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FEATURE
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Nurture Your Nature
For Jose Ordovas, good health is not
only a matter of what you eat
by Laura Ferguson
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.
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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.” |
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