Science is constantly trying to get behind the main factors for the obesity epidemic. From our hurried, fast food lifestyle to our laziness and penchant for T.V. watching rather than exercise, it seems relatively clear that, in most cases, the obesity epidemic is a result of our lifestyle choices. But for some, their genetics play a role that may be hard to fight against.
Family reunions let everyone in the family come together and see the role that genetics has played in their life; maybe you have Aunt Bertha’s red hair or Cousin Vinny’s brown eyes. Unfortunately, you can also inherit Uncle Roger’s pot belly and Grandpa Joe’s wide tush. This is because genetics plays a role in your fat cells and where they are stored.
Because of your DNA, you have a genetic predisposition to carry fat cells in the same areas as your family. Since families blend the DNA of many different people, you may take after one side of your family more than another. This could mean that you and your brother have the genetic predisposition to having love handles while your older sister doesn’t.
In addition to your propensity to carry fat in certain places, you’ll find that your body’s response to exercise mimics others in your family as well. If you have the right genes, you may find that you build muscle very quickly when weight training or, if you’re on the unfortunate end, you don’t.
But, what is the role of genes in weight management? Can you manipulate your genes to work for you rather than against you? For some with genetically linked health issues like thyroid problems, medications can be a solution. Medications can help your body run as it should and can pick up the slack for any glands that are impaired due to genetic lineage.
For most people, medication is not the answer. Instead, learning how your body responds to food and exercise if key to fighting your genes and managing your weight. If your family is filled with overweight people, and you see the signs in your own body that this is probably your destiny too, follow these steps to head genetics off at the pass.
Eat right. Cut out sugars, simple carbohydrates (like white rice and white bread), and stay away from fast food. For some, learned eating habits play a bigger role in weight gain than genetics. Be sure to reevaluate the food lessons you’ve learned from your family and try to make the right decisions regarding what goes in your mouth.
Exercise regularly. Ideally, you should exercise for one hour a day, five to six days per week. Unfortunately, real life often gets in the way of this. If you can exercise four times per week for one half hour per work out, you’ll find you can stave off the effects of genetics.
Stick with it. Fighting your genes is not easy and you may find that you have to work harder than others to receive fewer results. Just remember the alternative facing you and stick with it.
Before embarking on any new physical fitness routine or new and improved eating plan, you should consult a physician. In addition to letting you know if the routine you want to try is healthy for you, they may have some other helpful tips to give you. Speaking with a nutritionist about your eating plan will also help you get ideas for variety and make sure that you haven’t included any foods that will hurt your weight management goals rather than help them.
A UC Berkeley team finds that knocking out a key gene, DNA-PK, prevents weight gain from carbs.
By Melissa Healy
March 21, 2009
Imagine you’ve bellied up to the all-you-can-eat pasta bar in Berkeley, only to meet one of the mice from Hei Sook Sul’s Nutritional Science and Toxicology Lab.
If you come here often, you know that loading up on carbohydrates is going to make you pretty chubby. But you notice that your fellow diner — the mouse — is pretty slim. How does he do it?
DNA Weight Control
This lucky mouse has had a gene knocked out of his genome by researchers in Sul’s UC Berkeley lab. The observation that mice without this gene can eat all the carbs they want and stay slim — whereas other mice fed a high-carb diet become fat — leads Sul to conclude that her lab has found a gene that plays a key role in the process of converting carbohydrates to fat. And that discovery points to an important new target for drug developers hoping to find a way to prevent and perhaps even reverse obesity in humans.
The discovery of the gene’s role in obesity was published Friday in the journal Cell.
The gene involved, known as DNA-PK (for DNA-dependent protein kinase), is widely studied for its role in repairing breaks in the DNA — a function that has made it crucial in cancer research and treatment. But Sul said it was a surprise to discover that the same gene has a key role in the liver’s conversion of excess glucose (all that bread, pasta and sugary soda you’ve failed to work off) to fatty acids.
Not only were mice whose DNA-PK gene had been knocked out 40% leaner than normal mice when all were fed a high-carb, low-fat diet; they also had better blood-lipid profiles, suggesting they’d be at lower risk of developing heart disease.
Sul said no one at this point was thinking about gene therapy as a treatment for obesity. Instead, drug developers might look at how the DNA-PK gene calls out other actors to set in motion the conversion of excess calories to fat and find an agent that might disrupt the process.
If they’re successful, you’ll be able to join that mouse at the pasta bar and look just as svelte as he does.
For a few hundred dollars, you can send away for a genetic test from companies that offer personalized nutrition information — and usually vitamin supplements — based on the results.
Decades from now, we may see these services as we now see miracle cures peddled by traveling salesmen in frontier America. Experts at the cutting edge of nutrigenomics say that current commercial products are based on a sliver of insight into the complex, multi-level system that is metabolism. But soon — perhaps, even, within a decade — personalized diets customized as carefully as a bespoke suit may be an everyday consumer reality.
That was the message of “Nutrigenomics, Nutritional Systems Biology and Personalized Nutrition – Truth or SciFi?,” an afternoon panel discussion at BIO. Genetics alone won’t make this happen, said the speakers; it will require an understanding of our metabolites — the substances made by the human body, with the production influenced by both diet, genetics and the emergent properties of different physiological symptoms. This is the purpose of such research as the Human Metabolome Project, which in January published our metabolome’s first draft.
Once scientists understand how our bodily compounds work, they can associate these with physiology — physical and mental health, energy, longevity, and so on. And then — this is where it gets fun! — people will be able to pose for metabolic portraits. Companies will measure, instead of a handful of genes, the metabolic effect of different foods upon each person. They’ll provide a personal list of nutrients; you’ll be able to plug these into dietary software that tells you what to eat. Send the information to a next-generation grocery store, and the basic components of your ideal diet will be delivered to your door.
Blue-sky? Certainly. Would it take some of the romance out of eating? In the picture painted by the scientists, it sure sounds like it. But while scientists may tell us what to eat, they’re not in the business of selling it to us. If the science ever does progress to that level of culinary customization, I’ve no doubt we’ll see a Julia Child of nutrigenomics, an endless line of chefs showing us how to fold our nutrigenomic recipes like so much origami, and we will eat like (healthy) kings.
The new science of nutrigenomics has some answers. It explains why fat and caffeine are worse for some than others
By CHRISTINE GORMAN
Posted Jun. 11, 2006 in Time
You are what you eat, or so the saying goes. But a new generation of molecular biologists is starting to give that old adage a decidedly high-tech twist. By combining the latest discoveries in human genetics with a deeper understanding of the hundreds of compounds found in food, investigators have begun to tease apart some of the more complex interactions between your diet and your DNA. In the process, they hope eventually to give consumers more personalized advice about what to eat and drink to stave off heart disease, cancer and other chronic conditions of aging. “We are trying to put more science behind the nutrition,” says Jose Ordovas, a geneticist at the Friedman School of Nutrition at Tufts. “We want to finally understand why nutrients do what they do and to whom—why a low-fat diet may not work for some but works for others.”
Do you drink three cups or more of coffee a day? Genetic tests can now determine whether you—like approximately 10% to 20% of the population—have a specific genetic variation that makes it harder for your body to absorb calcium in the presence of caffeine, thus increasing your rate of bone loss.
Are you getting enough folic acid, found in beans, peas and fortified grains? Researchers have learned that many people have a genetic predisposition that puts them at greater risk of developing heart disease because they need more folic acid than the average person to maintain normal blood chemistry.
Would a high-fat diet be particularly damaging to your health, given your genetic makeup? About 15% of folks are born with a form of a liver enzyme that causes their HDL, or good cholesterol, level to go down in response to dietary fat. In most people the HDL level goes up, counterbalancing some of the bad effects of dietary fat on LDL—the dangerous cholesterol.
This area of research is so new, there’s still a bit of a debate over what exactly to call it. Nutritional genetics? Nutritional genomics? Nutrigenomics? But by any name, the field is growing fast. Indeed, some start-up companies simply aren’t waiting for all the scientific mysteries and subtleties to be worked out and have begun to offer tests for a limited number of gene-nutrient interactions directly to consumers.
None of those genetic variations are immediately life threatening. In fact, most of them have no apparent effect. The variants are not like the mutations most of us learned about in school—alterations that cause entire genes or series of genes to malfunction and that result in diseases like sickle-cell anemia and cystic fibrosis. Instead the changes nutritional geneticists are looking for are more like normal variations in the correct spelling of a word—say, theatre or theater, depending on whether you speak the Queen’s English or American. “We all have these variants in our genes,” says Ray Rodriguez, a geneticist at the University of California at Davis. “And they affect how we absorb, utilize and store various nutrients.”
In the case of genes, of course, the alphabet contains just four letters, or bases: A, T, C and G (for adenine, thymine, cytosine and guanine). “A gene has millions of bases,” says Dr. Andrew Greenberg, director of the Obesity and Metabolism Laboratory at Tufts University. “We’re trying to find what’s called a single-nucleotide polymorphism, which is a single change in the DNA, a single base.” Sometimes a single-nucleotide polymorphism (or SNP, pronounced snip) leads to the production of a slightly different version of a protein or enzyme. Sometimes that kind of change causes a shift in an individual’s biochemistry or metabolism, but most of the time it doesn’t.
Greenberg’s research is focused on a protein called perilipin, which coats the surface of stored fat in fat cells. “I know perilipin helps regulate the breakdown of fat,” he explains. But Greenberg is trying to find out whether there are normal variations in the gene that codes for perilipin that affect a person’s risk of becoming obese or developing diabetes. In a study conducted with Ordovas of 1,600 people in Valencia, Spain, Greenberg determined that some of the mutations do seem to correspond to a thinner physique and reduced glucose and triglyceride levels. But other variations in the same gene seem to predispose women to be heavier and have less healthy results in blood tests.
That’s the tricky thing about this new, more individualized exploration of genetics. The effect of a polymorphism may vary depending on where in a gene it is found and the influence of other genes. And a particular alteration can have varying effects in different populations. For instance, a variant gene called apolipoprotein E4 seems to increase the risk of developing Alzheimer’s disease if you are Caucasian or Japanese but not if you are a black African. It’s important to know not only the SNPs but also their context to understand “who will respond and who will not respond,” says Ordovas.
And what if you can’t wait until the science is settled? Well, you could always turn to one of the start-up biotech firms that are providing limited genetic testing for about $250. “We have 19 genes we’ve identified that have a clear and defined response to diet and environmental or lifestyle choices,” says Rosalynn Gill-Garrison, a molecular biologist who helped found the Sciona company in 2000. Worried about that caffeine-calcium link? Sciona tests for that, as well as genetic variants that affect insulin sensitivity, cholesterol levels and more.
The test, which is sold online and at some drugstores, is simple. You use a special stick to swab the inside of your cheek, then send the sample off, along with a questionnaire about your diet and lifestyle, to Sciona’s laboratories in New Haven, Conn. Within three weeks, Sciona sends back a standard computerized analysis of your survey answers, with a few highlights from or red flags about the genetic-test results. For example, Gill-Garrison says, the company estimates from the questionnaire the amount of folic acid in your system. Then it tells you what level you should be aiming for, based on the results of your genetic test.
Sciona’s customers are going to have to wait a while for more comprehensive genetic exams. Researchers now have a good reference guide for the 25,000 or so genes of the human genome and the more than 3 million common variants that lurk within those genes. They still need to figure out how all those genetic variables relate to health and disease. Add the fact that food is full of hundreds of bioactive compounds, each of which varies depending on where plants are grown or animals are raised, and you’ve got quite a lot of information to puzzle out. In the end, you’ll probably find out you still need to eat your broccoli. But at least you’ll have a better understanding of why.
Sciona Recommends Dietary Changes Based on Gene Analysis
March 13, 2006
No-carb? Low-carb? Calorie-counting? Those diets are so 20th century. Several experts are saying that the latest dieting trend centers around the humane genome.
Nutrigenomics is the study of food and diet, and how each interacts with specific genes to increase the risk of certain disease. Now one company is offering a home DNA kit to help design a diet with the most recent science.
“This is going to be the most revolutionary new change in nutrition in decades,” said Dr. David Herber of the UCLA Center for Human Nutrition.
On the Sciona diet, dieters swab the inside of their cheek to collect a DNA sample, fill out a questionnaire, and send them both back to Sciona.
The Sciona laboratory analyzes 19 genes that affect bone health, heart health, antioxidant and detoxification, insulin resistance, and inflammation, according to the Sciona Web site. Based on the findings, Sciona recommends several dietary changes to counteract the genetic weaknesses.
“I think the kind of testing that can be done at home today, where you take cheek cells and then send them in an envelope, will give you personal information that will make it more likely that you’ll make the lifestyle changes that you need to make,” Herber said.
Some experts say it may be too soon to tell if nutrigenomics is an effective way to fight fat.
“The biggest issue is that these diets haven’t been tested,” said Dr. Louis Aronne of New York-Presbyterian/Weill Cornell. “So the question, really, is what happens if you put someone on a diet based on the genetic information? And the bottom line is we have no clue that they will be better.”
By Bruce Grierson Published: Sunday, May 4, 2003, NY Times
A trip to the diet doc, circa 2013. You prick your finger, draw a little blood and send it, along with a $100 fee, to a consumer genomics lab in California. There, it’s passed through a mass spectrometer, where its proteins are analyzed. It is cross-referenced with your DNA profile. A few days later, you get an e-mail message with your recommended diet for the next four weeks. It doesn’t look too bad: lots of salmon, spinach, selenium supplements, bread with olive oil. Unsure of just how lucky you ought to feel, you call up a few friends to see what their diets look like. There are plenty of quirks. A Greek co-worker is getting clams, crab, liver and tofu — a bounty of B vitamins to raise her coenzyme levels. A friend in Chicago, a second-generation Zambian, has been prescribed popcorn, kale, peaches in their own juice and club soda. (This looks a lot like the hypertension-reducing ”Dash” diet, which doesn’t work for everyone but apparently works for him.) He is allowed some chicken, prepared in a saltless marinade, hold the open flame — and he gets extra vitamin D because there’s not enough sunshine for him at his latitude. (His brother’s diet, interestingly enough, is a fair bit different.) Your boss, who seems to have won some sort of genetic lottery, gets to eat plenty of peanut butter, red meat and boutique cheeses.
Nobody is eating exactly what you are. Your diet is uniquely tailored. It is determined by the specific demands of your genetic signature, and it perfectly balances your micronutrient and macronutrient needs. Sick days have become a foggy memory. (Foggy memory itself is now treated with extracts of ginkgo biloba and a cocktail of omega-3 fatty acids.)
”Ultimately, the feedback you’ll get will be continuous,” says Wasyl Malyj, an ”informatics” scientist at the University of California at Davis working with the new Center of Excellence for Nutritional Genomics, who is helping me blue-sky here. The appeal of this kind of laser-targeted diet intervention is hard to miss. If you turn out to be among the population whose cholesterol count doesn’t react much to diet, you’ll be able to go ahead and eat those bacon sandwiches. You’ll no longer be spending money on vitamin supplements that aren’t doing anything for you; you’ll take only the vitamins you need, in precisely the right doses. And there’s a real chance of extending your life — by postponing the onset of diseases to which you’re naturally susceptible — without having to buy even a single book by Deepak Chopra.
This, then, is the promise — and the hype — of nutritional genomics, the second wave of personalized medicine to come rolling out of the Human Genome Project (after pharmacogenomics, or designer drugs). The premise is simple: diet is a big factor in chronic disease, responsible, some say, for a third of most types of cancer. Dietary chemicals change the expression of one’s genes and even the genome itself. And — here’s the key — the influence of diet on health depends on an individual’s genetic makeup.
How does that work? Consider what happens, biologically, when we eat a meal. Until quite recently, most scientists thought food had basically one job: it was metabolized to provide energy for the cell. Indeed, that is what happens to most dietary chemicals — but not all of them. Some of them don’t get metabolized at all; instead, the moment they’re ingested, they peel off and become ligands, molecules that bind to proteins involved in ”turning on” certain genes to one degree or another. A diet that’s particularly out of balance, nutritional-genomics scientists say, will cause gene expressions that nudge us toward chronic illness — unless a precisely tailored ”intelligent diet” is employed to restore the equilibrium.
Take genestein, a chemical in soy, which attaches to estrogen receptors and starts regulating genes. Different individuals may have estrogen receptors that react to genestein differently. Genetic variations like that one, some scientists say, help explain why two people can eat exactly the same diet and respond very differently to it — one maintaining his weight, for example, and the other ballooning.
There is a buzz around nutritional genomics at the moment, which is partly a matter of timing. A sea change is under way in the approach scientists are taking to disease — they’re looking less to nature or nurture alone for answers, and more to the interactive symphony of ”systems biology” that nutrigenomics epitomizes.
At the same time, chatter around this new science has been amplified by a controversy. The idea of the biological relevance of race — even its very existence — is hotly debated. And the assumption of real genetic markers that distinguish one ethnic group from another is at the philosophical heart of nutrigenomics.
Here’s the most familiar example: If you’re of Northern European ancestry, you can probably digest milk, and if you’re Southeast Asian, you probably can’t. In most mammals, the gene for lactose tolerance switches off once an animal matures beyond the weaning years. Humans shared that fate as well — until a mutation in the DNA of an isolated population of Northern Europeans around 10,000 years ago introduced an adaptive tolerance for nutrient-rich milk. The likelihood that you tolerate milk depends on the degree to which you have Northern European blood.
”That, essentially, is the model — a very dramatic one,” says Jim Kaput, the founder of NutraGenomics, a biotechnology company. ”As humans evolved, and as our bodies interacted with foods on each of the continents, we sort of self-selected for these naturally occurring variants. And certain populations have variants that, when presented with Western-type food — which is usually fatty and overprocessed and high in calories — pushes them toward disease rather than health.”
Plenty of examples bear out this ill fit between certain cultures and certain diets — suggesting, if not quite proving, some interplay of genes and nutrition: the Japanese who relocated to the United States after World War II soon saw their cholesterol levels soar. The Alaskan Inuit, whose metabolism was perfectly suited to moving around all day, looking for high-fat food, were suddenly saddled with an evolutionary disadvantage when they began living in heated homes and traveling on snowmobiles, and they now show high levels of obesity, diabetes and cardiovascular disease. The Masai of East Africa have developed new health problems since they abandoned their traditional cattle-meat-and-blood-and-milk diet for corn and beans.
The cradle of nutrigenomics is the cradle of humankind itself: the original migration out of Africa created widely separated subpopulations with distinct collections of gene variants. The members of each subpopulation tend to respond similarly to diet and environmental conditions. But the genetics of race is an inexact science. And since many people have ancestors from different continents — making them a genetic admixture — the data are rarely clean-cut. In other words, ethnicity is relevant to nutritional genomics, but only as a starting point. Which is why the idea of sorting ourselves by race and pursuing a diet consistent with the original continental diet isn’t going to be very helpful. And why, in fact, the customized diets of most people’s perfect genomic future will probably not be all that different from one another.
Kaput estimates that the middle 60 percent of the bell curve are probably not going to need to deviate too much from the basic fruit-and-vegetable-heavy diet recommended by the Department of Agriculture. The folks who will benefit from customized nutritional packets, he says, will be the 20 percent at either end: those at the top who don’t have to worry much about what they eat — and will thus be able to cut corners — and the 20 percent on the bottom, who respond disastrously to conventional diets and will discover that they need to follow special diets or eat specific supplements. The problem for everyone will be figuring out where they fall on the curve of each disease profile.
Just how far in the future are we projecting here? When will nutrigenomics be ready for public consumption? Even many of those who have faith in the science concede that the staggering complexity of interactions among genes, and between genes and the environment, will be a real challenge to solve. As a workable concept, ”eat right for your genotype” may be a decade or two — or more — down the road.
”Right now, no one in their right mind would offer genetic testing or tell you what drug to take,” says Dr. Muin Khoury, director of the Office of Genomics and Disease Prevention at the Centers for Disease Control. Despite that warning, a handful of companies are already offering genomics profiles and nutritional supplements to early adopters looking for an edge. One company, the North Carolina-based Great Smokies Diagnostic Laboratory, offers a genetics-testing service called Genovations. Clients pay up to $1,500 for a preventive health profile.
For nutrigenomics to realize its potential, though, vast, ethnically diverse databases of genomic profiles will have to be assembled, from which researchers will try to divine patterns.
But that, of course, opens up a whole new can of genetically modified worms. Once our genotypes are in databanks, can we really be sure they won’t be sold to employers or insurance companies? And in what social gulag will those poor saps find themselves who simply cannot resist tucking into a double-cheese all-beef sub during the seventh-inning stretch?
Bruce Grierson is a writer in Vancouver. His last article for the magazine was a profile of J. J. Goldstein, a teenage spelling champion.
Posted on October 1st, 2002dna4wellnessNo comments
By ANDREW POLLACK Published: Tuesday, October 1, 2002, NY Times
Some people can eat slabs of steak and butter without gaining weight or raising their cholesterol levels. Others assiduously shun fats and still have a high risk of heart disease. The different response to diet is determined in part by one’s genes.
Now scientists are beginning to apply genetics to diet, a new field known as nutritional genomics, or nutrigenomics. In the near term, the study is expected to reveal how particular diet ingredients affect health. The ultimate goal will be to tailor one’s diet to genetic makeup.
Mass market products like corn flakes may one day come in different varieties, geared to different subsets of people based on their genes. And dietary guidelines issued by the government or medical societies will have to make more distinctions based on genetic profiles.
”We’re moving into an era where the one-size-fits-all public health strategy for disease prevention will not apply as it currently does,” said Dr. Muin J. Khoury, director of the Office of Genomics and Disease Prevention at the Centers for Disease Control and Prevention.
Pharmaceutical companies are working on a related field known as pharmacogenomics, with the goal of developing so-called personalized medicine. It is known that people with certain genetic variations will not receive benefit from certain painkillers or will suffer serious side effects from a dose of a cancer drug that helps others.
Nutrigenomics would expand the idea of personalized care into the consumer world. ”This will take the benefit of the Human Genome Project and extend it from the hospital to the home,” said Dr. Raymond L. Rodriguez, a professor of molecular and cellular biology at the University of California at Davis.
Already there are some examples. People with phenylketonuria, a rare inherited disease that leads to mental retardation, can avert problems with a special diet low in proteins. People with a particular gene variant cannot digest milk.
The advent of consumer genetics is also raising concerns. Already some small companies are offering vitamins or dietary advice customized to people based on genetic tests. Customers swab the inside of their cheeks with cotton to obtain their DNA.
But many experts say not enough is known yet to support the claims of these companies. ”I’m really skeptical that this is going to lead to health benefits at the stage of knowledge we’re in,” said Dr. Ronald M. Krauss, a senior scientist at the Lawrence Berkeley National Laboratory who was the chairman of the dietary guidelines committee of the American Heart Association.
The companies defend their tests. ”This is not voodoo; this is science,” said John R. DePhillipo, chief executive of GeneLink, of Margate, N.J., which is developing customized vitamins and skin products based on gene tests. NuGenix, a company owned by Mr. DePhillipo’s children, recently began selling customized vitamins at $300 for the test and a one-month supply.
GeneLink does not make public which genes it tests for, but one of them is manganese superoxide dismutase, which is involved in reducing so-called oxidative stress. A variant of the gene that is not as efficient as other forms has been shown to raise the risk of breast cancer, Parkinson’s disease and other diseases, said Dr. Robert P. Ricciardi, a professor of microbiology at the University of Pennsylvania and a founder of GeneLink.
People with this variant would be given vitamins with an extra dose of antioxidants. ”It’s giving some sort of rational approach to nutrients and formulations,” said Dr. Ricciardi. ”A lot of people are just mega-dosing on stuff.”
Sciona, a British company, is selling customized dietary advice for about $200. The company tests for 19 variations in nine genes. Six genes are involved in removing toxins from the bodies. Consumers who have variations that the company says slow this process are advised, for instance, to avoid well-done red meats, which have higher levels of certain toxins.
Another test is for the gene that produces Mthfr, an enzyme involved in using folic acid, an important vitamin. People with a less efficient version of this gene are told to eat more liver, broccoli and other foods rich in the vitamin.
Outside experts acknowledge that scientific papers link certain diseases to genetic variations and diet. But they say dozens or hundreds of genes may be involved. In some cases, data on genetic variations can be conflicting. In addition, they say, the companies have not proved that the diet or vitamins they recommend will really make a difference. For instance, Dr. Khoury of the C.D.C. said, it is not clear that people with the Mthfr variant need more folic acid than they are already getting.
”There is so much uncertainty about the meaning of these genetic tests,” he said. ”Right now we are telling people to exercise, eat well, eat a diet high in fiber, low in fat. From what I see, so far there is no added clinical benefit from the genetic tests.”
Dr. Helen Wallace, deputy director of GeneWatch U.K., a group that led opposition to Sciona’s test, said the advice was too generalized to be worth paying for. ”Most of us could probably do with eating more broccoli,” she said.
Dr. Chris Martin, Sciona’s chief executive, said that although some of the advice was common sense, people took it ”much more seriously” because it was personalized. He said the company had sold more than 600 tests so far.
Genetic tests that are offered as services, in contrast to those offered as testing kits, are not stringently regulated by the Food and Drug Administration. Companies do not have to prove claims, for example, that a particular genetic variation is linked to a higher risk of disease or the inability to use a vitamin. And dietary supplements and cosmetics are also lightly regulated.
Another concern is that some genes that may be tested for dietary purposes are risk factors for serious diseases. Should consumers be told, and do they risk being denied insurance or jobs if that information leaks out? Do they need medical advice? Sciona initially sold its advice through retail stores, but after controversy arose, it is now selling only through doctors and dietitians.
People with a version of a gene called APOE, for instance, tend to have their cholesterol go up or down more rapidly in response to dietary changes, Dr. Krauss said. But this same gene variant, known as APOE4, also means a higher risk of Alzheimer’s disease. ”We don’t even like to measure APOE anymore because it would get people worried about Alzheimer’s,” he said. In some cases, he and others said, it is not necessary to test genes. Other tests, like those for cholesterol, can help guide diet decisions.
Still, despite skepticism about some early applications, interest is growing. Several companies, some still operating in their founders’ living rooms, have sprung up: Galileo Laboratories in Santa Clara, Calif.; Alphagenics of Gaithersburg, Md.; NutraGenomics of Chicago; and NuDisCo of St. Louis.
But much of the early focus is not on customizing foods but on using genomics to unravel the mechanisms by which certain food ingredients affect the body. ”We’d like to know the molecular mechanism of nutrients,” said Dr. Young S. Kim, a program director at the National Cancer Institute, which recently held a workshop on nutritional genomics and cancer prevention.
Scientists at Johns Hopkins have found which genes are turned on by sulforaphane, a compound in broccoli that helps prevent cancer. Dr. Len Augenlicht, professor of medicine and cell biology at the Albert Einstein Cancer Center in the Bronx, found that different genes were turned on and off in mice when they ate the rodent equivalent of an unhealthy Western diet than when they ate a healthy diet.
Dr. Jose M. Ordovas, director of nutrition and genomics at the Agriculture Department’s Human Nutrition Research Center at Tufts, said dietary guidelines would soon have to be customized. ”There are some people at very high risk of cardiovascular disease who, if they follow the current recommendations, they make it even worse,” he said.
Moderate alcohol consumption, he said, is considered to reduce risk of heart disease. But for people with the Alzheimers-linked APOE4 gene, alcohol consumption raises the level of bad cholesterol. People with a certain variant of a gene called APOA1 should eat more polyunsaturated fats than called for in the guidelines.
Nutrigenomics could raise questions about policies to fortify foods. If it is found that only a subset of the population benefits from fortified foods, ”do you give a whole population a higher exposure than normal to a nutrient, without knowing what the risk is?” asked Dr. Patrick J. Stover, the director of the Cornell Institute for Nutritional Genomics.
The research of Jose Ordovas is driven by a simple observation: Only some of us take prescription drugs; everyone eats.
Research in “pharmacogenomics” has shown that the reason the same drug helps some patients, has no effect on others and kills an unlucky few reflects not blind chance but individual genetic differences.
Variations in cytochrome P450 genes, for instance, determine whether or not you make the enzyme that breaks down selective serotonin reuptake inhibitors, also know as SSRIs, like Prozac and dozens of other drugs, and so whether a standard dose will harm you. Tiny variations in the beta 2AR gene determine how asthma patients respond to albuterol. And Genaissance Pharmaceuticals of New Haven, Conn., recently discovered 29 genetic variations that affect how you respond to cholesterol-busting statins.
If DNA variations shape how we respond to drugs, reasoned Dr. Ordovas, director of nutrition and genomics at USDA’s Human Nutrition Research Center, Tufts University, Boston, shouldn’t they affect how we respond to food?
Circumstantial evidence says so. One person goes on a low-fat/low-cholesterol diet and sees levels of LDL, or “bad cholesterol,” plunge. Another substitutes trout for T-bone until he swims and still doesn’t see his cholesterol budge. One person can live on marbled beef and butter with no ill effects. Another gets a coronary.
This month, researchers led by biochemist James Ntambi of the University of Wisconsin in Madison report that mice lacking a gene called SCD-1 can eat all the rich, fatty foods they want and never become obese or diabetic. Humans have SCD-1 equivalents, raising the intriguing possibility that absence of these genes explains the lucky few who reach the age of 90 despite living on Big Macs.
The study of how food interacts with genes is called nutrigenomics. Although barely out of the starting gate, it is already explaining some puzzles. For instance, a gene called Apo E comes in three common varieties, or alleles. Apo E4 is associated with a higher risk of cardiovascular disease. But if an Apo E4 person eats a heart-healthy diet (fewer than 30% of calories from fat, fewer than 300 mg of cholesterol a day), he gets much more benefit than do other genotypes, and so faces virtually no increased risk of heart disease despite the “bad” gene.
“Environment is the leverage you have over your genes,” says geneticist Frederic Abramson. “What you can change most easily in your environment is what you eat.”
Only when an Apo E4 person meets a high-fat diet does trouble brew. His lipid and cholesterol levels soar, much more than Apo E2s or 3s do on an identical diet. Those lucky slobs can pack in buttered muffins with near impunity. But things even out: The lipid and cholesterol levels of Apo E2s and 3s respond less to a heart-healthy diet. And if you have mutations in the Apo A4 gene, those levels don’t respond at all to a healthy diet. All that broccoli for nothing.
A drink or two a day also seems to reduce the risk of heart disease, but this one-size-fits-all advice is genomically naive, too. Alcohol dials down cholesterol levels in Apo E2s, but increases it in Apo E4s. Similarly, exercise increases HDL, or “good cholesterol,” in Apo E4s, but has little effect on HDL in 2s and 3s. Still choking on oat bran? It can lower serum cholesterol only in Apo E3s, notes Artemis Simopoulos, president of the Center for Genetics, Nutrition, and Health in Washington. The rest of us needn’t bother.
Also genomically naive is the advice to limit sodium. Only 15% of the population has sodium-sensitive hypertension; for everyone else, cutting sodium has almost no effect on high blood pressure, says Gerald Combs, director of the USDA’s Human Nutrition Research Center in Grand Forks, N.D.
A final example. Women are told to load up on calcium for bone health. But the gene for the Vitamin D receptor has multiple alleles. “Some of the forms this receptor takes don’t respond as well to increased calcium,” says Dr. Simopoulos. With nutrigenomics, she says, “we’ll be able to target dietary advice based on your genome, rather than make general rules that fail for so many people.”
Dr. Abramson founded AlphaGenics in 1999 on that premise. For about $1,000, the Washington, D.C., company plans to offer genetic profiles, based on about 300 genes that predict how an individual will respond to a particular diet.
Standard medical testing is a long way off. But if a pilot test goes well this fall, AlphaGenics hopes to tell you whether choosing oatmeal over sausage will actually make a difference to your health.
An apple a day may be replaced by obscure molecular compounds and amino acids to stave off disease, thanks to a new focus of genetic research: nutrigenomics.
Nutrigenomics looks at the effect of nutrition on a molecular, genetic level. Forget the RDA (recommended daily allowance), those general guidelines designed for the entire population. New genetic research will ultimately provide diets tailored to your genetic make-up.
Science has long pondered the relationship between diet and metabolism. Why can some people have high-fat diets yet not develop heart disease? Why do some people on moderate-fat diets develop high cholesterol?
Now, following the work of the human genome project, scientists are equipped with the tools to answer these questions, and the results will have fundamental implications for health.
In fact, the field is so promising that Rutgers University has established an assistant professorship of nutrigenomics. Dr. Mohammed Rafi is currently setting up a laboratory and research team that will look into diet and cancer.
That is a long-term project, but some results from the field will be exploited in the near future.
“I believe in five years a simple blood test will determine an individual’s susceptibility to cardiovascular disease,” said consultant Nancy Fogg-Johnson, of the Life Sciences Alliance, who, with colleague Alex Meroli, coined the term nutrigenomics.
Palm-sized devices already exist to analyze DNA, which could be used to detect an individual’s susceptibility to cardiovascular disease.
More importantly, nutrigenomics will allow this information to be matched up against food, and food components, that have a positive impact on health for that individual, Fogg-Johnson said.
The idea is that negative foods, such as saturated fats, could be replaced by positive ones that promote cholesterol breakdown. Eating oat bran instead of a Philly cheese steak, for example.
That conclusion doesn’t take millions of dollars to figure out, but dietary science is still in the dark about how food reacts with the body on a molecular level. Nutrigenomics will turn on the floodlights.
While diets and DNA will initially be matched up in a broad fashion, genetics will play an increasingly precise role in preventative health care.
It will probably take a lifetime, but Fogg-Johnson says that eventually nutrigenomics will be able to discover diets that prevent or retard the onset of the most serious and widespread of today’s killer diseases, like cancer, as well as degenerative diseases like Alzheimer’s.
Nutrition tailored both to an individual’s genetic make-up and their occupation can also be envisaged, where the diet for, say, an athlete takes into account his or her genetic disposition to maximize its effectiveness.
Strides have already been made in commercializing the potential of nutrigenomic research. One company, Galileo Laboratories, is currently in discussion with food manufacturers to bring their products to market.
Galileo specializes in redox failure, a malfunction in vital cellular energy metabolism which causes illnesses like stroke, heart attack, inflammation and diabetes. The company said it has come up with several compounds that could prevent or retard the onset of these diseases.
“Galileo is basically translating (nutrition research) into more product-based approaches and creating products that prevent (or retard) cardiovascular disease,” said Dr. Sekhar Boddupalli, vice president of discovery at Galileo.
Boddupalli also said that nutrigenomics will play an important role in food safety, offering the ability to test the effects of new food components.
“Take trans-fatty acid in food products: 10 or 15 years ago food companies said transfatty acids were not an issue and it has no negative impact on health and wellness,” he said. “Now (the risks are) very clear, and the American Heart Association has come up with a paper that transfatty acids should be labeled on food products, because they increase the risk of arterial thickening. Genomics is a powerful technique to understand if there is an impact of these products on human health and wellness.”
Ultimately, nutrigenomics is just one of a series of genetic specializations, like proteomics and pharmacogenomics, that have followed the mapping of the human genome. But the interaction of food and gene expression will have a much more profound effect on society: Everybody has to eat.
It’s an extremely complex subject, however, and serious issues still need to be resolved.
Insurance will be one of them. Will there be implications for your insurance if you have a susceptibility to heart disease? Will there be implications if you fail to follow a diet to retard the onset of symptoms?
These issues, still uncertain, will undoubtedly get their day in court. Far more certain is that, in the future, your diet will owe more to your genetic soup than to Campbell’s, and the apples you need will come in the form of an amino acid.
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