Epilepsy’s Big, Fat Miracle [food tie-in]

[Guest guest]

This ran last month - I missed it to post ...

Epilepsy's Big, Fat Miracle

By FRED VOGELSTEIN

http://www.nytimes.com/2010/11/21/magazine/21Epilepsy-t.html?ref=health & pagewant\

ed=print

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, , or I will make an exception.

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 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 Mc'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.

, 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. 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 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.

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. ph 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. "

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, , 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 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 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. 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. s 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 , became experts themselves. Jim, a Hollywood director

and producer, read about the diet in an epilepsy book and called the author, Dr.

Freeman, at s 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 , Charlie Abrahams's dietitian at s 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.

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 s 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 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.