When dietary carbohydrate is broken down into the energy substrate glucose, thereby raising blood glucose levels, the pancreas is stimulated to secrete insulin (the hormone that stores fat and inhibits ketone production). However, when carbohydrate intake is restricted, insulin remains suppressed, and the body’s primary fuel source shifts from glucose to fat, priming the body to enter a state of ketosis. When fat oxidation/breakdown is increased to a certain extent, ketones are made in the liver through a process known as ketogenesis (i.e., keto + genesis = ketone formation). When carbohydrate intake is restricted, blood glucose and insulin levels decrease, which allows fat stores to be broken down rapidly for energy. Most cells in the body can utilize either fatty acids or ketones for fuel, including the brain, which has shown to be more efficient in the presence of ketones rather than glucose.
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.[18]

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]
Around this time, Bernarr Macfadden, an American exponent of physical culture, popularised the use of fasting to restore health. His disciple, the osteopathic physician Dr. Hugh William Conklin of Battle Creek, Michigan, began to treat his epilepsy patients by recommending fasting. Conklin conjectured that epileptic seizures were caused when a toxin, secreted from the Peyer's patches in the intestines, was discharged into the bloodstream. He recommended a fast lasting 18 to 25 days to allow this toxin to dissipate. Conklin probably treated hundreds of epilepsy patients with his "water diet" and boasted of a 90% cure rate in children, falling to 50% in adults. Later analysis of Conklin's case records showed 20% of his patients achieved freedom from seizures and 50% had some improvement.[10]