Weight-loss resistance can often be due to an underlying hormone imbalance. Leptin resistance occurs when your brain stops recognizing leptin's signals to use your body’s fat stores for energy. This causes your body to continually store fat instead of using it. Intermittent fasting has been shown to improve chronic inflammation that can dull the brain’s leptin receptor sites.
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.[23] It concluded that a third achieved an excellent reduction in seizure frequency and half the patients achieved a good reduction.[18]
You can have a completely smooth transition into ketosis, or…not. While your body is adapting to using ketones as your new fuel source, you may experience a range of uncomfortable short-term symptoms. These symptoms are referred to as “the keto flu.” Low-sodium levels are often to blame for symptoms keto flu, since the kidneys secrete more sodium when you’re in ketosis, says Volek. A few side effects:
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.[10][14]
Epilepsy is one of the most common neurological disorders after stroke,[7] and affects around 50 million people worldwide.[8] 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.[7]
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.[19] 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.[18]

Physicians of ancient Greece treated diseases, including epilepsy, by altering their patients' diet. An early treatise in the Hippocratic Corpus, On the Sacred Disease, covers the disease; it dates from c. 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.[Note 3] 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.[Note 4] The royal physician Erasistratus declared, "One inclining to epilepsy should be made to fast without mercy and be put on short rations."[Note 5] Galen believed an "attenuating diet"[Note 6] might afford a cure in mild cases and be helpful in others.[11]

The Mayo Clinic Diet is designed to help you lose up to 6 to 10 pounds (2.7 to 4.5 kilograms) during the initial two-week phase. After that, you transition into the second phase, where you continue to lose 1 to 2 pounds (0.5 to 1 kilogram) a week until you reach your goal weight. By continuing the lifelong habits that you've learned, you can then maintain your goal weight for the rest of your life.