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.[7]
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]
Normal dietary fat contains mostly long-chain triglycerides (LCTs). Medium-chain triglycerides (MCTs) are more ketogenic than LCTs because they generate more ketones per unit of energy when metabolised. Their use allows for a diet with a lower proportion of fat and a greater proportion of protein and carbohydrate,[18] leading to more food choices and larger portion sizes.[4] The original MCT diet developed by Peter Huttenlocher in the 1970s derived 60% of its calories from MCT oil.[15] Consuming that quantity of MCT oil caused abdominal cramps, diarrhea, and vomiting in some children. A figure of 45% is regarded as a balance between achieving good ketosis and minimising gastrointestinal complaints. The classical and modified MCT ketogenic diets are equally effective and differences in tolerability are not statistically significant.[9] The MCT diet is less popular in the United States; MCT oil is more expensive than other dietary fats and is not covered by insurance companies.[18]
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]
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]
In 1921, Rollin Turner Woodyatt reviewed the research on diet and diabetes. He reported that three water-soluble compounds, β-hydroxybutyrate, acetoacetate, and acetone (known collectively as ketone bodies), were produced by the liver in otherwise healthy people when they were starved or if they consumed a very low-carbohydrate, high-fat diet.[10] Dr. Russell Morse Wilder, at the Mayo Clinic, built on this research and coined the term "ketogenic diet" to describe a diet that produced a high level of ketone bodies in the blood (ketonemia) through an excess of fat and lack of carbohydrate. Wilder hoped to obtain the benefits of fasting in a dietary therapy that could be maintained indefinitely. His trial on a few epilepsy patients in 1921 was the first use of the ketogenic diet as a treatment for epilepsy.[10]
A study with an intent-to-treat prospective design was published in 1998 by a team from the Johns Hopkins Hospital[20] and followed-up by a report published in 2001.[21] As with most studies of the ketogenic diet, no control group (patients who did not receive the treatment) was used. The study enrolled 150 children. After three months, 83% of them were still on the diet, 26% had experienced a good reduction in seizures, 31% had had an excellent reduction, and 3% were seizure-free.[Note 7] At 12 months, 55% were still on the diet, 23% had a good response, 20% had an excellent response, and 7% were seizure-free. Those who had discontinued the diet by this stage did so because it was ineffective, too restrictive, or due to illness, and most of those who remained were benefiting from it. The percentage of those still on the diet at two, three, and four years was 39%, 20%, and 12%, respectively. During this period, the most common reason for discontinuing the diet was because the children had become seizure-free or significantly better. At four years, 16% of the original 150 children had a good reduction in seizure frequency, 14% had an excellent reduction, and 13% were seizure-free, though these figures include many who were no longer on the diet. Those remaining on the diet after this duration were typically not seizure-free, but had had an excellent response.[21][22]
We’ve now arrived at tip number 16. If you’re still having trouble losing weight, despite following the 15 pieces of advice listed above, it might be a good idea to bring out the heavy artillery: optimal ketosis. Many people stalling at weight plateaus while on a low-carb diet have reported finding optimal ketosis helpful. It’s what can melt the fat off once again.
The Mayo Clinic Diet is the official diet developed by Mayo Clinic, based on research and clinical experience. It focuses on eating healthy foods that taste great and increasing physical activity. It emphasizes that the best way to keep weight off for good is to change your lifestyle and adopt new health habits. This diet can be tailored to your own individual needs and health history — it isn't a one-size-fits-all approach.
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