Food for thought: The ketogenic diet as epilepsy treatment

Newswise — While ketogenic diets have been used to treat epilepsy for the last 100 years, they are now finding a resurgence of interest. The diets shift the body’s energy source from glucose to ketones, mimicking the physiological effects of fasting; Hippocrates noted that fasting could reduce seizure frequency (see timeline below).

A boy named Charlie and a sea change

The classic ketogenic diet gained popularity in the 1920s and 1930s, but its presence faded with the availability of more anti-seizure medications, which had fewer lifestyle restrictions. As recently as 25 years ago, the ketogenic diet was rarely used as a treatment for epilepsy.

At that time, Johns Hopkins (USA) was one of the few institutions offering the classic ketogenic diet (90% of calories from fat, 7% from protein and only 3% from carbohydrates) as treatment for pediatric epilepsy. They met with families from many areas of the country—and around the world—who could not find a local physician to offer the diet.

“There were many doctors who told families they didn’t believe in it and that it was too hard,” said Eric Kossoff, professor of neurology and pediatrics at the Johns Hopkins University School of Medicine.

But families had started to seek treatments for refractory epilepsy that might improve seizure control, and perhaps with fewer adverse effects than medications. Neurologists began to gradually accept the ketogenic diet as a valid treatment option in those situations. Much of the shift hinged on the publicity surrounding a single patient: Charlie Abrahams, a 2-year-old boy with drug-resistant epilepsy and cognitive decline.

Charlie was treated with the ketogenic diet in 1994. He became seizure free within a month, spent several years on the diet and never had another seizure. (He is now 28.) Charlie’s father, Jim Abrahams, formed The Charlie Foundation to increase awareness of the ketogenic diet, and in 1994 Charlie’s story was featured on a US television program called NBC Dateline, which resulted in thousands of phone calls to the Charlie Foundation from parents seeking more information for their children with drug-resistant epilepsy.

Abrahams also directed a film depicting the family’s experience, First Do No Harm (1997), and the Charlie Foundation supported the first prospective trial of the classic ketogenic diet, which was published in 1998.

Since then, ketogenic diets have become increasingly studied and accepted as a pillar of epilepsy treatment. “The ketogenic is mainstream, it is everywhere,” said Eric Kossoff, professor of neurology at Johns Hopkins. “It’s one of the four major ways we treat epilepsy, along with medication, surgery and nerve stimulation.”

Some skepticism remains, however, said Kossoff. “There are some neurologists who are not as familiar with it, or who are not willing to prescribe it.”

Types of ketogenic diets

Due to its very high fat requirement, the classical KD can be difficult to maintain. Less restrictive alternatives appear to be nearly as effective while providing more food choice. These alternatives include the modified Atkins diet (MAD; also called the modified ketogenic diet), the medium-chain triglyceride (MCT) diet, and low glycemic index therapy (LGIT) (see table).

Do the diets work?

Published in 1998, the first KD trial included 51 children who were enrolled at 7 sites. Eighty-eight percent of the children remained on the diet after 3 months, 69% remained on it at 6 months, and 47% remained on it at 1 year. Three months after initiating the diet, 54% of children had at least a 50% decrease in seizure frequency. At 1 year, 10% of patients were seizure free.

Another 1998 study followed 150 children between age 1 and 16. Collectively, they averaged 410 seizures per month. Three months after starting the diet, 32% of the children had at least a 90% decrease in seizures. After a year, 55% of children were still on the diet; of those, 27 % had at least a 90% decrease in seizures.

Since then, other studies have collectively shown that up to 55% of children achieve seizure freedom with classical KD after 3 months, and 85% achieve seizure reduction. The first randomized clinical trial, published in 2008, included 145 children randomized to dietary treatment or usual care . After three months, 38% of the diet group had greater than a 50% seizure reduction, compared with 6% in the usual-care group, and 7% of the diet group had a 90% or greater reduction in seizures, compared with 0% in the control group. “This study justifies consideration of the KD alongside any other anti-epileptic drug (AED) in the treatment of drug resistant epilepsy,” wrote the authors.

Though few studies have compared the various diet types, a recent randomized trial found that in 158 children, median seizure reductions were 66% on classical KD, 45% on Modified Atkins diet (MAD) and 54% on low-glycemic-index treatment (LGIT) after 24 weeks. Similar numbers of children across the three treatments experienced at least a 50% reduction in seizures.

The trial also showed that changes in seizure burden were more gradual with LGIT than with the other two diets, but the rate of adverse effects was lowest in the LGIT group. LGIT is considered the least restrictive diet of the three, which may make long-term adherence more likely.

“There is increasing evidence that the ketogenic diet, in whatever form may be most practical for the individual, may be effective where drugs have failed across the age range,” said Helen Cross, The Prince of Wales’s Chair of Childhood Epilepsy and Head of Programme in Clinical Neurosciences at the Great Ormond Street Institute of Child Health at University College London, and senior author of the 2008 randomized trial.

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