Friday, November 19, 2010

Epilepsy’s Big, Fat Miracle - Ketogenic diet as treatment

Epilepsy’s Big, Fat Miracle - NYTimes.com

Starvation had long been one approach to treating epilepsy. Deny the patient food for, say, a week and often their seizures went away. But there were obvious limits on how long starvation could be used as a treatment. In the 1920s, researchers at the Mayo Clinic, looking for a way to treat diabetics, figured out that it was not fasting per se that helped control seizures. Rather, they found that it was what the body did during an extended fast that helped control them. Deprived of food, the human body starts burning body fat as fuel, and it was that process of ketosis that somehow had the antiepileptic effect. Trick the body into thinking it was starving by taking away its primary fuel of carbohydrates and forcing it to subsist on an all-fat diet, and you could create that antiepileptic effect as long as necessary.

The diet was quickly adopted and widely used through the 1930s. And then, almost as fast as it had appeared, the keto diet disappeared. When Dilantin was first used as an antiepileptic drug in 1938, its success steered medical minds toward pharmaceutical solutions. A generation later, the diet had been all but forgotten. There was no scientific evidence that it worked, after all. More important, it was incredibly difficult to administer. Even in the 1990s, Millicent Kelly, Charlie Abrahams’s dietitian at Johns Hopkins, was planning menus with a calculator and a legal pad.

By 2000, more people were asking about keto, but most pediatric neurologists still would not prescribe it. That bias seemed ridiculous to J. Helen Cross, the principal investigator of the 2008 randomized keto trial at University College London. “I’d been dealing with complex epilepsy cases for 10 years, and it was quite clear to me that certain children did respond to the ketogenic diet,” Cross says. “But we in our institution — and I know we weren’t alone — were coming up against barriers to get the resources to do it. They’d say there’s no evidence it works. It’s a quack diet. There is no controlled data. So I wanted to prove that it did work once and for all, and do it in a way so that people couldn’t argue with it.”

It took five years to enroll and track enough patients to make the study credible and another two years to analyze the data and undergo the rigorous academic peer-review process. But since the study was published in 2008, it has answered doubts about keto’s clinical effectiveness.

Keto has now attracted attention from all corners of the neurological community. Two scientists at the National Institutes of Health are planning a study of its effectiveness in Parkinson’s patients. Papers published in the past two years suggest that keto may slow the growth of a brain tumor in mice. A biotechnology company named Accera is marketing a high-fat powder to Alzheimer’s patients that is supposed to reproduce the effects of ketosis, without the dietary restrictions of keto.

Still, there is one giant unanswered question: Why does keto work? Jong Rho, the head of pediatric neurology at the University of Calgary and the Alberta Children’s Hospital, theorizes that ketone bodies — the compounds made by the liver when the body burns fat for energy — protect brain cells from being damaged. Rho, who just received a $2 million, five-year grant from the National Institutes of Health to continue to investigate this theory, says experiments with epileptic mice suggest that extended time on the diet makes them more seizure-resistant.

Rho’s theory, however, only raises more questions. How would ketone bodies protect brain cells? Scientists don’t have a clue about how our cells react during ketosis. They don’t even know how much ketone bodies themselves matter. Until scientists understand the basic biological mechanisms, they can’t begin to embark on the long and costly process of drug development.

The success of the pediatric diet seems to have made it easier for keto scientists to get money for this basic research. “Before Helen’s study, we all had a clear sense that keto worked,” says Carl Stafstrom, the head of pediatric neurology at the University of Wisconsin, “but we couldn’t say in a grant proposal that the diet has been proven to be effective. Now we can.” There are recently financed studies, for example, exploring why the body resists ketosis and exploring compounds that might trigger the antiepileptic mechanism.

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There has been so much buzz around keto that neurologists and scientists have begun wondering what else it can do. Could it be used to treat seizures in adults? What about Parkinson’s, Alzheimer’s, A.L.S. and certain cancers? Tumors typically need glucose to grow. There is very little of this simple sugar in a keto diet, and there have been interesting results with mice that suggest the diet might slow tumor growth. These scientific explorations are in their early stages and may not amount to much. Nonetheless, researchers are taking them seriously.

Fantastic article on the ketogenic diet for the treatment of epilepsy.

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