How You <em>Nurture</em> Your Health Could Change Your Genetic <em>Nature</em>

What this study suggests is quite provocative enough for now: take good enough care of yourself, and even your genes will get a makeover.
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I have argued that the power of lifestyle -- physical activity, dietary pattern and avoiding that death grip around a cigarette -- constitute the master levers of medical destiny. In response, I have received some push-back on behalf of genes. The counter-arguments to mine are that what we do will not reliably determine what happens to us, because of the potent influence of our genetic inheritance.

There is of course some truth to this rebuttal. But it's a bit like dismissing the value of master-level seamanship because of the risk of stormy seas. We will never control the wind and waves, but give me a well captained ship any day! In the poem "Invictus," the ship of which we are each captain is our soul. In my purview, it is health.

Let us concede that storms may arise -- in our chromosomes and elsewhere -- that we do not, and cannot control. Let us acknowledge that bad things happen, alas, to good people. Let us be clear that bad outcomes do not mean bad behavior. Let us proclaim no tolerance for blaming the victim of bad fate.

But let us also avow that to a substantial and gratifying degree, we are, indeed, masters of our fate -- captains of our health. Let us respect the modern science that shows the nature vs. nurture debate serves up a false choice -- for we can, in fact, nurture nature.

Your genes are not your medical destiny. With relatively uncommon exception, that is the rule established by ground-breaking research published over recent years, and nicely illustrated by a 2008 paper in the Proceedings of the National Academy of Sciences. That rule could, and perhaps should, remake the way you play the game of life.

The illustrative trial was a pilot study of 30 men with early stage prostate cancer who were eligible to be observed carefully for disease progression without undergoing surgery, radiation or chemotherapy. These men were enrolled into a trial called GEMINAL, developed and implemented by my friend, Dr. Dean Ornish, and his colleagues at the University of California, San Francisco.

Dr. Ornish is best known as the ardent proponent of a very low-fat, plant-based diet for heart disease prevention. His Lifestyle Heart Trial, published almost 20 years ago, showed that an intensive lifestyle program -- including a plant-based diet, daily exercise, stress management and more -- could cause the plaques that block coronary arteries to shrink. A follow-up study published in the Journal of the American Medical Association in 1998 showed that this same intervention substantially cut down on the rate of heart attacks. After 16 years of work on this program, Dr. Ornish finally received news this week that Medicare will reimburse for his "heart disease reversal program" as an alternative to bypass surgery. This is a well-deserved, long-in-coming, seminal achievement.

More recently, Dr. Ornish and his colleagues have been focused on the potential for lifestyle interventions to prevent and treat prostate cancer. Prostate cancer is of particular interest for several reasons. First, it is a highly prevalent cancer, among the leading causes of cancer death in men in the United States. Second, although we have tests to screen for prostate cancer, we can't always predict the behavior of the disease once we find it.

Some prostate cancers progress and metastasize throughout the body, to bone in particular. When this occurs, the disease is both devastating, and often lethal. But some tumors of the prostate are indolent; in essence, they just sit there, doing nothing. As many as 80 percent of men in the U.S. who die after age 80 have prostate cancer, but they die with it rather than of it.

The 2008 study took advantage of this indolent variety of prostate cancer to assess the effects of a lifestyle intervention, without the confounding influences of medical or surgical cancer treatments. The men participating in the GEMINAL study received a lifestyle intervention much like that in the earlier Lifestyle Heart Trial: low-fat, whole foods, plant-based nutrition; stress management techniques; moderate exercise; and participation in a psychosocial support group. The study lasted three months.

Many of the usual measures of overall health were tracked in this study: weight, blood pressure, cholesterol levels and so on. They all improved significantly, as one would expect. The PSA, a tumor marker for prostate cancer, improved, but only trivially.

But what makes this study unique -- and groundbreaking -- is that it measured health markers beyond the list of usual suspects. Using advanced laboratory techniques, the investigators measured the effects of the intervention at the level of the genes.

What they found was remarkable. By examining prostate biopsy specimens before and after the three-month intervention, they saw significant changes in gene activity. Roughly 50 genes associated with cancer suppression became more active in generating RNA, and nearly 500 genes associated with cancer progression became less active. The pattern of change observed in gene activity was consistently, and decisively associated with lower risk of cancer development and progression.

We have long known that lifestyle has a powerful influence on health across a wide array of outcomes. It is not news to you that eating well, being active, controlling your weight, managing stress and not smoking, for instance, can influence your fate.

But we have tended to think in terms of "nature versus nurture" -- with lifestyle and genetic influences on health as independent and potentially competing forces. This study, and others like it, ostensibly change the game. They suggest that lifestyle and genetics are not independent after all, but interact. Even our genes are influenced by lifestyle choices. We can, it seems, nurture nature.

To a Preventive Medicine specialist like me, this is of profound importance. Complacency and fatalism are enemies of disease prevention. For many people, the notion that their medical destiny is written in their genes is a disincentive to take matters into their own hands.

The lifestyle intervention in GEMINAL was rather intense, allowing only 10 percent of calories from dietary fat, and requiring more than an hour and a half of exercise and meditation daily. We don't yet know if less intensive lifestyle approaches would influence genes as this program did. And there is only so much certainty that can derive from a pilot study, limited to 30 men with prostate cancer. More research is required to prove what the current body of evidence suggests. But what it suggests is quite provocative enough for now: take good enough care of yourself, and even your genes will get a makeover.

What we have in this study and others like it is nothing less than an indication that the concept of "nature versus nurture" is flawed and obsolete. Genetic influence is not walled off from the world. Epigenetic influences prevail.

Be careful, though; do not be seduced into thinking that by living well, you get a guarantee of good outcomes. There is, alas, no such guarantee. We can trim the sails, but we do not command the wind and waves.

But on the flip side, recognize that healthful behaviors are not a mere attempt to bluff our way through whatever genetic hand we were dealt. They are, it turns out, an opportunity to reshuffle the genetic deck in our favor.

My concluding perspective on that opportunity, and I hope yours as well, is simply this: deal me in!

Dr. David L. Katz;

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