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Harvard research eyes diet-epilepsy link

For decades doctors have been keenly aware that a diet high in fat and extremely low in carbohydrates can stop epileptic seizures that can't be controlled by medication.

And while doctors broadly knew why the diet worked, some of the finer biological mechanisms involved remained elusive.

Now, a team of Harvard scientists has identified a protein that is active in the brain of epileptics who faithfully follow the so-called ketogenic diet, an eating plan laden with meat, cheese, eggs and other fatty fare.

The diet is purposely low in vegetables, fruits and cereals.

For children on the diet, seizures not only stop in many instances -- they never return. Adults also have had success on this diet and yet another version, called the modified Atkins plan, which also emphasizes fatty, high-protein foods.

"People actually lose weight on the ketogenic diet," said Dr. Mary Andriola, director, child neurology and clinical neurophysiology at Stony Brook University Medical Center. She added that the diet is calorie-controlled and carefully designed.

A diet high in fat has the potential to cause kidney stones, gout and high cholesterol, not to mention weight gain. But because the plan is aimed at keeping calories to a minimum and fats within a range the body can burn off, weight loss becomes possible.

The diet works in epilepsy because it drastically reduces glucose, the primary source of energy in cells and the preferred energy source in the brain. Oddly, glucose in people prone to epilepsy is associated with seizures.

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The ketogenic diet works, Harvard experts say, because it mimics the effects of starvation. When a person is starving, the body is forced into a more primitive method of deriving energy from ketones, the breakdown products of fats. Seizures stop when ketones are the brain's primary energy source.

"I've met a lot of kids whose lives are completely changed by this diet," said Dr. Gary Yellen, a professor of neurobiology at Harvard Medical School and a member of the research team. Working with mice, Yellen and collaborators from the Dana-Farber Cancer Institute found that the newly identified protein controls ketone metabolism in brain cells.

"We realized we had come upon a metabolic switch to do what the ketogenic diet does to the brain without any actual dietary therapy," said Dr. Alfredo Gimenez-Cassina, a research fellow at Dana-Farber.

It's possible to use the protein, he said, as a pharmacological target so that epileptics don't have to be on the diet, but can one day simply take a "a diet pill."

Yellen said while a diet seems like a wholesome way to treat seizures, adherence can be difficult. "Diets in general are hard, and this diet is really hard," he said. "So finding a pharmacological substitute for this would make lots of people really happy."

But pharmaceutical answers to complex disorders, especially one as complicated as epilepsy, may take years, even decades, experts say. Until a pill that functions effectively -- and safely -- in the brain is developed, high-fat diets will remain the most likely course for thousands of people with drug-resistant epilepsy.

The diet has been prescribed for years at Stony Brook, said Andriola, who added that many families have found ways to achieve success with it by having all family members consume the same foods. "I've seen a lot of dads who love the steak, although no potatoes, and having eggs and bacon for breakfast," she said.

Andriola describes the diet as one of the oldest effective treatments for epilepsy.

The dietary program owes its development to doctors in the 1920s, working independently at Johns Hopkins University and the Mayo Clinic.

Physicians at both institutions accurately deciphered what was happening chemically in the brain following observations of Bernard Macfadden, a flamboyant faith healer of the era who put people with epilepsy on regimens of prayer and fasting. His epilepsy "cures" attracted a huge following. As long as fasting lasted -- and he deprived people of food for weeks -- even those with the severest forms of the disorder remained seizure-free. When normal eating resumed, seizures returned.

Medical historians believe Macfadden likely read two key biblical references. According to Matthew 17:14-21 and Mark 9:14-29, while speaking to disciples, Jesus extolled the virtues of prayer and fasting as effective treatments for a condition that can be interpreted to be epilepsy.

The Hopkins and Mayo Clinic experts were the first to figure out that ketone production can be maintained by a high-fat diet and without starving a person to death. "I have had people who have had seizure control and they also lost weight and initially were very happy with that improvement," Andriola said of patients on a ketogenic diet.

Desserts and other carb-laden fare, Andriola said, became too tempting. "They would say, 'I don't like seizures, but I do like cookies and cake and pizza.' "

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