Tufts Magazine logo Tufts seal
The online edition of Tuft's quarterly publication Contents Back Issues Subscribe Contact Us
Selected Features
Professor's Row
Magazine cover photo
Talk to Us
Send a Letter
Send a Classnote
Update your Records
Related Links
Tufts E-News link
Tufts Journal link
Tufts University link
link to Alumni Office
Tufts Career Network link
Support Tufts
Summer 2003
Nurture Your Nature
For Jose Ordovas, good health is not only a matter of what you eat

Illustrations by Bruce Hutchison

Jose Ordovas pauses midsentence to listen to the young woman’s voice on his answering machine; she would like to work with him in his lab at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts ; she urges him to call her back. Ordovas shakes his head with amazement. The call is one of countless he has received since he appeared on CBS News Sunday Morning and talked about nutrigenomics, an intriguing new field that studies how foods and diet interact with genes to promote health. Many callers are researchers, but others are simply people frustrated by ongoing illness as a result of their genetic makeup; they have the misfortune, he says, of “not choosing their parents well.” One caller he remembers well: an Indy 500 race-car driver. “It was funny, how well he understood it,” recalled Ordovas. “He said that what car drivers and engineers want is to have engines that will work with one type of gas so they can simplify and speed up maintenance procedures. But, he said, obviously we cannot do that with humans because that would be cloning—all of us would have to have the same engine, and we don’t want that. What we have to do instead is provide every person with the right fuel so they can run at their optimum performance, so to speak. And that’s so true: we each need to have our own specific fuel. We all don’t run on the same gas.”

For Ordovas, director of the Nutrition and Genomics Laboratory, the race-car metaphor is worth retelling as it clearly expresses both the complex challenge of nutrigenomics as well as its fascinating potential. In the future, uncovering the secrets of genetics, combined with our growing understanding of nutrient metabolism, may help formulate customized “fuels” to prevent or slow disease. The field raises the prospects that, based on genetic tests, personalized diets could keep each of us running at “optimum performance” well into our later years, improving not only our overall health but how gracefully we age.

Does it represent the fountain of youth? Ordovas is quick to answer no. But he and others do predict that our attitudes toward life expectancy and aging could brighten if we adopted the attitude of “Nurture Your Nature.” Rather than complain about (or ignore) the genes Mother Nature gave us at conception, we accept them as a foundation for tailoring healthy diets and lifestyles.

As senior scientist at the HNRCA and professor of nutrition and genetics, Ordovas says heart disease makes a convincing argument for such a positive perspective. For more than 20 years, he has advanced the genetic understanding of cardiovascular health, including exploring some 40 genes for heart disease. He and his colleagues are now investigating another 100 genes associated with factors that affect cardiovascular disease, including genes related to obesity and diabetes. Heart disease, says Ordovas, is a good model for nutrigenomics and nutrigenetics. Rather than offering people general dietary and exercise recommendations, they provide a specific “reality check” for risk and susceptibility and offer customized guidance.

“If you ask the average American about healthy habits, 70 to 80 percent know what they are, but only 20 percent stick to them,” he says. “Where the genetics may help is by providing hard evidence of risk imprinted in each individual’s genome. And as our knowledge increases, it will be possible to reach a high degree of precision of future disease risk, but also a customized set of “tools” to compensate for genetic predisposition.”

New tools are clearly needed. This year an estimated 1.1 million Americans will suffer a heart attack; some 40 percent of those attacks will be fatal. If you combine the seven other causes of death after heart disease—including cancer, diabetes, chronic respiratory disease, pneumonia and accidents—they equal the number of deaths caused by heart disease. A genetic test early in life, and even as young as infancy, would reveal if a person is susceptible to heart disease and how diet and exercise could be personalized to reduce risk, explains Ordovas. “You might be born with a high chance of developing a problem,” he says, “but it doesn’t have to be inevitable.”

For the most part, heart disease could be prevented with common sense, but as we all know, this is the least common of all senses. It is too simple—eat less, exercise more, burn calories. “We know that general recommendations for these kinds of changes don’t work, that the reaction of a young person—the prime candidate for prevention—is that they are not going to worry about it,” says Ordovas. “They are going to live forever! Moreover, the current lifestyle and commercial pressures do not favor healthy cardiovascular behavior. Genetics can give people the right incentive to undergo behavioral changes based on their precise assessment of risk, but also based on the hope provided by the customized diet and exercise choices that favor a long and healthy life.”

A modern lifestyle can raise havoc with “thrifty” genes inherited from leaner times.
Scientists already have proven that different nutrients directly affect the risk for heart disease. Polyunsaturated fats are better for the heart than saturated fat because they can regulate certain genes related to cholesterol. Certain drugs called statins have been developed from genetic research based on discoveries about how “bad cholesterol” or LDL (low-density lipoprotein) cholesterol is regulated in cells.

Many scientists, including researchers at both the Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy at Tufts and the HNRCA, are adding to this growing body of knowledge. They have found, for example, that broccoli, rich in vitamins, high in fiber and low in calories, helps reduce and prevent ailments like cancer, diabetes, osteoporosis and heart disease. Plant pigments, from the blue in blueberries to the green in spinach, provide many health-promoting compounds as well. Tufts researchers also have closely studied the health benefits of vitamin E, credited with boosting immunity, and have urged people to eat more sources of the vitamin, including nuts, seeds, whole-grain breads and leafy green vegetables. Tufts experts have shown how just a few servings of fish each week can be potentially lifesaving by reducing the risk of heart attacks or other heart problems.

But while the right foods clearly have health benefits, scientists interested in nutrigenomics recognize that food is only half of the health equation; genetics, how genes work and regulate cell activity, is an equally critical factor.
There are cases in which genetics by itself plays a very prominent role in determining if an individual will develop a disease. This is true with familial hypercholesterolemia, affecting about 1 in 500 Americans. Subjects affected by this genetic disorder have a dramatic risk of developing early heart disease, and this makes even more important an early detection of the genetic defect in these individuals in order to begin aggressive therapy as soon as possible.
But for most of the population, the genes are only, to varying degrees, “predisposed”; they exist but may never be consequential. The determining factor is how behavior—diet, exercise and many other habits—interact with the genes to trigger, or not, genetic predisposition.

For most of us, that genetic predisposition does not favor the urban, modern lifestyle. We still carry the so-called thrifty genes, pre-set for the hunter-gatherer lifestyle of our ancestors, with high physical activity and consumption of low-fat foods.

But due to urban living and greater prosperity, we now consume an “atherogenic diet”—fatty meats, foods high in starch and sugar, and few fresh fruits and vegetables. Under these conditions, coupled with less physical activity, these thrifty genes are no longer optimal.

“These ‘thrifty genes’ were able to survive under adverse conditions, where food was scarce,” says Ordovas. “But now, the game has changed entirely. The people who were leading the pack are now being left behind by diet and sedentary lifestyle.”

At the same time, Ordovas cautions against making sweeping statements about genetic capabilities. Specific mutations on the genes can have specific influences. Each of us, through our parents, receives what Ordovas describes as “the lottery of genes”; it determines our hair and eye color, among other unique features. This lottery determines, as well, how each of us responds to diet and exercise. While the current global nutritional recommendations might work for a large number of people—low fat, five fruits and vegetables a day—the specificity of our genes also means that they may not work for everybody.

“There are some people at very high risk of cardiovascular disease who, if they follow the current recommendations for a low-fat diet, make it even worse, and we should always keep in mind that it is not only about the ‘quality,’ but also about the ‘quantity.’ Each calorie counts,” says Ordovas.

Or consider studies on alcohol. Moderate alcohol consumption is generally considered to reduce risk of heart disease. But studies have shown that for people with the APOE4 gene, for instance, 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.

A spectrum of risk exists for each of us, based on our genetic map.
People actually have a spectrum of risk, explains Ordovas, beginning with a range of genetic predisposition made up of mutations in their genes. “And then you add the spectrum of environmental and behavioral risk—smoking, obesity, exercise, alcohol, stress. Because of your particular genes, you may be lucky; you may be a “bad” eater, enjoying all the things we’re told are high in fat and calories, and you still have no ill consequences. We all know people like that and probably envy them. But if you have the wrong genes and the wrong environment, you will most likely have disease.”

The study of nutrigenomics is also shaded by complex and subtle influences such as where we live and level of exercise and stress. Predisposition to disease is not an automatic recipe for poor health; we can compensate for mutations because genes behave differently in different environments. For instance, a man who has a gene mutation for familial hypercholesterolemia but who lives in traditional, rural China may live well into his 70s, never suffering from heart disease, says Ordovas. His lifestyle—a low-fat diet, physical activity on a daily basis and low stress—have compensated for its presence.

Ordovas was fascinated by science early on. He grew up in Spain, and by age 13 was working in his school’s chemistry laboratory, helping set up labs and teaching his peers. After receiving his Ph.D. from the University of Zaragoza, he came to study at what is now known as the HNRCA at Tufts focusing on determining factors that promote the well-being of older adults, and one of six USDA human nutrition research centers in the United States. Located on the Tufts health sciences campus in Boston, it houses many researchers who also have faculty appointments at the Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy.

What was supposed to be a one-year research experience evolved into a long-term goal, and he continued investigating the relation between lipid metabolism, nutrition and health, incorporating in the early 1980s a genetic component.
In 1990, the U.S. Department of Energy and the National Institutes of Health announced the U.S. Human Genome Project. The primary goal was to develop a draft sequence of DNA to provide a foundation for obtaining a finished sequence that could be a valuable tool for researchers hunting disease genes. Ever since a draft of the Human Genome Project was published in 2001, genetic research has quickly advanced our understanding of how genes work in relation to human disease.

Looking back, Ordovas says that early work on genetics at that time was perhaps overly optimistic. “We approached the complexity of the genetics of heart disease with a tremendous amount of naïveté,” he recalls. “We thought we were going to discover one gene and one mutation in that gene and that was going to be it. We were going to prevent cardiovascular disease, and with the rest of our time, we could repeat this feat with other diseases. But the reality was very different. Cardiovascular disease is not that simple, and we can say the same for most common diseases.”

Ordovas and colleagues continue to analyze the genetic map, looking specifically for mutations associated with heart disease and obesity. “Our progress will be slow, but we want to provide accurate and meaningful information,” says Ordovas. “We know that it is quite possible that during our lifetime, we will not be able to know every nut and bolt about cardiovascular disease; this would be perfect, but sometimes reaching for perfection gets in the way of accomplishment. What we need is to have enough to benefit people. We want to answer at least 51 percent—maybe this is enough for people, at least a good chunk of the population, to benefit from this new knowledge. Now we are at the level of ten percent. So we have a way to go.”

In addition to research on the Boston campus, he has created a large “virtual lab” around the world, helping support the study of subpopulations and their health in relation to diet. “What really gets me excited is how these scientific ideas have an impact on people all around the world,” he says. “In any one day I communicate with researchers in Australia, Singapore, Korea, Italy, the Netherlands, the United Kingdom. And then I come into the office and have the continuous excitement of people working here. That gives me a lot of joy because you get different kinds of answers and you are always trying to bring everything together.”

Some commercial enterprises have already tried to bring some of those answers to the marketplace. According to the New York Times, among those hoping to cash in on consumer genetics are “small companies offering vitamins or dietary advice customized to people based on genetic tests”; it only requires that customers swab the inside of their cheeks with cotton to obtain their DNA. Consumers can also buy customized vitamins, skin products and diet advice based on gene tests, and a new brand of health club is already marketing exclusive services that offer patrons health and exercise guidance based on the traditional physical exams combined with genetic tests.

But Ordovas cautions consumers, and urges a much longer view. Our knowledge of molecular mechanisms of nutrients, for example, and how they regulate genes is still evolving. And given the wide array of contributing factors to health — economic and social conditions, culture, behavior and attitudes — our approach to good health is still largely shaped by our own attitudes, choices and habits.

In the laboratory, the nutrigenomics challenge is already considerable, given the enormous complexity of our genetic code. The human genome has about 3 billion nucleotides, the sequence of which determines who and how we are. About 40,000 genes code for proteins that perform most life functions; but their individual performance is affected by the more than 10 million genetic mutations interspersed in our genomes, making each one of us unique from many different points of view, including risk of disease and response to environmental factors.

Scientists are well aware, as is a well-educated public, that medical advances often raise ethical and legal questions at the same time that they promise hope. Questions that will come forth with the evolution of nutrogenetics include appropriate use of knowledge—perhaps a patient would rather not know their genetic makeup, for instance, if it correlates with a fatal disease. How will insurance carriers respond to the evidence of a genetic vulnerability, can a patient’s right be protected, and what measures will be taken to ensure consumer safety? All these factors will play out in coming years and further make the nutrogenetics discussion one of greater complexity.

For Ordovas, however, the ideal contribution of nutrogenetics will be, at first, a subtle but important shift in attitudes about health. Dietary recommendations for a general population, for example, allow for wide interpretation and excuses. But providing customized guidelines based on genetic information, says Ordovas, raises the bar of personal responsibility.

“What we are trying to do now is understand who, in any given population, is at higher risk based on genetic makeup,” he says. “With that, we can have more convincing arguments for subjects, because now we are talking about you, an individual. This is your fingerprint and this is what it says. It says that you have a weak link in something that relates to your heart. With that information, maybe you will think twice before saying, ‘Oh, 40 years from now I’ll worry about it.’ Instead, you might say: ‘Wow, it’s in my genes. It’s there. I have to be smart; I have to take it seriously.’”

Western society is increasingly characterized by high rates of heart disease.
Doing nothing comes with a high price. Billions of dollars are spent each year on medication and interventions. Countries with populations characterized by high rates of heart disease—the entire Western society—are profoundly impacted. “The cost is staggering,” says Ordovas. “The benefit of these new sciences to society would be that you have healthier people who spend less on health care, who spend more on leisure, and who can contribute to a much better and productive society.”

And that will not happen, he predicts, without a radical rethinking of nutrition. To illustrate his point, Ordovas calls up another metaphor, this time one of the 1,000-plus PowerPoint lectures that crowd his laptop computer. In the first image, two train tracks run parallel to each other—genetics and nutrition sciences traveling side by side but separately. In the next, a decaying railroad station is blanketed in fog, its neglected tracks deteriorated beyond repair. Finally, the railroad tracks merge into one single track headed for the horizon.

“What genetics and nutrition have done for many years is taking parallel paths, thinking each one of them was going to solve everything,” says Ordovas. “With this approach we are not going to get anywhere fast. The prevailing global increase in heart disease will only continue to get worse. But when the tracks merge, as is starting to happen, then we can move forward and arrive at the desired answer.”