CHANGING LIFESTYLE CHANGES GENE EXPRESSION

Dean Ornish [12.3.08]
Topic:

These findings may capture people's imagination—so often, people think there is not much they can do, what I call genetic nihilism. But even if your mother and your father and your sister and brother and aunts and uncles all died from heart disease, it doesn't mean that you need to. It just means that you are more likely to be genetically predisposed. If you are willing to make big enough changes, there is no reason you need ever develop heart disease, except in relatively rare cases.

DEAN ORNISH is a clinical professor of medicine at UCSF and the founder and president of the non-profit Preventive Medicine and Research Institute in Sausalito. His most recent book is The Spectrum.

Dean Ornish's Edge Bio Page


[12:05 minutes]


CHANGING LIFESTYLE CHANGES GENE EXPRESSION

[DEAN ORNISH:] For the last 30 years or so, I have directed a series of clinical research studies proving that the simple choices that we make in our lives each day can have a powerful impact on our health and our well being, and much more quickly than had once been thought possible, even at a cellular level. Ironically, we have been using very high tech, expensive, state of the art measures to prove how powerful very simple and low tech and often ancient interventions can be.

My scientific research papers cover a wide range, but my training was very conventional. I trained in internal medicine at Harvard Medical School and the Massachusetts General Hospital. I'm a clinical professor at UCSF. But my interests have always been interdisciplinary. A key moment in his my life was when, at the age of 19 and deeply depressed, I decided not to kill myself. I changed my major from biochemistry to humanities, and transferred to the University of Texas at Austin, where I could design my own major, find the best teachers, and take any course that I found interesting. It turned out to be the best training for what I do, because the intersection between so many different, seemingly unrelated areas and finding the common ground is to me intellectually interesting. And having consciously chosen to live, I decided to live as fully as possible and to take risks that I might not otherwise have chosen. Recently, my colleagues and I have conducted research in areas as diverse as the effects of comprehensive lifestyle changes on telomeres, gene expression, coronary heart disease, and prostate cancer.

In terms of heart disease, we were able to show, for the first time, that it could be reversed by changing lifestyle, and these improvements occurred much more quickly than had once been thought possible. Usually within hours, and almost always within days to weeks, your heart can receive more blood flow. As a result, we found over a 90 percent reduction in the frequency of angina or chest pain.

People not only felt better but also, in most cases, they were better in every way we could measure. Their hearts received more blood flow and pumped more normally. The arteries that feed the heart became measurably less clogged in one year and showed even more improvement after five years. Using cardiac positron emission tomography (PET) scans, we found that 99 percent of the patients in our research were able to stop or reverse the progression of heart disease simply by changing lifestyle, without drugs or surgery.

More recently, we conducted the first randomized, controlled clinical trial showing that the progression of early stage prostate cancer may often be stopped or even reserved by making these simple changes in diet and lifestyle. This study was done in collaboration Dr. Peter Carroll, the chair of urology at UCSF, and Dr. William Fair, who was chair of urologic oncology at Memorial Sloan-Kettering Cancer Center at the time (now deceased). What is true of prostate cancer is likely to be true of breast cancer as well. We also found that the progression of diabetes, hypertension, and obesity could often be prevented, improved, or even reversed in most people.

Our prostate study was a randomized control trial of men who had biopsy proven prostate cancer and who have elected not to be treated conventionally for reasons unrelated to our study. What made this interesting from a scientific standpoint is that we could take men who knew they had cancer from biopsies, randomly divide them into two groups, and have a true non-intervention control group so we could determine the effects of comprehensive lifestyle changes alone without being confounded by other treatments. You can't do that with breast cancer because almost everybody gets treated right away, so you don't know if any improvements were due to the lifestyle changes or the chemo or the radiation or the surgery.

After a year we found that PSA levels, a marker for prostate cancer, went up (worsened) in the comparison or control group, but went down significantly (improved) in the experimental group that made the lifestyle changes we recommended. The degree of change in lifestyle was directly correlated with the degree of change in their PSA levels.

We also found that the prostate tumor growth in vitro was inhibited 70 percent in the group that made these changes compared to only nine percent in the group that didn't. The inhibition of the tumor growth was itself a direct function of the degree of change in lifestyle. In other words, the more people changed, the more it directly inhibited the growth of their prostate tumors.

J. Craig Venter has shown that one way you can change your genes is by making new ones. We are finding that another way you can change your gene expression is simply by changing your lifestyle.

In May of this year, we published an article in the Proceedings of the National Academy of Sciences (Craig was the communicating editor). We found that changing lifestyle actually changes gene expression. In only three months, we found that over 500 genes were either up-regulated or down-regulated—in simple terms, turning on genes that prevent many chronic diseases, and turning off genes that cause coronary heart disease, oncogenes that are linked to breast and prostate cancer, genes that promote inflammation and oxidative stress and so on.

These findings may capture people's imagination—so often, people think there is not much they can do, what I call genetic nihilism: "Oh, it's all in my genes, what can I do?" Well, it turns out you can do a lot, more quickly than we had once realized and to a much greater degree than had been thought possible.

Even if your mother and your father and your sister and brother and aunts and uncles all died from heart disease, it doesn't mean that you need to. It just means that you are more likely to be genetically predisposed. If you are willing to make big enough changes, there is no reason you need ever develop heart disease, except in relatively rare cases.

Last week, we published in The Lancet Oncology a study in the same group of patients showing in collaboration with Dr. Carroll and coauthor Dr. Elizabeth Blackburn, who discovered telomerase. She is favored to win a Nobel prize for her pioneering work. Telomerase is an enzyme that repairs and lengthens damaged telomeres.

Telomeres are the ends of our chromosomes that control how long we live. Four years ago, in a study she did with Dr. Elissa Epel, she found that women who were under chronic emotional stress because they were taking care of a chronically ill child had lower telomerase levels and, as a result, shorter telomeres. What was also interesting was that the best predictor of how short their telomeres were was their perception of stress: the more stressed the women felt, the shorter were their telomeres. They published that in the Proceedings of the National Academy of Sciences as well.

I was deeply impressed by that study. Two years ago, the three of us spoke at a conference with the Dalai Lama, and we got into a discussion afterwards. In my experience, most things in biology go both ways. If stress reduces telomerase and makes telomeres shorter, perhaps stress management techniques, exercise, improved nutrition, and social support might increase these?

Well, that's what we found. After just three months, telomerase increased by almost 30 percent and thus telomere lengthening is likely to have occurred as well. In this context, comprehensive lifestyle changes not only work as well as pharmaceutical drugs, but even better, as no drug has yet been shown to increase telomerase or to lengthen telomeres.

I'm not against the use of drugs or surgery—sometimes, they can be lifesaving—but they don't usually have to be the first choice in treating or preventing chronic diseases. One of the overriding themes of my work is finding that lifestyle changes not only work as well as drugs and surgery, but oftentimes even better.

Nowhere is this clearer than in cardiology where I have spent a lot of time doing studies and where, if you take an evidence-based approach, the most common treatments for heart disease like angioplasties and coronary bypass surgery really don't work very well for most people who receive them. Several randomized control trials of angioplasty and stents—the most recent in the New England Journal of Medicine last year—found that angioplasties don't prolong life and don't even prevent heart attacks unless you are in the middle of having one. Approximately 95 percent of people who receive angioplasties are stable and are not in the middle of a heart attack. In fact the new stents may actually increase the risk of a heart attack. Similar data from randomized controlled trials are available for bypass surgery. Yet these findings have not significantly reduced the rate of angioplasties or bypass surgery.

We spent $30 billion last year just in the U.S. on bypass surgery and another $30 billion on angioplasty, almost all of which could be avoided simply by changing lifestyle. Sometimes, people ask, "Why are you doing this radical intervention?" I reply, "Why is it ‘radical' to ask people to walk, mediate, eat vegetables and quit smoking, but ‘conservative' to cut people's chests open?"

Despite the talk about the need for evidence-based medicine, all-too-often the reality is reimbursement-based medicine. We doctors tend to do what we get paid to do and we get trained to do what we get paid to do. Therefore, I realized that good science is important but not usually sufficient; we needed to change reimbursement as well.

Beginning in 1993, my colleagues and I at the non-profit Preventive Medicine Research Institute began training hospitals and clinics throughout the country in our program of comprehensive lifestyle changes. Mutual of Omaha was the first major insurance company to cover this program; over time, more than 40 insurance companies provided at least some reimbursement. After 14 years and three demonstration projects, Medicare is now covering our program as well. This was a major breakthrough, as other insurance companies tend to follow Medicare's lead. By changing reimbursement, we may help to change both medical practice and medical education.

In 1995, I had a conversation with the Administrator (director) of Medicare at the time. In that meeting, he said, "Dean, before I'll consider doing a Medicare demonstration project, you first need to get a letter from the director of the National Heart, Lung, and Blood Institute of the National Institutes of Health stating that your program is safe."

"You mean that it's safe as an alternative to bypass surgery or angioplasty?"

"No, just that it's safe."

I was incredulous. "You want me to get a letter saying that it's safe for older Americans to walk, meditate, quit smoking, and eat fruits and vegetables?"

"That's right."

So we did. I met with the director of the National Heart, Lung, and Blood Institute at the time, and his colleagues, and we reviewed the medical literature. Not surprisingly, we found that these are not high-risk activities—especially when compared with having your chest sawed open for a bypass operation. In our earlier research, we found that the older patients improved as much as the younger ones, whereas the risks of bypass surgery and angioplasty increase in older patients. So, our program was especially beneficial for older patients in the Medicare population. When you're doing something that doesn't fit the conventional wisdom, it's often held to a different standard.

These approaches are not only medically effective, they are also cost effective. A major study came out in The Lancet three years ago called the Interheart Study. They looked at 30,000 men and women in all six continents and found that almost 95 percent of heart disease is completely preventable knowing what we know today just by changing lifestyles. Heart and blood vessel diseases still kill more people in this country and in most others worldwide than virtually everything else combined. Yet it is almost completely preventable—or even reversible—just by changing what we eat and how we live.

We have 47 million Americans who don't have health insurance in this country, which is really disease insurance. If we are going to say that we want to make healthcare available to everybody and rely primarily on drugs and surgery, as we now do, then costs will go up exponentially, which we can't afford. Then, we have painful choices. Do we ration? Do we raise taxes? Do we let the deficit go up? None of these choices are very good.

But if we can treat the underlying cause of a problem rather than just literally or figuratively bypassing it, your body has a remarkable capacity to begin healing itself. That is as true on a health policy level as it is on an individual level.

Beginning in 1993, we conducted a demonstration project with a large insurance company where they found they saved almost $30,000 per patient in the first year because most of the patients who were told they needed a bypass or angioplasty were able to avoid it simply by changing their lifestyle. Eight years ago, we conducted another demonstration project with a major health insurer, and they found that their overall health care costs for these patients decreased by 50 percent in the first year and by an additional 20-30 percent in years two and three.

Three years ago, the CEO of one company approached me and said that his corporation was spending 120 percent of their net revenues on health care for their employees, clearly not sustainable. They had tried a managed care approach, which is another kind of bypass by treating the symptoms of cost rather the more fundamental causes of why people get sick. Not surprisingly, that didn't reduce costs and it led to a contentious strike that cost the company a billion dollars.

I said, why don't we try an approach that is based on treating the causes of why people get sick and incentivize healthy behaviors? They did that, and within a year the costs came down 11 percent and they have remained flat since then. I'm very happy that President-Elect Obama is putting a major emphasis on wellness and prevention in his health plan and feel fortunate to be a health policy advisor. I like this approach because it shows that as we gain more understanding as to how dynamic these mechanisms are that can cause physiological improvements, it helps to explain why cost savings may occur very quickly as well.

Ultimately, the reason I'm so passionate about doing this work is because it's about transforming people's lives. We are all going to die; it's just a question of when. For me, the more interesting question is not just how long we live but also how well we live.

It's hard to change lifestyle. I will be the first to acknowledge that. But if you're in enough pain, suddenly the idea of change becomes more interesting. It's like, "Well, it may be hard to change, but I'm hurting so badly I'm ready to try just about anything." When people make these changes and they feel so much better, so quickly, it's a powerful reinforcement.

Your brain literally gets more blood flow within a matter of hours. You can grow so many new brain neutrons your brain gets measurably bigger in just three months. That was thought impossible just a few years ago. Your skin gets more blood, so you age less quickly. Your heart gets more blood, so you can often reverse heart disease. Your sexual organs get more blood, increasing potency in the same way that Viagra works.

People may initially get interested in changing their lifestyle because they are hurting, but what sustains these changes is not fear of dying, it's joy of living.

What is sustainable is pleasure and joy and ecstasy and fun and transforming your life, not risk factor modification, which is boring, or living to be 86 instead of 85, or fear of dying, which is too scary to sustain. People want to feel good. They want to enjoy their life. When you make these changes, most people find that they feel so much better, so quickly, it reframes the reason for making them from living longer to living better.

This work is really about transformation: helping people use the experience of suffering as a catalyst for transforming their lives for the better. People often say things to me like, "Having a heart attack was the best thing that ever happened to me," or, "Having cancer was the best thing that ever happened to me. That's what it took to get my attention to begin making these changes that have made my life so much more joyful and meaningful, and I probably never would have done it otherwise."

Not that anyone looks for suffering. But often, there it is. It's what we do with it. Instead of just literally and figuratively numbing it or killing it or bypassing it with surgery, with drugs, with food or alcohol or cigarettes or those kinds of behaviors, we can work at a deeper level. Not just to address the behaviors but also what is underlying those behaviors. Then we find that people are much more likely to make and maintain choices in their lives that are more life-enhancing than ones that are self-destructive.

The idea that stress plays a role in illness is becoming more and more well defined. It happens both directly and indirectly, directly through mechanisms that we partially understand but not fully, and indirectly through changes in behavior.

What often underlies self-destructive behaviors is loneliness, depression, and isolation. The number-one epidemic in America is not obesity or heart disease, it is depression. The most commonly prescribed prescription drugs last year were antidepressants.

We assume that people want to live longer, but telling somebody that they are going to live longer if they just quit smoking and change their diet is not very motivating if they are depressed and stressed out and unhappy. I have learned that if you don't deal with the underlying loneliness, depression, isolation that is often present, it's very hard to motivate people to change their lives. It's not a lack of information that causes people to smoke. Everybody knows it's not good for you. It's on every pack of cigarettes.

In our studies, I asked people, "Why do you smoke, or eat too much, work too hard, watch too much television, etc? These behaviors seem so maladaptive." And they would reply, "You don't get it—these behaviors are very adaptive, because they help us get through the day."

One patient told me, "I have 20 friends in this pack of cigarettes and they are always there for me and nobody else is. Are you going to take away my 20 friends? What are you going to give me?" Another said, "When I'm depressed, I eat a lot of fat. it coats my nerves and numbs the pain." Or, "I fill the void with food" or "I drink too much to numb the pain" or "I spend too much time on the Internet" or "I spend too much time on video games." There are lots of ways we have of numbing ourselves and distracting ourselves from our pain, literally and figuratively bypassing our pain.

But the pain is not the problem. The pain is a messenger. It is saying, "Hey, listen up! Pay attention, you are not doing something that is in your best interest." Our goal is to help people connect the dots between when we suffer and why. Then, the suffering becomes information, a teacher, a catalyst for change rather than something to be numbed out.

Part of the value of doing science is to redefine what is possible for people, not only in terms of unclogging arteries and making your genes healthier but also in deeper ways. Again, why bother with all that stuff? We are all going to die anyway. The mortality rate is still 100 perecent, one per person. These are more existential questions that are worth asking because if you don't deal with the issue of why get better, then the how doesn't matter. One of the reasons we have consistently shown that we can motivate people to make and maintain bigger changes in lifestyle, achieve better clinical outcomes and even larger cost savings, is that we are working at a deeper level. We are not just focusing on the behavior, but we are also dealing with these underlying issues, which are really important.

It's not all or nothing. You have a spectrum of choices. But to the degree that you can move in a healthy direction, there is a corresponding benefit.

These are issues that cut across the political spectrum because these are just human issues that affect everyone. I love this work because you can really make a difference at a time when, in a real sense, our country is having a heart attack with the rise in health care costs—really, disease care costs—are reaching a tipping point at a time when the economy is melting down. So, the kind of transformational change that we have seen on a personal level we can now see on a social level as well.

There is a wide body of evidence linking stress to immune suppression and also with sudden cardiac death. In one study published in the journal Science, for example, Robert Nerem took cynamologous monkeys who are genetically comparable and put them all on the same diet. One group of monkeys was left alone. For the other group of monkeys, they would periodically introduce a new monkey into the cage. Being very hierarchical like humans, they would fight among themselves to see where they were on the hierarchy. This social instability was very stressful for the monkeys. After a while, the stressed monkeys had 50 percent more plaque in their arteries, even though they were genetically comparable, on the same diet and even their cholesterol and blood pressure levels were not significantly different.

But people aren't rabbits. We have more choices in how we react to stress. As I mentioned earlier, one of the interesting findings in the study that Liz Blackburn did with the women who were chronically stressed and found that their telomeres got shorter was that it wasn't an objective measure of stress. It was the women's perception of stress. How stressed they felt wasn't necessarily related to what was going on in their external environment. Some women reported that they were totally stressed out, even though the stresses didn't seem nearly as big as other women who had more demands but weren't as affected by them.

Consider the analogy to surfing. You can have a big wave and some people find it exciting and fun, whereas other may find it extremely stressful, even life-threatening. When you can manage stress more effectively, then you can often reframe "big waves" as challenges rather than as harmful. In our studies, we teach people very simple techniques of meditation and yoga in ways that are comfortable for them. It can be done in a secular way, it can be done in a religious way, whatever is comfortable for the individual. What they often find is that if they just practice even a few minutes a day of some kind of meditative practice, their fuse gets longer. As one patient told me, "The situation didn't change, but I did."

There are a lot of false choices: "Either I'm going to lead a really interesting and productive, exciting life, and I'm going to get sick and stressed out, or I'm going to be a lump and sing "Kumbaya" and watch my life go by." That isn't the choice.

The more inwardly-defined you are, the more you can quiet down your mind and body and experience more of an inner sense of peace and well being, the more empowered you are. Because, ultimately, people only have power over you if they have something that you think you need. The more inwardly-defined you are, the less you need, so the more powerful you become.

I have had the good fortune to spend some time with powerful, influential people. It's a bit of a cliché to say that they are not always the happiest people, but it's often true. It's hard to tell yourself if you have $3 billion, that if you only had $4 billion you would be happy. Oftentimes when you get to the end of that myth, people are even less happy.

In our work, we present the "stress management techniques" as tools for transforming our lives. Yes, they are powerful ways of managing stress, but they are also much more. They are really about redefining who we are. The ancient swamis and rabbis and priests and monks and nuns didn't develop these techniques to unclog their arteries or perform better at a sports event or board meeting. They can do all those things. But they are really tools for asking, "Who am I? What brings me happiness? Where does my peace of mind come from?"

To the extent that I or anyone else believes that it comes from outside of me, then everyone that I think I need to get something from them has power over me. To the degree that I can say, I enjoy doing all of these things but I don't need them because I know who I am, I'm more inwardly defined, the paradox is that you can often accomplish even more without getting as stressed or sick in the process. And it can be profoundly healing.

We can use science to measure a lot of different things but even Albert Einstein once said, "Not everything that can be counted, counts; and not everything that counts can be counted." Not everything that is meaningful is measurable. Often, the kinds of transformations that we see in people's lives that are the most meaningful to them are the hardest to measure.

Joseph Campbell once said, "I don't have faith, I have experience." Science is not just about what is observed, it's also about what is experienced. It's sometimes hard to measure what's most meaningful just because we don't yet have the tools for it. Awareness is the first step in healing, and science is a powerful tool for raising awareness—but it's not the only one.