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).
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.
A survey in 2005 of 88 paediatric neurologists in the US found that 36% regularly prescribed the diet after three or more drugs had failed, 24% occasionally prescribed the diet as a last resort, 24% had only prescribed the diet in a few rare cases, and 16% had never prescribed the diet. Several possible explanations exist for this gap between evidence and clinical practice. One major factor may be the lack of adequately trained dietitians who are needed to administer a ketogenic diet programme.
Based on this, researchers from the University of Alabama conducted a study with a small group of obese men with prediabetes. They compared a form of intermittent fasting called “early time-restricted feeding,” where all meals were fit into an early eight-hour period of the day (7 am to 3 pm), or spread out over 12 hours (between 7 am and 7 pm). Both groups maintained their weight (did not gain or lose) but after five weeks, the eight-hours group had dramatically lower insulin levels and significantly improved insulin sensitivity, as well as significantly lower blood pressure. The best part? The eight-hours group also had significantly decreased appetite. They weren’t starving.