Epilepsy’s Big, Fat Miracle
Stephen Lewis for The New York Times; Food Stylist: Brett Kurzweil
By FRED VOGELSTEIN
Published: November 17, 2010
Once every three or four months my son, Sam, grabs a cookie or a piece of candy and, wide-eyed, holds it inches from his mouth, ready to devour it. He knows he’s not allowed to eat these things, but like any 9-year-old, he hopes that somehow, this once, my wife, Evelyn, or I will make an exception.
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Tierney Gearon for The New York Times
FAMILY CIRCLE Sam’s twin sister, Beatrice, also has epilepsy.
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We never make exceptions when it comes to Sam and food, though, which means that when temptation takes hold of Sam and he is denied, things can get pretty hairy. Confronted with a gingerbread house at a friend’s party last December, he went scorched earth, grabbing parts of the structure and smashing it to bits. Reason rarely works. Usually one of us has to pry the food out of his hands. Sometimes he ends up in tears.
It’s not just cookies and candy that we forbid Sam to eat. Cake, ice cream, pizza, tortilla chips and soda aren’t allowed, either. Macaroni and cheese used to be his favorite food, but he told Evelyn the other day that he couldn’t remember what it tastes like anymore. At Halloween we let him collect candy, but he trades it in for a present. At birthday parties and play dates, he brings a lunchbox to eat from.
There is no crusade against unhealthful food in our house. Some might argue that unhealthful food is all we let Sam eat. His breakfast eggs are mixed with heavy cream and served with bacon. A typical lunch is full-fat Greek yogurt mixed with coconut oil. Dinner is hot dogs, bacon, macadamia nuts and cheese. We figure that in an average week, Sam consumes a quart and a third of heavy cream, nearly a stick and a half of butter, 13 teaspoons of coconut oil, 20 slices of bacon and 9 eggs. Sam’s diet is just shy of 90 percent fat. That is twice the fat content of a McDonald’s Happy Meal and about 25 percent more than the most fat-laden phase of the Atkins diet. It puts Sam at risk of developing kidney stones if he doesn’t drink enough. It is constipating, so he has to take daily stool softeners. And it lacks so many essential nutrients that if Sam didn’t take a multivitamin and a calcium-magnesium supplement every day, his growth would be stunted, his hair and teeth would fall out and his bones would become as brittle as an 80-year-old’s.
Evelyn, Sam’s twin sister Beatrice and I don’t eat this way. But Sam has epilepsy, and the food he eats is controlling most of his seizures (he used to have as many as 130 a day). The diet, which drastically reduces the amount of carbohydrates he takes in, tricks his body into a starvation state in which it burns fat, and not carbs, for fuel. Remarkably, and for reasons that are still unclear, this process — called ketosis — has an antiepileptic effect. He has been eating this way for almost two years.
Curiosity bordering on alarm is the only way to describe how people receive this information. “In-teresting,” one acquaintance said. “Did you make this up yourself?” Another friend was more direct: “Is this a mainstream-science thing or more of a fringe treatment?” We are not surprised by these reactions. What we are doing to Sam just seems wrong. The bad eating habits of Americans, especially those of children, are a national health crisis. Yet we are intentionally feeding our son fatty food and little else.
But what we are doing is mainstream science. Elizabeth Thiele, the doctor who prescribed and oversees Sam’s diet, is the head of the pediatric epilepsy program at Massachusetts General Hospital for Children, which is affiliated with Harvard Medical School. In fact, the regimen, known as the ketogenic diet, is now offered at more than 100 hospitals in the United States, Canada and other countries. We’re not opposed to drugs; we tried many. But Sam’s seizures were drug-resistant, and keto, the universal shorthand, often provides seizure control when drugs do not.
The idea of food as medicine has been a controversial topic in this country in recent years. For decades the fight that the late Robert Atkins and his low-carb acolytes had with mainstream medicine has been as vitriolic as a religious war. There are food cures for everything from cancer and heart disease to cataracts. Doctors talk about diet as a part of basic good health all the time. But talk to them about a diet instead of drugs to stop an infection or treat a tumor and most would be visibly alarmed, and in many cases, they would have good reason to be. A decade ago most doctors held the same contempt for keto. An Atkins-like diet that worked as well — and often better — than antiepileptic drugs? Common sense suggests that’s crazy.
But when it comes to keto’s impact on pediatric seizures, there is wide acceptance. There are about two dozen backward-looking analyses of patient data suggesting keto works, and, more significant, two randomized, controlled studies published in 2008. One of the trials, by researchers at University College London, found that 38 percent of patients on the diet had their seizure frequency reduced more than 50 percent and that 7 percent had their seizure frequency reduced more than 90 percent.
Those numbers may look low, but they’re not. These were patients for whom antiepileptic drugs had already failed. For children with certain kinds of drug-resistant seizures, Thiele’s clinical data show an even better response: 7 out of 10 were able to reduce their count more than 90 percent with the diet. Those statistics are as good as those for any antiepileptic drug ever made. Other pediatric neurologists get similar results. The diet has cut Sam’s seizures by 75 percent.
That is a big deal. There are dozens of antiepileptic drugs on the market, many approved in the last 15 years. The newer ones work with fewer side effects, and that’s important. But the percentage of patients who take drugs and still have seizures hasn’t changed meaningfully in decades. About a third of the nearly 3 million epileptics in the United States have drug-resistant seizures, and doctors estimate that at least 250,000 of those drug-resistant patients are children. Since keto often works when drugs do not, neurologists finally see a way to fix that problem.
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.
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Stephen Lewis for The New York Times; Food Stylist: Brett Kurzweil
Breakfast, lunch, dinner and snack: ingredients for a typical meal for Sam Vogelstein.
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Food as part of disease treatment is slowly being accepted by more doctors. Many think it is new. But it is not. During the first half of the 20th century, the impact of food on our bodies was one of the hottest scientific fields. Insulin was discovered in 1921, and its commercial production meant survival for diabetics. In the 1930s, three scientists won a Nobel Prize for discovering that a substance in raw liver cured pernicious anemia, a disease that was almost always fatal. Eight Nobels were awarded just for work related to vitamins. And, it turns out, the ketogenic diet was developed back in the early part of the last century, too, only to disappear from medical literature for two generations.
Our family’s introduction to keto came in February 2009, when we flew to Boston to see Thiele and Heidi Pfeifer, a dietitian who works with her, at Mass General. Joseph Sullivan, our neurologist at the University of California, San Francisco, told us that Thiele and Pfeifer were doing cutting-edge work. And we needed cutting-edge help. We tried 11 seizure drugs, and Sam was hospitalized twice during the previous year. Yet we were still struggling to keep Sam’s seizure count below 10 per hour. Every day, seven days a week, during the 13 hours he was awake, he would have between 100 and 130 seizures.
Nothing did any good. Some drugs, because of the side effects, actually did him harm. One drug gave him hand tremors, another made him a zombie and a third made him hallucinate, thinking that bugs and worms were crawling out of his skin.
I hit my low point the night we took Sam home from his second hospitalization in six months. He had been seizing almost nonstop for more than a week despite being on four medications. So after keeping him home from school for a week and having daily conversations with Sullivan, we decided to admit him for what Sullivan called a “reset.” The thinking is that, like a computer, doctors can reboot a person’s brain to reduce or stop seizures. They knocked Sam out with Ativan for 15 hours and monitored his brain waves. The following day he was discharged, seizing just as frequently, and, for his bravery, sporting a head-to-toe body rash from a reaction to a medication.
The best way to think about a seizure is to imagine an electrical storm. Our brains and bodies are normally full of electricity. The brain generates biochemical electrical charges, allowing brain cells, nerves and muscles to communicate. A seizure happens when this electricity surges out of control and overloads parts of the brain’s circuitry.
Sam doesn’t have grand mal seizures — the kind you see in movies — but a form of what’s known as petit mal, or absence seizures. Instead of falling down and twitching for minutes, Sam loses consciousness for short 5-to-20-second bursts. Grand mal and many other seizure types — there are dozens — often leave the sufferer exhausted. Sam’s seizures are more like hitting the pause button on a DVD. He stops and stares vacantly. His jaw slackens. And his head and torso lean forward slightly, bobbing rhythmically. Then it’s over, as if it had never happened. He is not disoriented, tired or in pain. If he was in the middle of a sentence, he would finish it. If he was going hand-over-hand on the monkey bars, he would pause without falling. It is not like a faint, when you go limp. Part of his brain has momentarily shut down. Though Sam says that he is sometimes aware when he is having a seizure, typically his only clue is that when he comes to, everything around him has shifted slightly. A lot more happens in 10 seconds than we think.
His seizures didn’t start this way. Epilepsy was first diagnosed in 2005, when Sam was just shy of 5. The diagnosis then was myoclonic epilepsy. Each day he would have about half a dozen spells that looked as if he had been touched by a cattle prod. Each was a strong, 45-degree snap forward at the waist. After a few tries, we found a medication that controlled them.
The absence seizures started at the end of 2007. We tried first to treat them by increasing the dose of the seizure drug he was already on. But by the end of March 2008 he was having more, not fewer, seizures, and by early fall he was having trouble finishing a sentence. His teachers watched out for him and told the class about what was going on. But it’s hard to learn math or reading when you’re receiving life on the other end of a bad cell-phone connection.
Swimming? Bike riding? Soccer team? Forget it. Sam couldn’t even cry without interruption: he would stub a toe or skin a knee; cry for 15 seconds; have a 15-second seizure; and then continue sobbing. Sam had trouble even watching a movie. Once after seeing “Speed Racer” at home, he said: “Dad, I think the DVD is scratched. When I was watching, it kept leaving words out.”
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We were desperate, and frankly, despite advances, the ketogenic diet is still only for the desperate. For Sam’s diet to be effective, he must eat a certain number of calories every day with specific ratios of fat, protein and carbohydrates. These are not back-of-the-envelope calculations, but ratios that have to be hit exactly at every meal. If Sam wants a snack after school, he gets 18 grams of bacon (about two slices), 14 grams of macadamia nuts (about seven nuts) and 18 grams of apple (less than an eighth). In keto-speak that’s 3.04 grams of fat to every gram of protein and carbs combined. A snack using the ratios of the typical American diet — about 30 percent fat, 15 percent protein, 55 percent carbs — would have twice the protein, a third the fat and eight times the carbs.
To jump through these arithmetic hoops, Evelyn, who gave up her career to take on the now full-time job of feeding Sam, plans meals on the kitchen computer using a Web-based program called KetoCalculator. It is hard to imagine how to administer keto without it. A meal for Sam might have eight ingredients. Mathematically, there are potentially millions of combinations — a bit more of this; a bit less of that — that gets you to a 400-calorie meal and a 3-to-1 ratio. KetoCalculator does the math. Every ingredient — butter, cream, bacon, oil, eggs, nuts and fruit — is weighed to the 10th of a gram on an electronic jeweler’s scale. When Evelyn comes up with a recipe that works, she hits “print” and files it in a black loose-leaf binder. We now have more than 200 recipes.
Doing all this once is fascinating. Who knew that a cup of milk had more carbs than half a slice of toast or that macadamia nuts have more than twice the fat of pork rinds? But administering the diet for three meals and two snacks a day, seven days a week for two years is relentless. There is no “Let’s just order pizza” in our house, no matter how crazy the week has been. A barbecue at a friend’s house takes Evelyn 30 minutes of prep time. A sleepover takes two hours, because she labels all the food and writes out heating and serving instructions for the parents. Evelyn spent six hours preparing food for a three-day camping trip in August. Unexpected events that barely register in most families — like the fact that I recently ate the applesauce that was to be part of Sam’s breakfast — create mad scrambles to recalculate and reweigh meals so Sam gets out the door on time.
The diet is administered like medicine, and parents need to work with their neurologist and a keto dietitian to come up with an appropriate caloric intake for the child. You receive a log-in to KetoCalculator, which is only available through a clinician. Every three months, Sam’s height and weight are measured, and a baseline blood test is administered. This medical oversight lessens the worry that we are going to poison Sam with all the fat he eats. Children can fall into ketoacidosis — essentially overdoing keto. It’s rare, and easily reversible, but it can be fatal if you don’t know what to look for.
Ultimately what makes the diet so stressful is that on top of all the gross recipes and weird mechanics, there is no margin for error. Just as you can’t take blood-pressure medicine sporadically or vary its dose day to day, on keto you can’t just dump beaten eggs into a pan; you have to take a rubber spatula and scrape out the two or three grams that typically adhere to the measuring bowl. Then Sam needs to finish every bite of every meal. (Two other, somewhat less restrictive diets are also being prescribed for epileptic children, but neither worked as well for Sam.) The penalty for cheating, at least in Sam’s case, is seizures. During the first few weeks on the diet, a friend in his carpool shared a piece of toast. We lost seizure control for a week. Miraculously, Sam has done this only once.
Will the diet doom Sam to a lifetime of heart disease and high cholesterol? Thiele and Pfeifer don’t think so. There is research, published this year, suggesting that there are few lingering effects in the years after stopping the diet. Johns Hopkins Children’s Hospital in Baltimore, where the diet was pioneered in the 1920s, surveyed 101 former patients, most of whom had been off the diet for more than six years, and found that they had normal cholesterol and cardiovascular levels, no preference for fatty foods and, for those off the diet the longest, normal growth rates.
Certainly Sam’s appearance shows no sign that he is eating so much fat. There are reports that the diet can stunt children’s growth even if they are on vitamin supplements. But Sam started the diet when he was 4 feet 3 inches tall and weighed 51 pounds. He is now 4 feet 8 inches tall and 68 pounds. His cholesterol and related measures of fat in the bloodstream are elevated, as is typical for children on the diet. But the other tests are normal.
We don’t know how long Sam will be on this diet. It won’t be forever. Most who respond stay on it for about two years — which for Sam would be in April. But there is no magic number. I’ve read about some children who started in infancy and were on the diet for more than five years. Typically the diet is stopped at one of three junctures: when children have been seizure-free for two years; when they outgrow their seizures, as about 60 percent do; or when families decide the sacrifices required to stay on the diet have become too onerous.
If you want to see someone who has been on the ketogenic diet, look up Charlie Abrahams on YouTube. The video to look for is his speech to some 300 doctors, dietitians and researchers at the International Symposium on Dietary Therapy for Epilepsy and Other Neurological Disorders. When Charlie was a baby, his doctors diagnosed Lennox-Gastaut Syndrome, a particularly severe form of epilepsy that if not properly treated often leaves sufferers permanently brain damaged.
Drugs did nothing, and so, like many parents of children with serious illnesses, his parents, Jim and Nancy, became experts themselves. Jim, a Hollywood director and producer, read about the diet in an epilepsy book and called the author, Dr. John Freeman, at Johns Hopkins Medical Institution. In 1993 Freeman was the only doctor in the country using the diet consistently. He had been using it since 1969 and claimed that 30 percent of his patients were seizure-free. The idea seemed ridiculous to Charlie’s neurologist and most of the medical community at the time. The only thing you could stop with that much fat was your heart. “Flip a coin — I don’t think either will work,” his son’s neurologist said when Abrahams asked about trying keto or an herbal remedy he had also read about.
With nothing to lose, the Abrahamses put their son on the diet just after Thanksgiving in 1993. Three days later his seizures stopped. He was on the diet for four years and hasn’t had another seizure since. Today, at 18, Charlie is getting ready to graduate from high school.
The diet effectively cured a very sick child, but it only made an impact because Jim Abrahams made sure the rest of the world heard about it. He filmed a video about his experience starring his friend, Meryl Streep. “Dateline NBC” did a segment on Charlie in 1994, which led to an avalanche of media interest and letters from patients. At the same time, Abrahams started the Charlie Foundation to Help Cure Pediatric Epilepsy, an organization whose sole mission is to enable the diet to be administered in every hospital worldwide.
All this publicity led patients to ask their doctors about the diet; doctors started experimenting with it and recording their results; and as e-mail and Internet databases became widely available, word spread at an accelerating rate. In 1997, 15 hospitals were offering keto to epileptic children; now roughly 150 do, Abrahams says.
What astonished Abrahams and helped drive his effort to publicize the diet was that keto was not a new idea. It was first used as a medical treatment for epilepsy in the 1920s. The principles underlying the diet have been around since Hippocrates touched on them nearly 2,500 years ago. 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.
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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.
All of this still puts us a long way from anything remotely resembling a pill that would replace the keto diet. Being able to eat normally — or even close to normally — is critical to expanding the benefits of the ketogenic diet beyond the roughly 3,500 pediatric epilepsy patients currently on it. There are few adults who could adhere to a diet like the one Sam is on.
For now the main alternatives to keto are the Modified Atkins Diet (MAD), published by Johns Hopkins in 2003, and Thiele and Pfeifer’s Low Glycemic Index Treatment (L.G.I.T.), published in 2005. MAD is more restrictive than the Atkins diet that people use for weight loss, but nonetheless a bit easier to follow than keto because it allows more protein; L.G.I.T. is easier than keto because it allows more carbs and protein as long as the carbs are like strawberries — which affect blood sugar slowly — and not like bread, potatoes or candy, which make it spike. There are volumes of clinical data supporting the effectiveness of these diets, but not yet the kind of randomized, controlled study that show these diets work as well as keto, and keto is still most often prescribed. We started Sam on L.G.I.T., moved to MAD and are now at keto. For the moment it seems to work best for him.
Sam isn’t seizure-free yet, but he’s so close that you might think he was. From well over 100 seizures a day, Sam now typically has fewer than 6. Keto got us most of the way there, but not all the way. The diet cut his seizures to roughly 30 a day, and two drugs, added separately to make sure we were changing only one variable at a time, did the rest. Sam is finally a happy, healthy and independent kid.
He’s learning to skateboard and swim out of the shallow end. We’re about to teach him to ride a bike. In June he made me go on the 100-foot free-fall ride at an amusement park. He loved it. (I loved it less.) He and his friends Nick and Ethan spend almost every weekend searching for portals to other worlds. And he leaves people who meet him to wonder if he isn’t one of the bravest and most disciplined kids they have ever met.
The truth is that as much control as Evelyn and I think we exert over Sam’s life — especially what he eats — we both understand that the person who is truly in charge of his health is Sam. Most days he and his Batman lunchbox are out of the house from 7 in the morning until 4 in the afternoon. At lunch, at class birthdays — everywhere he goes, really — there is the temptation to quite reasonably say, “I would like to eat and drink like all the other kids.” But he doesn’t. Instead, on his own, he politely says: “I’m not supposed to eat that. It gives me seizures.”
That doesn’t mean he likes it. He hates the diet. For his 10th birthday in May, he wants to go off keto; and we are going to try to honor that request. Will he start to seize uncontrollably again? In March, we found out that Sam’s twin sister, Beatrice, had epilepsy, too. At the moment, it’s completely controlled with medication. Will she grow out of it like many children do? Will Sam? Like all parents in our situation, we hope so. But we don’t know. At least we can comfort ourselves with the idea that we are participating in a grand exploration of the link between metabolism and brain chemistry that over the years may find some answers. That, at least, takes away some of the bad taste of this lousy diet.
Fred Vogelstein, a contributing editor for Wired, is writing a book about the intersection of technology and media in Silicon Valley.
A version of this article appeared in print on November 21, 2010, on page MM51 of the Sunday Magazine.
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