Biology 202
2000 First Web Report
On Serendip

Epilepsy is a disorder affecting approximately one in every two hundred people. (2) Epileptic seizures begin when one or more unstable neurons fire in an uncontrollable manner. This occurs when the neuronal membrane is made particularly sodium permeable in an area that is not supposed to have increased sodium permeability. As the neurons fire, the signal spreads until it encompasses part or all of the brain. Seizures vary from partial, which involve only part of the brain and may not cause unconsciousness, to generalized, which involve the entire brain, and an almost certain loss of consciousness. The initial neuronal instability may be due to many factors including inherent genetic instability of proteins in ion pumps or channels, metabolic abnormalities like low blood glucose or high alcohol concentration, and physical factors like head trauma or a brain tumor. (3)

The most common treatment of epilepsy is through the use of medications known as anticonvulsants or anti-epileptic drugs (AEDs). Most of the original medications used to treat epilepsy were first discovered by serendipity. However, as science begins to understand more about the function of neurons, more carefully planned studies are being launched to target specific substrates. Some effective AEDs target excitatory neurotransmitters like glutamine and compromise them, while others work to improve the ability of inhibitory neurotransmitters like GABA. However, many of these medications have severe side effects like nausea, vomiting, loss of appetite and irregular hair growth, and most are teratogenic, so cannot be administered to a pregnant woman. In addition, because the cause of epilepsy is not really understood, there is no guarantee that every or even any AED will be effective in any given patient. One alternative treatment, particularly useful in young children with seizures that do not respond to medication is the use of a ketogenic diet. (1)

It has long been known that starvation is an effective, if impractical means of controlling seizures. There is even a reference in the Bible to starvation controlling "fits." The first scientific study of fasting as a treatment for epilepsy was conducted in France in 1910. The researchers concluded that seizures were improved by absolute starvation. (2)

During starvation, the body first burns all of its glycogen. It then begins to burn body fat and protein for the specific purpose of supplying the brain with glucose. As fasting continues, the body shifts into a state known as ketosis. The brain begins to use ketones from the metabolism of fats as energy rather than glucose. This shift in metabolism also correlates with a reduction in seizure activity. (2)

In 1912, Wilder was the first to use a high-fat, low-carbohydrate diet to prolong ketosis in Mayo Clinic patients with diabetes. Around the same time, Howland and Gamble of Johns Hopkins Department of Pediatrics observed that "prayer and a water diet" for three to four weeks reduced "fits" in the nephew of a professor of pediatrics. Suspecting that prayer was not the key to recovery, they began to investigate the effects of starvation. By the 1930s, a diet much like the modern ketogenic diet was being used widely to treat patients with seizures. However, after World War II, with the emergence of antiepileptic drugs, the use of the diet declined. Since the middle of the 1980s, use of a ketogenic diet, particularly to treat very young patients has increased markedly. (2)

The goal of the ketogenic diet is to shift the primary metabolism from carbohydrates to fats and thus to keep the body in a prolonged state of ketosis. The classic diet, which is still closely followed in the United States calls for a ratio of four to one of fats to proteins plus carbohydrates. A typical meal may consist of a small portion of vegetables or fruit, a protein source, and a large helping of heavy whipping cream. A variant of this diet known as the medium chain triglyceride (MCT) diet also limits carbohydrates, but supplements with MCT oil derived from coconuts which is more quickly digested than most fats, and allow for a more normal lifestyle that the rather tedious classic version. Both versions call for decreased total calories and fluid intake to avoid excess fat being flushed from the system in favor of carbohydrates. (2)

The unusually high fat content of the ketogenic diet induces ketosis by denying the body the carbohydrates it needs for normal metabolism. This metabolic shift increases the seizure "threshold" in some patients, presumably by action at the synapse. (4) The diet is approximately as effective as most available drug therapies. About one third of patients are greatly improved, one third are slightly improved, and one third show no improvement or adverse effects. The most successful group is young children. There are many claims that the diet is not effective in older children or adults. However, there are few valid studies to support this claim. The effect on adults has yet to be thoroughly investigated. (6) There is an initiative into research examining a link between metabolism in the brain and seizure control in response to the success of this diet. (5)

The ketogenic diet is obviously not the most convenient method available for treating epilepsy. However, in cases where medications have proved ineffective, or the side effects are unbearable, it is a solid alternative that has proven itself as a safe and effective treatment. Moreover, as opposed to chemical treatments, the diet takes advantage of a naturally occurring process, so although there are some side effects, they tend to be less severe than those associated with antiepiliptic medications. As more is discovered about the physiology of the brain, we may be better able to understand why the diet is so effective and devise treatments that are not so disruptive to a normal lifestyle.

WWW Sources

2) An introduction to the Ketogenic Diet

3) What is Epilepsy all About

4) Frequently Asked Questions about the Ketogenic Diet

5); How does a ketosis inducing diet prevent/treat epileptic seizures?

6) Diets & Supplements

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