DURHAM — First of five parts
In a small, windowless room in the heart of Duke Medical Center, two researchers pushed Jon Kuczynski to the point of exhaustion.
"Five more seconds, push it out, push it out," said Caroline Bishop.
The overweight, 57-year-old landscape architect was wired on a recent morning with 12 contacts for an EKG machine. He wore an awkward mask and mouthpiece to measure his oxygen consumption. Even though he had recently had his cancerous prostate removed, he went at it gamely on the treadmill.
Kuczynski was getting a preliminary dose of what researchers are coming to believe is the closest possible thing to a wonder drug: exercise.
Kuczynski had volunteered for a study to help determine whether exercise might mitigate treatment side effects for prostate cancer patients. The researchers needed him to go until he couldn't go any more to measure his beginning fitness.
"Hopefully, I'll get into the study, and that way I'll be able to force myself to exercise," he said after the test. "I want to get back on track, and there is also the potential that this will help me recover."
More and more, researchers are finding that potential may be hard-wired right into our bodies. From their lanky limbs right down to their DNA, after all, people were designed to move, vigorously and often.
Nowadays, of course, many don't. Waking hours are often spent sitting at the computer, on the couch or in a car seat, hardly stirring except to drift from one sedentary position to another. A national survey in 2008 found that nearly 60 percent of adults didn't engage in more than 10 minutes of vigorous activity per week.
In the past few years, though, scientists - including several running key studies at Duke, UNC, Wake Forest and East Carolina - have found that restoring even some of that missing movement can fuel a startling sweep of benefits for human health. Those effects go well past the long-known basic improvements to the cardiovascular system. In fact, they affect seemingly every major disease.
Regular exercise has recently been shown to sharply reduce the risk of diabetes, stroke, obesity, osteoporosis, anxiety, depression and high blood pressure. Those who exercise may cut the risk of getting colon cancer by nearly one quarter, and those who do get it may cut the chance of the recurrence by more than 50 percent. Recurrence among breast cancer survivors may drop by half when they exercise and follow a healthy diet.
Exercise also can reduce fatigue, fight back pain, improve brain function, blunt the side effects of cancer treatment and perhaps make it easier to break drug addiction. And studies are starting to show that if you do develop some diseases, exercise can improve the outcome of your treatment.
"To get the comparable effect with drugs, you would have to take probably 200 different medications, minimum, to hit each one of the pathways that exercise hits on so many different levels," said Lee Jones, a scientist at Duke.
Jones is leading five federally funded studies into the effects of exercise on patients diagnosed with lung, prostate, breast and colorectal cancers.
A boyish, chipper Englishman who himself exercises twice daily, Jones, 37, doesn't just compare exercise with drugs. He aims a little higher.
"For myself, I think there's three things in terms of your health: what you eat, how much sleep you get, and exercise, and I put them all on the same level. I wouldn't go a day without eating or sleeping, and I wouldn't go a day without exercise."
Evidence piles up
With some of the basic benefits of exercise already documented and even more showing promise, Jones and others have shifted into a new wave of research, including some aimed in part at determining how much exercise and what kind works best for a given patient. Some seek to learn how it might prevent certain diseases altogether.
Jones' team has found repeatedly that some kinds of tumors grow 30 percent to 50 percent slower in mice that are exercised. He suspects a major reason is the overall health of the body, or host, surrounding the tumor.
"Exercise, of course, is one of those interventions that can fundamentally change the host, and I think we can change the host from a host where cancer loves to be - it's like the best hotel in the city - to the worst hotel in the city," he said. "I think exercise can make the host environment essentially toxic to cancer cells, and we've got to make it a very unfavorable place for cancer cells to live, a hostile environment."
For now, much of the research involves helping people recover from disease, and cancer is a major focus. That's partly because the number of survivors is climbing rapidly, but they are often in poor health, debilitated by the disease and the side effects of treatment.
"A lot of people with cancer now aren't dying from it, so how do we optimize their ability to participate in life and, secondly, stop recurrence?" said Dr. Catherine Alfano, a program director in Cancer Survivorship at the National Cancer Institute, which is funding several exercise studies.
"All available evidence indicates that exercise can reduce your risk of recurrence. But OK, what is exercise really doing?" she said. "That's a key question some of this research is working on."
The results of the research could eventually change the way that a host of diseases are prevented and treated. Jones and Alfano said that if the evidence continues to pile up, cancer could become a qualifying diagnosis for insurance companies to pay for exercise therapy as a medical treatment for various diseases, just as they do for cardiovascular disease.
Jones is a polished, passionate speaker on some of the most complex aspects of what exercise does for humans, from psychology to cellular behavior. But when asked about the downside of exercise, he went silent. Five seconds passed. Ten seconds.
"Of exercise? Well, umm..." Then he mumbled under his breath. "I don't know if there are any."
There are some risks, and he eventually named a few, including heart attack. But he noted that is often due to pre-existing conditions caused by a lack of exercise.
Since exercise costs so little, there isn't the same kind of private financial gusher behind this research that pharmaceutical companies pour into new drugs. But with lawmakers focused more and more on trying to hold down the nation's rising health care costs, the prospect of inexpensive prevention and treatment prospects for a host of problems has agencies such as the National Institutes of Health willing to pony up, so the grants keep coming.
UNC has just set up a lab in its cancer center with machinery so sophisticated that it can measure subtle changes in the bone density of living subjects. Researchers there and at Duke, Wake Forest and East Carolina University have millions of dollars in grant-funded studies under way and more planned.
What they have been finding might surprise folks who think exercise is only good for the muscles and the cardiovascular system.
At Duke, Dr. James Blumenthal is a leading researcher in studying the effects of exercise on mental health. One study he led showed that exercise could be just as effective in treating depression as powerful drugs such as Zoloft.
Aided by recent advances in knowledge about subjects such as genetics, these scientists are beginning to learn more about the depth to which exercise affects the body.
At Duke, the mouse study looked at knee arthritis, which in humans has long been associated with being overweight.
A basic belief has long been that the cartilage - the soft tissue that acts as a buffer between the hard bones - simply wears out quickly or is more easily damaged by the extra load.
The researchers fed some mice high-fat diets and forced them to run. They found that even carrying extra weight, the knees of the mice that ran weren't wearing out as expected.
Obesity can cause cells throughout the body to become inflamed, triggering a chain of ill effects, among them perhaps causing or worsening arthritis. The fat cells continued to produce inflammatory molecules that have been linked with arthritis, but the researchers believe that the exercise disrupted the cascade of ill effects. They have a study on arthritis and exercise under way with humans.
Scientists examining other health effects from exercise believe similarly complex mechanisms are at work, and are digging deep to try to understand them.
"They're looking at the evidence that it can, say, reduce recurrence of cancer and saying, OK, but what is it really doing?" Alfano said. "Is it affecting tissue? Is it improving cardiac function? Acting on a pathway such as inflammation, which we know can affect cardiovascular health and cancer?"
The results now starting to come in, Alfano said, are pointing to the need for a major trial with several thousand people enrolled to look at whether exercise can extend life in cancer survivors.
It's never too late
There aren't just benefits for the sick.
As Alfano says, there is much talk in Washington these days of preventive medicine. Studies show, for example, that kids who exercise have better brain function. Research at ECU has shown that if kids are physically active in class for 10 minutes, they will be able to focus better on the academic content.
Overall, on-task behavior increased by 8 percent. For the kids least on task to begin with, on-task behavior increased by 20 percent. This demonstrated that the physical activities helped all kids, and most helped the kids who needed it the most.
And even in your 80s, it's not too late to start.
Elaine Murphy, 92, a retired bank teller who lives in Chapel Hill, hadn't been physically active since ballet classes at age 16. After open heart surgery and a couple of falls in her driveway, though, she enrolled in a simple balance class started by UNC researchers who were trying to reduce fall rates among the elderly.
These falls can end in broken hips or other injuries and are a huge public health problem, as they drain resources and often send victims to bed where, instead of recovering, their health starts its final slide.
Murphy hasn't fallen since taking the class and in the course of taking it got hooked on exercise. Now she hits the workout room at the Seymour Senior Center five days a week, three hours a day, nimbly stepping from the rowing machine to the treadmill to the elliptical machine and chatting up fellow exercisers as she goes.
"It even helps you when you're getting out of bed," she said one recent day while adjusting a weight machine. "I didn't exercise before, but this helps my walking, and even climbing stairs got easier. You develop some muscles that help you."
The best combo?
Several of the studies under way are looking at how exercise works in conjunction with another factor, such as changes in diet or a specific drug regimen. They also want to know which of two approaches - weight training or aerobic forms of exercise such asrunning - work better, or whether they are more effective together.
For five years at UNC-Chapel Hill, researchers have been running a study, called Get Real & Heel, with breast cancer survivors who have completed treatment. It's designed to study whether exercise and biofeedback working together can help improve the patient's health, which, even with successful treatment often takes a huge hit. Their cardiovascular function in particular drops sharply and often doesn't improve.
One day a couple of weeks ago, Deb Nickell, 61, was sitting at a computer in the Get Real offices, looking at a scene of water and woods as new-age music played and a soothing voice gave her instructions about focusing her thoughts. A sensor attached to her finger monitored her brain waves and heart rate as she steadied them.
After a few minutes, she walked into the adjacent room and stepped onto the treadmill. Under coaching by a graduate student, she did the other part of her therapy session, which included a moderate workout.
Nickell, who owns a small shop on Durham's Ninth Street, enrolled in the Get Real & Heel study after doctors at UNC recommended it. The combination of mental and physical therapies is helping fix the two parts of her life that cancer and treatment hit hardest, she said: the physical and psychological.
"I had never felt as weak physically and emotionally-spiritually," she said.
"This program kind of gives me tools, and it's great that it's a study, but it is really changing lives."
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