Your Genomic Diet

Your genetic profile could be the key to staying healthy and eating right.

Imagine a diet plan that saw through to the core of your being and beyond, that took into account not just the foibles and little secrets no one else knows about (it’s awfully easy to dispose of incriminating Wendy’s bags and 3 Musketeers wrappers) but even the secrets that you don’t know – secrets that can help keep you alive longer and in better health.

This is the promise – and the threat – of the latest scheme for dramatic health improvement to fall out from the big bang of the Human Genome Project. Nutritional genomics – or nutritional genetics, or nutrigenomics – examines your diet and your genes to determine how they interact. Proponents argue that nutrients in food alter gene expression or structure, acting differently on different people according to their genetic makeup. Once these interactions are understood, the story goes, people can make up for inherited weaknesses or genetic flaws by eating differently and, when necessary, taking dietary supplements. Understanding the links between genes, specific nutrients, and a range of diseases – from diabetes and heart disease to less obvious diseases like some cancers and neurodegenerative syndromes – will result in a diet plan tailored to your very own gene profile.

If genes are destiny, science has been doing its best to alter that destiny, and of course venture capitalists, burned and jaded by high tech, are looking for ways to turn the science into profit. The new field of nutritional genomics is taking off in both the United States and Europe, with geneticists, nutritionists, and informatics specialists collaborating to analyze data from long-term health studies using powerful new genomic techniques. The deliberate pace of careful scientific research isn’t fast enough, though, for baby boomers willing to spend whatever it takes to stave off if not vanquish the depredations of age. So companies are springing up, vying to take a swab from your cheek, test your DNA for a few genetic variants, and tell you that if you don’t follow their guidelines you’re headed for trouble. Given the state of current research, nutritional genomics hasn’t progressed very far beyond standard, sensible dietary advice. But if you’re paying a lot for the advice, it probably means you’ll take it seriously.

I recently filled out a diet survey devised by one of the most ambitious of the new companies and got my score from the director of diet and nutrition. The biggest surprise was that what I eat is not more alarming. Perhaps because I write about food and am a restaurant critic, I eat a very peculiar and imbalanced diet (or perhaps I am simply peculiar and imbalanced, which is common in the food-writer game).

I skipped the company’s genetic workup, which I didn’t have time to take. Or so I said. The reality is that the number of diet-gene interactions that are sufficiently well understood to lead to specific and helpful advice is very small, and the number of relevant genetic variants for which it is practical or feasible to screen is even smaller; whereas a condition like obesity can involve hundreds of genes interacting in complex ways. In addition to these limitations, there are the uncertainty and risk of obtaining any genetic information about yourself. Companies, of course, promise complete confidentiality, but you never know. And the results of genetic screening are almost invariably ambiguous, with few straight paths from individual variant to effective intervention. I found it telling that the academic researchers I asked hadn’t had themselves screened (or bothered to try the experiment I had in mind, of submitting the same swab with two or three completely different diet surveys).

My discussions with several researchers and one dietician did make me think that the field of nutritional genomics has real promise. And I might even start eating more fatty fish – though I fear that like many people told to eat fatty fish, I’m likelier to line the pockets of the dubious dietary-supplement industry. That industry, like all the big food processors, is looking hungrily at every development in nutritional genomics.

A leading research center in the new field is the Center of Excellence for Nutritional Genomics at the University of California, Davis. It owes its prominence to a five-year, multimillion-dollar grant from the National Institutes of Health, and to the efforts and vision of its director, Raymond L. Rodriguez, a cellular and molecular biologist. Rodriguez had been working to reengineer common food plants like rice, enriching them with important nutrients, and became increasingly curious about how human genetic variants enable or hinder metabolism of nutrients.

Like all geneticists, Rodriguez was excited by every step of the decade-long Human Genome Project, and like every shrewd grant applicant, he tried to imagine the next big use for the information it yielded. Its first large and obvious commercial and scientific application was in pharmacogenomics – matching drugs to populations with certain genetic characteristics. Many researchers, Rodriguez among them, realized that they could apply a similar approach to nutrition, matching the effects of nutrients to genetic variants. Many drugs, Rodriguez says, are metabolites engineered to work on specific sites in the body to achieve specific goals. So is food, although food incorporates dozens or hundreds of metabolites, and they are usually very imprecisely engineered by nature. The action of specific nutrients on the body could be correlated with individual genetic profiles to similar useful effect – maybe even to similar profitable effect.

“You bring two things to the table,” says Rodriguez, an affable man of medium height and luxuriant gray hair. “Your appetite and your genotype.” He believes that the public, however buffeted by changing health messages, is ready to alter its diet according to gene type. There has been a “paradigm shift,” he claims, in the public understanding of food, from the conception of it as a means of survival in a hostile environment, to the 20th-century demand for tasty and wholesome food, to the recent fear of food-borne microbes and a search for food free of them. Now people can intuitively grasp that food affects the way genes behave, for good and for ill. “When you consume a food, your genes are like a Christmas tree, red and green lights that flip on and off and flicker back and forth,” says Rodriguez. “My Christmas lights differ from yours and flicker at a different rate. Over time, depending on your types of genes and how frequently they’re turned on and off, you’ll either be healthy or in a disease state.”

In 2001, Rodriguez asked Wasyl Malyj, a colleague at Davis with a background in molecular biology and informatics, if he would be interested in working on nutrition. Malyj began looking for tools but knew there was no such thing as a molecular video camera that can provide continuously refreshed data on how an entire genome responds to diet and environment. Malyj and his colleagues would have to content themselves with the expensive and partial snapshots provided by existing technologies. (One of these is the GeneChip from Santa Clara, CA-based Affymetrix, which can register the presence of particular biomolecules.) And Malyj recognized that algorithms developed at Stanford University in the 1990s could yield information about diet-gene interactions by helping to identify underlying patterns in hundreds of data sets involving thousands of different genes.

“Most investigators,” Rodriguez says, “are under the false impression that one lab can do it all, or collaborate with a few others and computational scientists and crack the code. We wanted to network metabolic databases, genetic databases, and medical records.” Malyj, a bearish man with great enthusiasm for his subject, adds, “We realized early that this would have to be multidisciplinary, and that not many people were doing it.”

Genetic Cookbook
The groundwork for nutritional genomics was laid by researchers like Jose Ordovas, now the director of the Nutrition and Genomics Laboratory at the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University. Ordovas has spent decades studying the correlation between the metabolism of dietary fats and the risk of cardiovascular disease. Perhaps the best-studied diet-gene interaction involves low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol. One of the most interesting findings of recent years concerns HDL and LDL cholesterol and a gene variant, or allele, that regulates their metabolism. Some people who eat a diet high in saturated fat will never see an increase in their “bad” LDL cholesterol, whereas others will see a spike and won’t even benefit from following the universal advice to eat a low-fat diet. It turns out that the differing effects of a high-fat diet depend in part on an allele of a gene involved in the metabolism of “good” HDL cholesterol called the hepatic-lipase gene. Ordovas explains that the remedy for these frustrated dieters is to continue eating a normal amount of fat, but to make a very high percentage of it polyunsaturated.

This kind of targeted advice, which can be dispensed to anyone at the return of a genetic screening, is the great promise of nutritional genomics, and cholesterol is the teasing example that drives businesses and researchers forward. But it is only one needle in a very high haystack. Ordovas was able to identify the curious effect of the hepatic-lipase allele because he had access to data from the Framingham Offspring Study, part of the huge, very well funded, decades-long Framingham Heart Study conducted by NIH’s National Heart, Lung, and Blood Institute.

Walter Willett, a professor of epidemiology and nutrition at the Harvard School of Public Health, conducted a review of the Davis center in his capacity as chairman of its external advisory committee. He told the Davis researchers that new observational studies would be prohibitively expensive to mount, and that the center should devise questionnaires to be incorporated into established long-term health trials and seek to obtain serum or blood samples from subjects to screen for genotype. Already the center has begun several collaborations, one with a long-term asthma trial under way at the University of California, San Francisco, where the researchers will look for connections between diet, genotype, and the disease, and others with studies of prostate cancer and restricted-calorie diets.

The study of diet-gene interactions in heart disease progressed so quickly, not only because that’s where the money was, but because the biomarkers for heart disease, like HDL and LDL cholesterol, are well understood and easy to measure. But the Davis researchers are hoping that the accumulation of genetic information about many populations, combined with the techniques of systems biology and the algorithms Malyj and his colleagues are using, will be able to disclose more-obscure diet-gene interactions.

They have their work cut out for them. Cancer, despite a huge scientific literature and investment in research, illustrates the difficult proposition for nutritional genomics. Markers vary for each kind of cancer, and environmental stimuli might play important roles in the disease’s progress. For cancer, and for cardiovascular and other diseases, the field’s first results are likely to be generalized recommendations for large ethnic groups whose genotypes are relatively well defined and easily studied, and of course for men and women, whose needs for and reactions to nutrients can differ greatly. Despite the number of genetic-screening companies contending to charge hundreds of dollars to devise individual “DNA diets,” the narrowest focus Rodriguez foresees in his lifetime, he says, is at the level of “a middle-aged man of Hispanic descent” like himself. And that, he says, is “close enough.”

Soy Solutions
It is these subpopulations that NIH expects Davis to study. The Davis center’s grant comes from NIH’s National Center for Minority Health and Health Disparities. Already researchers have found that African-American and Mexican women exhibit differences in folate metabolism, which can affect cancer risk and has been implicated in neural-tube defects in newborns. Green leafy vegetables are rich in folates. But if a diet recommendation is to be realistic or helpful, it must take into account what people can afford and whether they can find it. And that’s to say nothing of whether they like eating, say, broccoli (the cure-all, along with its cruciferous cousins cauliflower and cabbage) and soy, which many non-Asians view with dread.

Rodriguez is excited about preliminary results involving soy and prostate cancer, to which African-American men are disproportionately susceptible. In 1997, a researcher at the University of California, Berkeley, Alfredo Galvez, studied the benefits of lunasin, a bioactive isoflavone in soy apparently associated with reduced levels of heart disease and several cancers, including prostate. Lunasin seems to increase the expression of genes that monitor DNA damage and suppress tumor cell proliferation.

These results – like so many that the public and the food industry seize on – are based on cell cultures, not human studies. So Kevin Dawson, senior informatics scientist at the Davis center, initiated a collaboration with the Prostate Cancer Education Council in Colorado, where rates of prostate cancer are high and where data collection is both broad and detailed. The results seem so promising that they should encourage everyone to eat soy protein once a day (unappetizing as that might sound). But Dawson cautions that the picture of prostate cancer he is trying to draw involves many more nutrients, and that the effects of soy in different populations – especially in populations that have not traditionally included soy in their diets – must be studied over the long term.

For now, even Rodriguez is disposed to generalize his diet recommendations. For example, he recently told a man who has sought alternative treatments for his late-stage prostate cancer to eat tomatoes and sauces with tomato paste for their lycopene, which is strongly associated with lowered incidence of prostate cancer, and to try to eat soy, too, in soy milk or edamame.

Anxious yuppies want more sooner, of course, not to mention eternal, aging-free life. Companies offering “DNA diets” promise customized, expensive diets that fit right in with the current idea of personal service as status symbol. It hardly matters, perhaps, that the number of genes such companies are able to test for is minuscule, and that the advice they can give will almost certainly not be a matter of life and death. Their selection of genes is based on published papers, their nutritional guidance usually the latest from the American Heart Association. What matters is that the idea is catching on, in a very small and very health-conscious segment of the population – and that the commonsense advice the companies are likely to give, with the smallest soupçon of genetic-based rationale, is unlikely to do any harm.

Rodriguez does see home testing in the future: “The trend is faster better cheaper, for private, in-home, disposable tests. Pee on a stick and see if I’m at risk for many diseases.” And optimists say that in ten years the number of genes that can be reliably and cheaply tested for will be closer to 1,000 than 20, and that patients will arrive at health providers’ offices carrying their own gene chips, which can be fed into computers.

If the American Dietetic Association has its way, those health providers will be dieticians. Last April, the journal of the 65,000-member group published a review of nutritional genomics that concluded that the “limited number of certified genetic counselors” left the field clear for “dietetics professionals…to play a primary role.” Dieticians as counselors is fine by Rodriguez, who says that doctors want the kind of yes/no, disease/not disease binary conclusions that nutritional genomics can’t yet provide, and that dieticians know something about preparing food, whereas nutritionists concentrate on research. That dieticians know much about preparing food is a debatable point, at least for food writers, but they often do take a concerned interest in your welfare.

Diet Advice
I filled out a diet survey from Sciona, a company whose website promises “professional genetic screening” that allows people to base “their most important health decisions” “not on fashion but on their own personal ‘inside’ story.” For several hundred dollars, a customer receives a report based on a detailed nutritional questionnaire and the results of a cheek swab that tests for 19 genes. I knew that I didn’t have the time for a genetic screening, but I did look forward to shocking a dietician.

Yael Joffe, however, the dietician in charge of designing Sciona’s questionnaires and correlating the results with the swab report, was far too sensible and nice to be shocked. She calmly assessed my diet, which is usually low in meats except when I taste through an entire menu, as I do a few times a month as a restaurant critic, and exceedingly high in sugar, owing to an insatiable sweet tooth.

Sciona tests only 19 genes whose variation can result in specific dietary recommendations, Joffe assured me, so its report is not a general assessment of a customer’s health. Its main areas of concern are heart health, bone health, inflammation, detoxification, and oxidative stress. She took me through each area, explaining the advice she would give me based on my answers and how it might change if I had a specific genetic variant. Unsurprisingly, the advice accorded strongly with common sense. And as someone who holds buying from farmer’s markets to be a God-given mandate, I was heartened to hear her say in every area that the first recommendation would be to increase (or decrease) consumption of a certain real food and only in the event of certain genetic variants to take supplements.

Such advice, of course, is far from a personalized diet based on nutritional genomics. In the same way that personalized medicine has been slow to emerge from pharmacogenomics, it’s likely to be a while before our genetic profiles will tell us exactly what to eat. For starters, nutritional geneticists will need far cheaper and faster genetic-screening tools.

Still, the makers of omega-3 and folic-acid supplements, and of calcium supplements for women, will be very pleased if messages like Sciona’s filter down to the public. My own biggest shock: that because I don’t drink soda, my extreme consumption of sugar doesn’t throw my entire diet out of whack. I’m a bit light on whole grains and the dread omega-3s – which, however, I was pleased to learn can be obtained not only through mackerel and sardines but also through the delightful-sounding flaxseed hot cereal. I’m ready to make Pascal’s wager, as Ray Rodriguez calls the proposition of following dietary advice. (Blaise Pascal, the 17th-century French scientist and philosopher, argued that if erroneously disbelieving in God consigns you to hell, but erroneously believing in God has no consequences, it’s only rational to believe in God.) If flaxseed on the stove in the morning and sardines from the can at lunch are what will help me live healthier and longer, I’ll learn to like them. But I won’t give up sweets.

Corby Kummer is a senior editor at The Atlantic and the author of such books as The Joy of Coffee and The Pleasures of Slow Food.

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