TAKE YOUR VEGGIES

What should you really be eating? The answer lies in your genes.

By Pat Bailey

There’s a new wind blowing from the halls of science down the aisles of your grocery store.

Gone are the days when an apple a day would keep the doctor away and a muscle-flexing sailor drew superhuman strength from a simple can of spinach.

Gone, too, are the days when nutritionists were hell-bent on scaring us away from eggs, sugar and anything halfway tasty. Instead, today’s food experts are peering not just into our pantries but also into our genetic closets, hoping to tell us what we really ought to be eating and avoiding.

Welcome to the age of “functional foods”—the notion that food and drink are far more than just body fuel with a smattering of vitamins. That foods actually may be the purveyors of good health and therefore worthy of the same respect and concern currently accorded therapeutic drugs.

A functional food is any food or food ingredient that provides health benefits beyond the traditional nutrients and calories it contains. It may be a naturally healthy fruit or vegetable or a food that has been supplemented with nutrients during processing or nutritionally enhanced through biotechnology.

Kind of takes the fun out of the dinner table? Perhaps, but the good news is that, depending on our genetic makeup, we now have permission to partake—in moderation—of such former indulgences as chocolate and even red wine.

What other foods qualify as functional? Nutritionist Clare Hasler, a nationally recognized authority on functional foods and executive director of UC Davis’ Robert Mondavi Institute for Wine and Food Science, points to low-fat milk products, fatty fish, whole grains, nuts, processed tomato products, soy, leafy green vegetables and bananas.

Eating such healthful cuisine is more than a fun fad, she stressed; for some people it may be literally a matter of life and death.

“For example, we know that, globally, 30–40 percent of cancers are preventable by diet,” Hasler said. “We think that with certain cancers—colon cancer is one—70 percent of the cases can be prevented by diet and lifestyle.”

Statistics like that have swept functional foods into mainstream public health. In fact, many physicians are now making nutritional prescriptions for such foods as those high in Omega 3 fatty acids, which help protect against heart disease, said geneticist Ray Rodriguez, director of the Center for Excellence in Nutritional Genomics at UC Davis.

“But there’s still one more missing link to functional foods—the molecular basis,” he said. “For many years we’ve understood that certain things may be good for us; now we’re learning why. We’re discovering that a lot of the nutrients in foods become cofactors or metabolites that turn genes on or off as they react with cellular receptors in body cells.”

It’s here in the science of nutrigenomics—where the biochemistry of food intersects the genetic makeup of the consumer—that many researchers see promise.

Nutrigenomics

“I like to say that people bring two things to the dinner table: their appetite and their genotype,” Rodriguez said. “That means that, depending on our genetic makeup, each of us responds a little differently to the same foods.

“This isn’t about good genes and bad genes—just slight variations that were beneficial when we or our ancestors ate a different diet, but that now come into conflict with our cultural eating habits,” he said. “If your genetic makeup and what you eat are slightly out of sync, in time it will lead to disease. We tend to eat ourselves into health or disease over many years.”

He notes that there are 3 million to 6 million tiny genetic differences between people—some of which manifest themselves in health problems.

We have long seen the signs. We’ve known, for example, that 98 percent of Southeast Asians can’t tolerate the sugar lactose in milk. And epidemiological studies have found that an unusually high number—50 percent—of Pima Indians develop adult-onset diabetes, compared with just 7 percent of Caucasians, he noted.

“That tells you that some people’s genotypes —their genetic makeups—are creating problems over time,” he said.

Now the human genome project, a massive effort to identify and catalog all human genes, has made it possible to link such epidemiological patterns with the genes that create them.

“Before, we could only guess at which genetic differences between people contribute to disease, but now we can see them,” Rodriguez said.

Scientists around the world have moved into high gear, mining this information for application in a variety of fields, including nutrition. At UC Davis’ nutrigenomics center, one of only a handful in the nation, 35 scientists from biology, medicine and the number-crunching field of bioinformatics have teamed up to “crack the code of chronic disease,” Rodriguez said.

Deciding how to grapple with massive amounts of data and which health problems to tackle first is a challenge for the researchers. But for UC Davis food scientist Bruce German, it’s obvious that milk should be the first priority in developing a genomics-based strategy for foods and health.

The Milk Genome?

“To me, milk is the low-hanging fruit of the genome,” he said. Studying the genes that are the basis of milk production and consumption could lead the way in a new approach to nutrition and health.

“Scientifically, from the perspective of essential nutrients, we’re pretty well set. There are no new essential nutrients to be discovered, and the success of discovering those nutrients that were essential for humans should have prepared us scientifically for the next phase of nutrition research—optimal diets for optimal health. But we’re finding that the research models for human health are flawed because they were focused on curing disease, not preventing it. Nutrition cannot, in its future, borrow from the pharmaceutical model, which looks for what’s going wrong and develops drugs to fix it,” he said.

The challenge for nutrition in the 21st century is to take healthy people and make them healthier, and that calls for a new health-based research paradigm, German said. He’s certain that milk provides the ideal model for the new approach: It is full of not just essential nutrients but also myriad biomolecules that support growth and development, protect against toxins and disease causing organisms, and stimulate immunological functions.

For example, there are compounds in human milk called oligosaccharides that are indigestible to human infants. Reason would suggest that such compounds would pass right through the babies—but they don’t. Researcher Bob Ward in German’s lab, working with David Mills in the viticulture and enology department and Carlito Lebrill in the chemistry department, has found that the oligosaccharides are actually feeding important bacteria in the infant’s stomach, apparently promoting the competitive growth of beneficial bacteria while discouraging the growth of harmful bacteria.

And then there’s the protein alpha-lactoalbumin, the most abundant compound in milk and an essential chemical for producing the milk sugar lactose. A “smart molecule,” this protein has been shown by Swedish researchers to be elegantly designed to unfold and become active in the infant’s small intestine, German said.

And there’s more: lactoferrin, a protein found in human milk and tears and also cows’ milk, which carries iron and aids in digestion. Work by UC Davis nutritionist Bo Lonnerdal’s group has shown that when lactoferrin is digested in the intestine it yields peptides capable of killing harmful bacteria.

German is coordinating an international consortium of scientists focusing on the evolution of milk’s distinctive properties, studying the genes that produce them and that affect human consumption of milk. For example, lactose-intolerance is a prime example of a dietary problem rooted in the evolution of people and milk.

“It’s now known that people who can consume milk all their lives are mutants from the mainstream of humans,” German said. “The genetic mutation responsible for maintaining production of the enzyme that breaks down lactose throughout life has been identified, and apparently it arose in populations that maintained animals for their milk as food. To me, this means that the milk of cows and other animals was so valuable to humans as food that there was literally a Darwinian selection pressure to enable life-long consumption. But it also implies that not being able to consume lactose was a disadvantage. Therefore, we think it is important that we learn how, for example, to make dairy products for people who can’t digest lactose.”

Gene Jockeys Are Waiting

As food scientists and nutritionists sort eagerly through the treasure trove of health-promoting compounds hidden in our everyday foods, molecular biologists wait in the wings. Once the nutritionists decide which plants and animals might best be engineered to enhance their nutrient value, the gene-swapping technology will be available to make it happen.

Some, like UC Davis animal scientist Jim Murray, have a head start. Murray and colleagues have cloned a line of goats that produce in their milk unusually high levels of a compound called lysozyme, a powerful protector against viral and bacterial infection. Human milk contains 1,500 times more lysozyme than does regular goats’ milk, but the genetically modified goats give milk with 60 percent to 70 percent of the lysozyme found in human milk.

Given regulatory approval, lysozyme-rich goats’ milk could be on the market in two years, Murray estimates. With adequate research and development funding, enriched cows’ milk could follow in about a decade.

But Murray knows that, currently, the public isn’t receptive to the development of genetically modified food products—especially milk. Consumers may ignore the fact that genetically modified grains are used in a long list of the processed foods they already eat, but they are not ready to wash that food down with a glass of genetically modified milk.

Murray would love to see the technology and the lysozyme-producing goats make their way to Africa, where some 2 million children die annually of viral or bacterial diarrhea. He’s confident that lysozymic milk would better protect children against infection.

Kent Bradford, director of the campus’ Seed Biotechnology Center, also looks to Africa and other developing regions as places where genetically engineered foods might be accepted and have their greatest impact.

“In developing countries we need to essentially provide more nutrients per acre—to make crops that are more nutrient dense,” he said.

What, Then, Should We Eat?

Whether the functional foods of the future are genetically modified or not, it’s imperative that the research community get a handle on the related economic and social issues, said Carl Keen, chair of the UC Davis nutrition department, whose research expertise includes the health benefits of chocolate.

“We need to know what consumers want to eat,” he said. “And we must take into consideration what is economically feasible for the food producer, the processor and the consumer. It’s no good if I say, ‘Here’s the perfect food’—but it costs too much. So this research has to be done in tandem with the behaviorists and the economists.”

Keen for many years has studied the impact of diet on fetal development and gene-nutrients interactions. About seven years ago, he began exploring the possible health effects of chocolate and other cocoa-based products. His lab has since discovered that a group of compounds called flavanols, which occur in chocolate and other plant-derived foods, may reduce the risk of blood clots and may help to protect against cardiovascular disease. Chocolate, he says, depending on how it is made, can be one “vehicle” for delivering these health-promoting compounds to consumers.

He is encouraged that a new campuswide Foods for Health initiative, spearheaded by the College of Agricultural and Environmental Sciences, will draw broadly on expertise from medicine, veterinary medicine, engineering and the biological sciences. And it will tap the strengths of scientists housed on campus at the U.S. Department of Agriculture’s Western Human Nutrition Research Center.

This integrative research effort, he predicts, will culminate in a better understanding of genetic variability among people, in new information about the beneficial compounds in certain foods and in a host of new food products that are either genetically engineered or fortified to contain more of these compounds.

He hopes nutritionists will begin to tell people what foods really are good for them, rather than nagging them about those that aren’t.

In the future, nutrition will become highly individualized, with information and guidance provided by the family physician, as well as by dietitians and pharmacists, predicts food scientist Bruce German. And that, in just a matter of years, will lead to the elimination of allergies, obesity, osteoporosis and diabetes.

“It’s a lot like dentistry,” he said. “It used to be that you waited until you got a bad tooth and then pulled it. Today there is an entire new field of preventive care—you see the dentist every six months, not to cure disease, but to prevent it. Our children’s generation will die with a full set of beautiful teeth. In a few years, we’ll be able to do the same with diet and health.”

Pat Bailey writes about the agricultural, nutritional and veterinary sciences for the campus.