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.
The brain is composed of a network of neurons that transmit signals by propagating nerve impulses. The propagation of this impulse from one neuron to another is typically controlled by neurotransmitters, though there are also electrical pathways between some neurons. Neurotransmitters can inhibit impulse firing (primarily done by γ-aminobutyric acid, or GABA) or they can excite the neuron into firing (primarily done by glutamate). A neuron that releases inhibitory neurotransmitters from its terminals is called an inhibitory neuron, while one that releases excitatory neurotransmitters is an excitatory neuron. When the normal balance between inhibition and excitation is significantly disrupted in all or part of the brain, a seizure can occur. The GABA system is an important target for anticonvulsant drugs, since seizures may be discouraged by increasing GABA synthesis, decreasing its breakdown, or enhancing its effect on neurons.
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: