Dec 5, 2017

High-fat, Low-carb Ketogenic Diet, Other Non-Drug Therapies May Provide Seizure Relief in Children with Hard-to-treat Epilepsy

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Embargoed until noon on Dec. 4, 2017

WASHINGTON, D.C. – New research provides hope for the 1 in 5 children whose seizures aren’t controlled by antiepileptic drugs (AEDs), the standard of care for this disease. Children who are not candidates for traditional epilepsy surgery may benefit from the high-fat, low-carbohydrate ketogenic diet, vagal nerve stimulation (VNS) or a procedure to separate the two halves of the brain, suggests the first research to compare the three therapies, which is being presented at the American Epilepsy Society 71st Annual Meeting.

Other research being presented at the meeting suggests slowly implementing the ketogenic diet might make it more tolerable while still controlling seizures.

“If two different AEDs aren’t beneficial in a child with epilepsy, chances that other medications will work are pretty low,” said Dave F. Clarke, M.D., M.B.B.S., senior author of the study on alternatives to AEDs, and professor of the Baylor College of Medicine and clinical director of epilepsy at Texas Children’s Hospital, Houston. “Unfortunately, many doctors keep trying medications without considering alternatives. Children whose seizures aren’t controlled after trying two AEDs need to go to a specialized epilepsy center which can offer other options and provide the expertise to implement them safely.”


Many children with AED-resistant epilepsy benefit from an alternate therapy, according to a study at Dell Children’s Medical Center of Central Texas in Austin. The alternatives in the study were the ketogenic diet, implantation of a VNS – a “pacemaker for the brain” that prevents seizures by sending mild pulses of electrical energy to the vagus nerve, which has connections to the brain – and corpus callosotomy surgery, which prevents seizures from spreading by severing a major connection between the two halves of the brain. The study is the first to compare the therapies and assess parental satisfaction with how well they control seizures and improve quality of life.

The study included 210 children who tried one or more of the three alternatives: 98 followed the ketogenic diet, 150 had VNS and 44 had the surgery. Researchers interviewed their parents using a nine-item questionnaire to assess benefits, side effects and quality of life. In the study, the ketogenic diet the children followed typically featured a 3:1 or 4:1 ratio (3 or 4 grams of fat to every 1 gram combination of protein and carbohydrates).

Parents reported a 50 percent or greater reduction in seizures in 63 percent of children who went on the ketogenic diet, 54 percent of those who had the surgery and 52 percent of those who had VNS. They reported improvements in quality of life among 48 percent of those on the diet, 63 percent who had the surgery and 44 percent who had VNS. Overall, 80 percent of parents whose children were on the ketogenic diet or had the VNS reported they were satisfied with treatment, as were 75 percent of those whose children had the surgery.

The ketogenic diet flips the proportions of the typical American diet so that the majority of the diet includes fat, rather than carbohydrates. This pushes the body into a metabolic state called ketosis, forcing it to use fat (rather than carbohydrates) as an energy source. Ketosis changes the way brain cells use energy, helping reduce seizures, although researchers aren’t sure why.

“Based on the parents’ feedback, I would suggest doctors introduce the concept of alternatives after two AEDs fail to control seizures,” said Dr. Clarke, who, along with Miriam Jackson, Jeff Titus and colleagues, conducted the research at Dell Children’s Medical Center of Central Texas. “If a prolonged electroencephalogram (EEG) can identify where the seizures are coming from, surgery to ablate or remove that area of the brain might be an option. If not, doctors really should talk to parents about the diet, VNS or surgery. If parents think the diet can be tolerated, trying it first may not be a bad option.”


When children are placed on the ketogenic diet, they typically are hospitalized and the amount of fat in their diet is quickly increased while carbohydrates are decreased. But a new study from McMaster Children’s Hospital in Hamilton, Ontario, suggests slow implementation at home is easier and that the strictest version of the diet may be unnecessary. This could make the diet easier to tolerate and maintain.

Children typically are placed on a fast, followed by rapid implementation of the diet with a ratio of 4:1 (4 grams of fat to 1 gram of protein/carbohydrates). This diet can lead to problems such as hypoglycemia (low blood sugar) and acidosis (buildup of acid), which is why the diet usually is begun in the hospital. And because it is so restrictive (little to no bread, pasta, etc.), it can be very challenging for families to maintain.

In the study, 40 children (ages 5 months to 16 years old) who had tried at least two AEDs without significant benefit began the ketogenic diet at home, starting with a ratio of 0.67:1 to 1:1. If seizures were controlled and the diet tolerated, the ratio of fats to carbohydrates and protein remained unchanged. If seizures were not controlled, the ratio of fats to carbohydrates was increased gradually every two to three weeks. On average, the patients settled on a ratio of 1.5:1 or 2:1.

Parents were asked to keep seizure diaries for their children and reported the results during healthcare visits. The frequency of seizures decreased from an average of 90 a month before the diet to 24 per month six months after the diet began. At six months, 19 children (48 percent) had more than a 50 percent reduction in seizures, 9 (23 percent) had a more than 90 percent reduction in seizures and 6 (15 percent) were seizure-free. Eight patients discontinued the diet before six months, either because their seizures weren’t controlled or they couldn’t tolerate the diet.

“Changing the way we implement the diet from the most strict to a more liberalized form is more family- and child-friendly and it still works,” said Rajesh RamachandranNair, M.B.B.S., senior author of the study and medical director of the Comprehensive Epilepsy Program at McMaster Children’s Hospital. “The strict protocol that is standard isn’t based on solid evidence, just practice, but the very meager amount of proteins and carbohydrates makes it very difficult to prepare a meal at home. This research suggests you don’t have to aim for that very high ratio.”

Because the ketogenic diet is not nutritionally complete, children need to take vitamins and minerals and may suffer effects such as stunted growth. At McMaster, most children follow the diet for two years and then taper off over three to six months, said Dr. RamachandranNair. In most cases, the seizures do not return, he said.

In both studies, the children continued taking their AEDs, but most were able to reduce the amount they took and a few stopped the medications. Neither study was randomized or controlled. Parents reported the results, meaning some of the assumed benefit may be due to a placebo effect, researchers note.


Davis Renzelmann
Public Communications Inc.

About the American Epilepsy Society

Founded in 1936, the American Epilepsy Society (AES) is a medical and scientific society whose members are dedicated to advancing research and education for preventing, treating and curing epilepsy. AES is an inclusive global forum where professionals from academia, private practice, not-for-profit, government and industry can learn, share and grow to eradicate epilepsy and its consequences.