Diet and Genetics, Diet and DNA Interaction

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Diet and Genetics, Diet and DNA Interaction


Diet and Genes
It isn't just what you eat that can kill you, and it isn't just your DNA that can save you?it's how they interact


By Anne Underwood and Jerry Adler
Newsweek
Jan. 17 issue - Jose Ordovas has glimpsed the future of medicine, and there's good news for anyone who has just paid $4 for a pint of pomegranate juice. Ordovas, director of the Nutrition and Genomics Laboratory at Tufts University, believes the era of sweeping dietary recommendations for the whole population?also sometimes known as fads?may be coming to an end. Red wine may be better for your arteries than ice cream, but you can't create a diet that's optimal for everyone, Ordovas says?or, to put it another way, even Frenchmen get heart attacks sometimes. Within a decade, though, doctors will be able to take genetic profiles of their patients, identify specific diseases for which they are at risk and create customized nutrition plans accordingly. Some people will be advised to eat broccoli, while others will be told to eat ... even more broccoli.

Maybe you have to be a nutritionist to appreciate the beauty of that scheme. The promise of nutritional genomics?a field that barely existed five years ago?is not to overturn a century's worth of dietary advice but to understand on the most basic level how health is determined by the interplay of nutrients and genes. The old paradigm was of a one-way process, in which "bad" foods gave you heart disease or cancer unless "good" genes intervened to protect you. New research suggests a continual interaction, in which certain foods enhance the action of protective (or harmful) genes, while others tend to suppress them. This supports what we know from observation, that some individuals are better adapted than others to survive a morning commute past a dozen doughnut shops. Pima Indians in the Southwest get type 2 diabetes at eight times the rate of white Americans. Individuals have widely varying responses to high- or low-fat diets, wine, salt, even exercise. Overwhelmingly, though, researchers expect that conventional dietary wisdom will hold for most people. So keep that vegetable steamer handy.

The model for nutritional genomics is the work that has already been done on drug-gene interactions. Researchers are starting to unravel the mystery of why a drug may be a lifesaver for one person while causing a fatal reaction in another, and in a third has no effect at all. Why do a third of patients fail to respond to the antidepressants known as SSRIs, including Prozac, Paxil and Zoloft? The drugs are meant to increase levels of the neurotransmitter serotonin by blocking its "reuptake," or clearance from the brain. Obviously, they can work only if serotonin is being produced in the first place. Last month researchers at Duke University discovered that some people have a variant gene which reduces the production of serotonin by 80 percent?making them both susceptible to major depression and resistant to treatment with SSRIs.

Vegetables and Genes

. Green Tea
. Broccoli

. Soybeans
. Turmeric



Green tea helps silence genes that fuel breast cancer in some women. one example:
Name of gene: HER-2
Function of gene: Triggers growth signals in cells
Long-term effect: Slows HER-2 signaling in aggressive breast tumors


But food interactions are usually far more complicated. "Normally, you take one drug at a time and for a limited amount of time," says Dr. Muin Khoury, director of the Office of Genomics and Disease Prevention at the Centers for Disease Control and Prevention. "If you have a certain genetic variant, you stay away from a particular drug or take a different dose." But nutrients come in bulk, you consume them for a lifetime and you can get them without a prescription, even the Trucker's Pancake Special. Metabolism involves huge numbers of genes interacting in uncountable ways. There are at least 150 gene variants that can give rise to type 2 diabetes, 300 or more that are associated with obesity. Ordovas at Tufts compares the situation to an electrical panel: "We know about certain switches and how to turn them on and off. But in some people, you turn the switch but the light doesn't come on, because there are other switches upstream and downstream that we don't know about yet." It will be years before researchers have a good diagram of the circuit. That hasn't prevented the growth of a fledgling industry in personalized nutritional supplements to treat everything from osteoporosis to obsessive-compulsive disorder. At least one company will even profile your genes to take the guesswork out of choosing makeup.



But pieces of the diagram are beginning to emerge. Green tea contains potent antioxidants known to help prevent heart disease and certain cancers, but only some women seem to show a reduction in breast cancer from drinking it. A study at the University of Southern California suggests that part of the reason lies in a gene that produces an enzyme called COMT that inactivates the cancer-suppressing compounds; women with the gene variant that produces a less active form of COMT showed the most benefit from tea.


One interaction that has been studied in detail involves two categories of enzymes known as phase 1 and phase 2. These work in sequence to eliminate certain toxins from the body, such as heterocyclic amines?potent carcinogens that form, infuriatingly, in the tasty crust on broiled meat. Actually, the amines are not inherently harmful; they are dangerous only after the phase 1 enzymes have begun metabolizing them, and before the phase 2s can finish the job. So, obviously, it is desirable to have a balance of the two enzymes. But some people have a variant gene that speeds up the phase 1 enzymes, so they form carcinogens faster than the phase 2s can get rid of them. This gene is found in 28 percent of white Americans, but roughly 40 percent of African-Americans and Hispanics and nearly 70 percent of Japanese-Americans (who, as it happens, have a high rate of stomach cancer). But there are ways to tweak the system: garlic contains nutrients that slow down the phase 1 enzymes, and a substance known as sulforaphane boosts levels of the phase 2s. And sulforaphane is easy to obtain. You get it from broccoli.