The DNA Diet

You inherited more than your blue eyes, brown hair and long legs from mom and dad—you also got a set of genes that defines everything about you. Are you a morning person? Do you have the energy of a runner (or a couch potato)? Can you eat rich French cuisine and never gain weight? Most of these tendencies are hardwired into your DNA.

Your genetic makeup may also portend more serious risks—for heart disease, diabetes, Alzheimer’s and obesity, among other diseases. The good news is that the way these genes function is not etched in stone. Some can be turned on or off, depending on your lifestyle.

Even more heartening, the scientists who study the connection between our genes and how we live, a field known as nutrigenomics, have adopted a revolutionary model for conducting research that has so quickened the pace of discovery that one day, a routine pediatrician’s visit may include analyzing a child’s genetic map to identify risk factors for disease and, most importantly, prescribing a specific diet, targeted exercise and in some cases tailor-made pharmaceuticals.

“What I hope is that during my lifetime, we will know that you have a gene that can make you obese or prone to diabetes—but it can’t just end with a label,” says José Ordovas, director of the Nutrition and Genomics Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts. “We have found in cases studied so far that with the right dietary or behavioral change, we can cancel that increased risk,” he says. “In my lifetime I want to see us put, perhaps not all, but enough of the pieces together for this to become a practical application and routine approach to therapy.”

Already, platitudes like “an apple a day keeps the doctor away” are giving way to more individualized recommendations for what kinds of work, play and dining we should partake in.

For example, broccoli is known to have chemicals that can help the body defend itself against cancer. But if you are one of the 20 to 50 percent of the population that is missing the gene GSMT1, your body excretes many of these chemicals before they have time to do any good. A 2005 study by the Institute of Food Research in Great Britain found that people who don’t have the gene need to eat extra servings of broccoli to get the benefit.

Whether your all-day coffee habit is good for you may also depend on whether you have the “fast” or “slow” version of the gene that controls how caffeine is broken down in the liver. Research from the University of Toronto found slow metabolizers who drank two to three cups of coffee each day were 36 percent more likely to have suffered a heart attack than single-cup drinkers. And slow metabolizers who consumed four or more cups were 64 percent more likely to have had a heart attack. By contrast, one to three cups seemed to protect those individuals whose genes made them fast metabolizers.

As for consuming fish oils to lower your cholesterol, it turns out that this is beneficial for the vast majority of us, but in those who have a particular version of the APOE gene, which generates the protein that helps remove excess cholesterol from the blood and carry it to the liver for processing, it actually has the opposite effect. According to a recent study at the Berkeley HeartLab in San Francisco, in the roughly 15 percent of people who have the APOE4 gene, fish oil caused the “bad” cholesterol, LDL, to rise by 15.9 percent.

Bigger Is Better

What these new genetic studies are demonstrating is that broad dietary recommendations are not necessarily good for all people—and in some cases might even do harm. More effective diets will only come from understanding an individual’s entire genetic code, or genome, in combination with his or her lifestyle and environment.

Deciphering the influence of particular genes and their external triggers, nutrigenomics researchers have come to realize, can only happen through cooperative studies that involve larger populations as well as a wide breadth and depth of knowledge and expertise. That is why in just the past five years, many of these scientists have abandoned competition for grants or personal credit in favor of cooperating on broad multidimensional studies.

Ordovas has been a primary mover in this dramatic shift from the traditional this-is-my-research mindset to one of collaboration. Two years ago he co-founded the collaborative CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), which engages more than 600 researchers from large universities and research centers worldwide. He has also facilitated the founding or agendas of many other similarly sized nutrigenomics consortia in the United States, Canada, Europe and Australia.

“We realized that if we want to make serious contributions to this field, we cannot continue to do it in isolation,” says Ordovas, a professor at the Friedman School of Nutrition Science and Policy. “Nutrigenomic researchers working on small population samples could do nothing. So now there are consortiums of individual labs and institutions to create the critical mass that was lacking from each of the individual studies.”

The point is that several hundred scientific heads are better than one, and thousands of test subjects more statistically significant than dozens. Further, by agreeing to use a common methodology—from survey questions to analysis standards—the researchers gather more robust data.

“Think about looking at just a small section of a painting—you don’t see the whole picture,” says Jennifer A. Nettleton, chair of CHARGE’s working group on nutrition and an assistant professor in the Division of Epidemiology, Human Genetics and Environmental Sciences at the University of Texas Health Science Center at Houston.

“José and I work closely within CHARGE, and we are now collaborating on projects that include more than 30 cohort studies from various regions of the U.S., northern Europe and the Mediterranean to study interaction between various dietary factors and genetic information. We pool expertise and resources to create common plans to approach a question.”

CHARGE was one of the groups that contributed to two groundbreaking Alzheimer’s  studies completed in April that identified five new genes associated with the degenerative disease; the findings open up new avenues in the search for a cure. The work involved scientists from 44 universities and research institutions and an unprecedented 54,000 study participants.

Both Ordovas and Nettleton see this cooperative research model as one that could benefit not just nutrigenomics but all medical research. Could adopting this approach also quicken the pace of, say, cancer research? Unequivocally yes, says Ordovas. And new alignments among pharmacogenomic researchers, who study how an individual’s genetic makeup affects the body’s response to drugs, have begun to take hold.

“When we were just waking up to the potential of genetics research in the late ’80s, I did a lot of pharmacogenetics,” Ordovas says. “After that there was a dark time in which things started to separate, but now things are starting to merge again because we see the commonalities.”

The surge in nutrigenomics research has catalyzed this, according to many in the field.

“Ten years ago there were just a few passionate ‘hobbyists’. . . This year the Christmas issue of Nature had eight special articles on nutrigenomics,” noted Ben van Ommen, executive director of NuGO, the leviathan European-based nutrigenomics research consortium, in a March 2011 interview with NutraIngredients. “We have switched from a minority to a feature topic in only a few years,” said van Ommen, a close associate of Ordovas.

Harmful Triggers

So how does our environment affect our genes in the short term? Through the ever-changing part of our genome, the epigenome. A series of tiny chemical tags attach to, or detach from, your DNA or proteins in the nucleus and flip genes on or off based on your diet and the pollutants, climate change and stresses your body encounters.

In fact, the way a gene reacts to a change in lifestyle can mean the difference between sickness and health.

“Humans have mutations in their genomes that have been with us for many, many generations,” says Ordovas. “But their effects are evident only now due to the nature of the society and environment we live in.”

To better understand how genomes react when transplanted to new environments, Ordovas is studying Hispanics in Boston to determine why their rate of illness is significantly higher than that of whites. Clinical depression, for example, affects up to 58 percent of elderly Puerto Rican women living in Boston, compared to 22 percent of their white neighbors—a fact Ordovas calls “totally amazing.”

“Each one of our genomes has been interacting with the environment for thousands of years,” he says. “This created an understanding between our genome and the environment. Imagine you take an orchid native to the tropics and move it to Toronto. It is the same if you take a Puerto Rican to Boston,” Ordovas says, pointing to big changes not only in climate, but in living conditions (close-packed, urban housing), work (indoor as opposed to outdoor) and what foods are available and affordable (processed rather than fresh). “The genome is not prepared for the environment. And this is why you have the increased morbidity.”

Many of the genetic markers associated with higher risk for heart disease, obesity and diabetes are more common in Hispanics. Ordovas theorizes that some of these markers might have worked well with a traditional Puerto Rican diet of rice, beans, fish and fruit, but the addition of starches and sugars—and a pattern of snacking common in the mainland U.S.—may overtax these same genes.

“In a place where you have stress due to economics or living conditions, poor diets and lack of physical activity, you trigger a negative genetic response,” Ordovas says. So while 10 percent of the white population in Boston might be at risk for disease because of this same lifestyle, 40 percent of a minority group could be affected, he notes.

Ordovas is also looking at the ancient circadian rhythms observed in all plant and animal life. They affect our daily patterns of waking, sleeping, physical activity and even the rise and fall of our hormone levels over 24-hour periods.

In humans, these rhythms are controlled by about 20,000 cells in the hypothalamus region at the base of our brain, our so-called biological clock. This “master clock” also controls body temperature, hunger, thirst and our moods. While circadian rhythms are innate, the genes in cells throughout our bodies also have their own clocks that can be disrupted by environmental cues, potentially interfering with the body’s hormonal and metabolic systems.

Ordovas recently collaborated on a study of severely obese women that identified the presence of such peripheral circadian clocks in fat cell genes. They tested the activity of these fat cell clocks as well as triglyceride and cholesterol levels at six-hour intervals during a 24-hour period and found clear rising and falling patterns. The research offers a clue to how fat cell metabolism affects obesity and cardiovascular disease.

“Genetic factors alone do not put someone at risk,” Ordovas says. “You need the environmental trigger, and that is what we are trying to understand: the triggers of our genome so we can silence the mutations we all carry that have the risk of disease.”

This article first appeared in the Summer 2011 issue of Tufts Nutrition magazine.

Gail Bambrick can be reached at gail.bambrick@tufts.edu.