indulgence foods into your calorie plan. If you do want to have something that is a little higher in calories, then make sure that you work it into your overall calorie goal for the day. For example, if you are following a 1,800 calorie plan, and you want to have a brownie that is 300 calories, then you would only have 1,500 calories left for the day.
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).[19] 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.[56]
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.[7]
For patients who benefit, half achieve a seizure reduction within five days (if the diet starts with an initial fast of one to two days), three-quarters achieve a reduction within two weeks, and 90% achieve a reduction within 23 days. If the diet does not begin with a fast, the time for half of the patients to achieve an improvement is longer (two weeks), but the long-term seizure reduction rates are unaffected.[44] Parents are encouraged to persist with the diet for at least three months before any final consideration is made regarding efficacy.[9]
There are many ways in which epilepsy occurs. Examples of pathological physiology include: unusual excitatory connections within the neuronal network of the brain; abnormal neuron structure leading to altered current flow; decreased inhibitory neurotransmitter synthesis; ineffective receptors for inhibitory neurotransmitters; insufficient breakdown of excitatory neurotransmitters leading to excess; immature synapse development; and impaired function of ionic channels.[7]
Here’s what we do know: The keto diet may be useful in treating symptoms of epilepsy, a seizure disorder. “The use of keto in treating epilepsy has the most evidence,” Angelone says. One study conducted by Johns Hopkins Medicine, for example, followed epileptic patients on the keto diet and found that 36 percent of them had a 50 percent reduction in seizures after three months on the diet, and 16 percent were seizure-free. However, experts aren't entirely sure why the keto diet has this affect, she adds.
The ketogenic diet is indicated as an adjunctive (additional) treatment in children and young people with drug-resistant epilepsy.[26][27] It is approved by national clinical guidelines in Scotland,[27] England, and Wales[26] and reimbursed by nearly all US insurance companies.[28] Children with a focal lesion (a single point of brain abnormality causing the epilepsy) who would make suitable candidates for surgery are more likely to become seizure-free with surgery than with the ketogenic diet.[9][29] About a third of epilepsy centres that offer the ketogenic diet also offer a dietary therapy to adults. Some clinicians consider the two less restrictive dietary variants—the low glycaemic index treatment and the modified Atkins diet—to be more appropriate for adolescents and adults.[9] A liquid form of the ketogenic diet is particularly easy to prepare for, and well tolerated by, infants on formula and children who are tube-fed.[5][30]
When you’re eating the foods that get you there (more on that in a minute), your body can enter a state of ketosis in one to three days, she adds. During the diet, the majority of calories you consume come from fat, with a little protein and very little carbohydrates. Ketosis also happens if you eat a very low-calorie diet — think doctor-supervised, only when medically recommended diets of 600 to 800 total calories.
This principle involves eating low-energy-dense foods and can help you lose weight by feeling full on fewer calories. Healthy choices in each of the other food groups in moderate amounts make up the rest of the pyramid — including whole-grain carbohydrates, lean sources of protein such as legumes, fish and low-fat dairy, and heart-healthy unsaturated fats.
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