Working out does more than simply prevent health problems. It can actually treat disease.
For a study published in 2019 in the Journal of the Neurological Sciences, a team of doctors at the Cleveland Clinic in Ohio split up 59 people with Parkinson’s disease into two groups. Three days a week for eight weeks, both groups completed a 40-minute exercise session on a stationary bicycle. One of the groups rode at a high-intensity pace while the other group rode at their own slower pace.
By the end of the study period, both groups — but especially the high-intensity group — scored significantly better on several measures of mobility, including tasks that tested their flexibility and strength. A month after the study’s publication, one of its leaders received a $3 million grant from the National Institutes of Health (NIH) to study whether exercise can actually slow the progression of Parkinson’s disease. If the study is successful, exercise could become the first known treatment to slow the progression of the condition.
Parkinson’s is a neurodegenerative condition that affects roughly one million Americans. Slowly but ceaselessly, people with the disease experience cell death in a part of the brain known as the basal ganglia, which serves many functions but primarily controls movement and coordination. Hand tremors and jerky movements are typical during the early stages of Parkinson’s. Over time, these symptoms spread and worsen and are accompanied by a steady loss of stability, flexibility, and coordination as well as problems with thinking, mood, and memory.
According to a 2018 research review from the Mayo Clinic, no drug has ever demonstrated the ability to slow the progression of Parkinson’s disease. But the same Mayo Clinic review concludes that physical activity provides a “direct brain effect” that can both improve symptoms among people with Parkinson’s and, in some cases, maybe even delay the disease’s advance. How is this possible? Research has found that exercise can raise the brain’s levels of certain chemicals that reduce the loss of neurons and promote improved thinking and cognitive function in people with Parkinson’s. In other words, there’s evidence that exercise has the ability to selectively target and improve multiple aspects of the disease through a number of underlying neurochemical mechanisms.
For maladies ranging from autoimmune diseases to depression, doctors and medical researchers are embracing the idea that physical activity has tremendous therapeutic power for those who are unwell.
“Exercise is absolutely the most effective therapy we have for Parkinson’s, more effective than any drug,” says Michael Zigmond, a Parkinson’s researcher and professor emeritus in the Department of Neurology at the University of Pittsburgh. Zigmond says exercise exerts a number of benefits in the brains of people with Parkinson’s — benefits that not only combat the disease’s deleterious effects but that also address many of the changes associated with old age. “It increases protective neurotrophic factors, it lowers oxidative stress, it reduces inflammation, it repairs DNA damage, it increases dopamine release, and it does this all over the brain,” he explains. “No drug can do that.”
The idea that exercise is good for the human body is a truism. No one doubts it. According to a large 2015 perspective paper on the health benefits of exercise published in the journal Cell Metabolism: “The human species evolved to perform and endure habitual [physical activity] … it is not surprising that its absence can lead to devastating physiological and clinical consequences.” But until recently, few people regarded physical activity as a form of medicine capable of managing or treating disease.
That’s changing. For maladies ranging from pain conditions and autoimmune diseases to cancer, heart disease, and mental health disorders like depression, doctors and medical researchers are embracing the idea that physical activity has tremendous therapeutic power for those who are unwell.
“Regular exercise may be the most powerful medicine we have — more powerful in most cases than any pill or procedure,” says Dr. Robert Sallis, a family and sports medicine physician at Kaiser Permanente. “We literally have thousands of years of data, going back to Hippocrates, that exercise has a powerful therapeutic effect.”
The history of exercise as medicine
The world’s leading medical minds have long recognized the healing power of physical activity. “There were physicians in India around 600 B.C. who regarded physical activity as medicine, and exercise was a big part of ancient Chinese medicine as well,” says Jack Berryman, professor emeritus of medical history at the University of Washington.
During the reign of the Roman Empire and for more than 1,000 years after its collapse, medical practice and theory were heavily influenced by the opinions of the physician Galen, who could rightly be called the father of lifestyle medicine. According to some of Berryman’s published scholarship, it was Galen’s view that human health was largely determined by a person’s approach to the “things nonnatural,” which included diet, sleep, and exercise. Galen believed that a moderate approach to each was a cornerstone of both disease prevention and therapy.
During the 18th and 19th centuries, physicians embraced “heroic” medical procedures such as bloodletting, sweating, blistering, and the use of tinctures containing mercury or other poisonous compounds — all of which were thought to restore the body’s essential fluids to a healthful state of balance. “George Washington died because the top physicians in the country at that time bled him to death,” Berryman says.
But Galen’s beliefs never completely died out. The concept of “physical education” and the importance of exercise for human health blossomed among many American doctors during the 1800s. Physicians at that time oversaw the construction of many of the country’s first gymnasiums, and a major component of their training and messaging to patients involved the primacy of regular physical activity for the maintenance of health and the treatment of disease.
But then, by the early part of the 20th century, germ theory and other major insights into illness and disease revolutionized the medical profession. Preventive and lifestyle medicine receded as professional doctors turned their attention to the treatment of illness with drugs and surgery, Berryman says. At the same time, physical education began to focus more on sports and games that catered to athletes and less so as a means for the average person to maintain or improve health. “Physical education wasn’t focused on individual health anymore, and medicine wasn’t really focused on lifestyle or exercise anymore,” Berryman says. “It took a while for the two to come back together.”
While some doctors today are still resistant to the idea that exercise can outperform pills or medical procedures, many are embracing the idea that exercise is a potent treatment for a variety of diseases.
The “wonder drug”
The Academy of Royal Medical Colleges is the U.K. equivalent of the U.S. National Academy of Medicine. In a 2015 report partly titled “Exercise: The miracle cure,” the Academy’s chair, Dame Sue Bailey, discusses the “enormous” health and well-being benefits associated with physical activity — both for the prevention of disease and for disease management.
If exercise were a drug, Bailey writes, “it would be classed as a wonder drug.” Maybe most wondrous of all is exercise’s ability to treat — and in some cases reverse — a disparate range of medical conditions and symptoms via a spectrum of underlying mechanisms of benefit.
Kaiser Permanente’s Sallis says Type 2 diabetes is the classic example. For years, the drug metformin was considered the gold-standard treatment for diabetes. Metformin effectively lowers the liver’s production of glucose and also increases the body’s sensitivity to insulin — both of which are beneficial for people with Type 2 diabetes or prediabetes. Metformin makes the World Health Organization’s list of essential medicines, which are the ones it deems to be the most effective and safe for the world’s most common maladies. But doctors were surprised when, in 2002, a large government-funded clinical trial known as the Diabetes Prevention Program found that the combination of diet improvements and 150 minutes of weekly exercise were roughly twice as effective as metformin at preventing the development of Type 2 diabetes among people at high risk for the disease.
“Exercise is like a separate dose of insulin that always works.”
“I think the Diabetes Prevention Program was eye-opening for the medical community because it was one of the first large randomized controlled trials comparing a lifestyle intervention to a drug intervention,” says Wendy Kohrt, a professor of medicine and the Nancy Anschutz Chair in Women’s Health Research at the University of Colorado. Kohrt says the goal and hope of the trial was to show that lifestyle changes could match the clinical benefits of metformin. The fact that lifestyle changes vastly outperformed the drug — especially among older adults — was a shock, she says.
How does exercise help people with diabetes? A 2016 position statement from the American Diabetes Association summarizes the evidence on exercise and declares that both aerobic and strength training can significantly and rapidly improve measures of glycemic control and insulin sensitivity. “Physical activity creates muscle contractions, which allows the muscles to take up blood glucose directly without the need for insulin,” says Sheri Colberg-Ochs, first author of the position statement and a professor emerita of exercise science at Old Dominion University. “Exercise is like a separate dose of insulin that always works,” she adds.
Along with Type 2 diabetes, autoimmune disorders are among the most common causes of chronic disease in the U.S. The term “autoimmune” refers to medical conditions in which the human immune system inappropriately attacks healthy cells, nerves, or tissues. More than 80 conditions fall under the autoimmune disease umbrella, according to the NIH, and these include rheumatoid arthritis, lupus, celiac disease, inflammatory bowel disease, and multiple sclerosis. There’s evidence that rates of autoimmune diseases have exploded in recent decades. And while experts have struggled to determine the precise drivers of this unhappy trend, there’s strong evidence that exercise can relieve or ameliorate the symptoms of a diverse array of autoimmune disorders.
“In people with multiple sclerosis, we’ve made the case that exercise could be influencing the progression of the disease through at least three different pathways,” says Robert Motl, a professor and associate director of research at the University of Alabama, Birmingham, who has studied the effects of exercise in people with MS. As with many other medical conditions, multiple sclerosis tends to get worse faster when a person has comorbid issues such as heart disease, Type 2 diabetes, or hypertension. Exercise blocks or treats all of these comorbidities, which is the first pathway by which it can help people with MS, he says.
At the same time, he says that regular exercise can increase the blood’s levels of inflammation-blocking immune system chemicals while also lowering the blood’s levels of inflammation-promoting immune system chemicals. Runaway inflammation fuels the symptoms and progression of MS — as it does for many other diseases. And so exercise’s ability to reduce inflammation is a big deal, he says.
“There’s also emerging data that exercise affects the structure and function of the central nervous system itself,” says Motl. For people with MS, the immune system attacks and breaks down the myelin that surrounds and protects the nerves of the brain and spinal cord. “The disease gets worse for people with multiple sclerosis because they lose myelination around the nerves, and eventually they lose the nerves themselves,” he explains. “But we’ve shown that exercise can slow down that loss or in some cases even prevent that demyelination.”
How? Exercise involves and activates every organ of the body, including the brain. And similar to the way a muscle grows larger in response to strength training, the brain seems to experience growth in response to exercise. “The brain is an adaptive organ,” Motl says. By boosting the brain’s levels of growth-promoting chemicals and metabolic activity, “exercise is a stimulus that builds it up,” he says.
Exercise and the mind
According to the latest figures from the U.S. National Institute of Mental Health, about 1 in 14 Americans experienced an episode of major depression during the past year. The numbers are more dire among young adults and adolescents; roughly 1 in 8 Americans aged 12 to 25 experienced a depressive episode last year, and that’s true of fully 1 in 5 adolescent women.
Depression is categorized as a disease of the mind, but it has grave implications for the health of the body. Writing in the journal Circulation, doctors at the American Heart Association lay out the evidence that young people diagnosed with depression are at elevated risk for early-onset heart disease and arterial disease. Recent studies have also found that the risk of early death is much higher among people with mental health disorders, including depression, compared with the general population even after excluding suicide. Depression is associated with a dysregulation of the immune and nervous systems, and it disrupts metabolic and hormone activity — all of which may promote the development of diseases, argues a 2018 review in Frontiers in Psychiatry.
Most people with depression are treated with a combination of drugs and psychotherapy. But regular exercise may prove to be a more potent aid than either of them. “Physical activity improves the symptoms of depression through mechanisms both above and below the neck,” says Martino Belvederi Murri, first author of the Frontiers review and an assistant professor in the Institute of Psychiatry at the University of Ferrara in Italy.
Murri says that regular exercise helps regulate the brain and blood’s levels of neurotransmitters like dopamine and serotonin in ways that appear to improve and stabilize mood and also bolsters thinking. “[Exercise] also tends to reduce the neurotoxic effects of inflammation in the brain while promoting the growth of newborn neurons and the connections between existing ones,” he says. “This explains why the brains of people who are physically active tend to be functionally and structurally more healthy than those of people who are sedentary.”
It may be helpful to think of a sedentary brain and body as akin to a plant locked in a dark closet. No matter how well the plant is fed or watered, it will die without sunlight. The same seems to be true of a human body denied regular physical activity.
There’s research linking exercise to improvements among people with anxiety disorders, bipolar disorder, and other mood disorders. There’s also abundant evidence that exercise can help manage chronic pain conditions such as arthritis. While some of this evidence is deemed weak by modern scientific standards, that weakness is mostly due to a lack of well-funded clinical exercise trials. But all that’s about to change, thanks in large part to the launch of the largest-ever government-funded study on the effects of exercise on the human body.
Looking to the future of exercise as medicine
While more and more doctors today recognize the therapeutic power of exercise, experts say there’s still a ways to go. “In general, I don’t think that the majority of the medical community believes that exercise can be as effective as whatever drugs they might prescribe to treat or prevent a certain condition,” says Kohrt, the University of Colorado professor.
Part of the hesitancy, she says, is that the biochemical mechanisms undergirding exercise’s therapeutic benefits are, at this point, not well understood. But she and a large, nationwide group of researchers are working to change that.
In June 2015, the NIH announced it was launching a $170 million, multifaceted research effort to better understand the effects of exercise on the human body. Known as the Molecular Transducers of Physical Activity Consortium, or MoTrPAC (pronounced “motor-pack”), the trial will include thousands of people and many more animal and lab specimens. Its aim is to develop a detailed map of the molecular, genetic, epigenetic, and other changes that take place in the body during and after exercise. The trial is currently in the process of enrolling approximately 2,000 adults along with a smaller group of kids.
When the trial is complete, “we will have this wealth of foundational evidence that will help scientists determine when exercise may or may not be an appropriate therapeutic option to be prescribed in place of a pill.”
“Right now we understand how exercise is good physiologically — how it helps us feel better or stronger,” says Russell Tracy, one of the MoTrPAC trial’s leaders and a professor in the Department of Pathology and Laboratory Medicine at the University of Vermont Larner College of Medicine. “What we don’t know is, at the molecular level, what is happening that results in those physiological improvements.” Another open question, he says, is why exercise works a certain way in some people but not in others. “While exercise is almost universally beneficial, it doesn’t yield the same benefit in everyone,” he says. MoTrPAC will attempt to fill in these knowledge gaps.
Kohrt is another of the MoTrPAC trial’s leaders. She says that when the trial is completed, “we will have this wealth of foundational evidence that will help scientists determine when exercise may or may not be an appropriate therapeutic option to be prescribed in place of a pill.” Rather than having to guess at which type or amount of exercise may be optimal for a given patient, doctors and researchers will be able to use the maps MoTrPAC generates to come up with solid, evidence-backed exercise recommendations.
Kohrt says MoTrPAC should start producing early results within the next two years, and the molecular map it aims to produce should be finished within three to four. At that point, it will “open the doors” to a new era of research into the role of exercise in medicine and human health, she says.
In the meantime, experts say there’s already enough evidence to guide people — both the well and the sick — toward appropriate forms and amounts of exercise. “We know the optimal dosage range, and it’s 150 minutes a week of moderate exercise,” Sallis says, echoing the U.S. Department of Health and Human Services’ current physical activity guidelines. “If you want to get the bulk of the benefits of exercise, that’s really all you need — you don’t need to run marathons.”
Others reiterate this view. For people with heart disease, “the perfect amount is 150–300 minutes per week of moderate-intensity physical activity . . . or 75 minutes of high-intensity activity,” says Dr. Carl Lavie, medical director of cardiac rehabilitation and prevention at New Orleans’s Ochsner Heart and Vascular Institute. Lavie says moderate-intensity activities include walking and light sessions on a bike or elliptical machine and that running, vigorous cycling, and swimming are examples of high-intensity activities. “Unfortunately, few comply with this advice, but there are benefits even at lower levels [of exercise],” he says.
Sallis agrees and says working “little snacks” of exercise into the routines of daily life — advice that public health experts have been voicing for decades — really do make a difference. “Taking the stairs at work or parking farther away so you have to walk — these all add up,” he says.
“We’re so enamored with the power of the pill or the procedure, and part of that is because our system rewards physicians monetarily for pushing those even when they’re not effective,” he says. It’s time for that to change. “I think a lot of patients today are receptive to messages about exercise and want to avoid taking a pill.”
Exercise, he adds, is more than just a way to prevent America’s most pressing health problems. “It can treat and cure disease.”
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