Why Some People Won't
Be Fit Despite Exercise

Conventional wisdom has it that anyone who really wants to become fit can do so. Just walk or ride a bicycle, swim or run. Speed and endurance will improve and what was once hard will become easy. Lift weights, work with a trainer in a gym, and muscles will grow larger and stronger.

But when a few intrepid scientists began asking if those beliefs were true, they found that fitness, like weight loss, has genetic underpinnings, making it inherently much easier for some to get fit than it is for others. And the facets of fitness are independent, so those who inherit an ability to gain muscle strength may not be able to grow large muscles and those who can easily increase their ability to do aerobic exercise may be thwarted on the weight room floor.

Now, having garnered convincing evidence that genes determine a person's abilities at athletic training, scientists are conducting large and rigorous studies to track down the particular genes, and genetic variants, involved.

The studies do not address the effects of exercise on overall health, whether it helps ward off heart disease or brings longer life, but they are intent on determining the answers to certain health-related questions. For instance, the new research may help find better ways of preventing old people from falling because their muscles are weak.

Is there a way of deciding who needs extra help in maintaining muscle strength or is there an ideal way of augmenting strength in people who are genetically predisposed to be weak?

Muscular dystrophy is even more of a puzzle. Animals with the human gene defect grow bigger and bigger muscles — some, like cats, can become so muscular that even their tongues get huge, unable to fit in their mouths. Children with muscular dystrophy initially grow huge muscles, without trying to do so, and then, after about age 5, their muscles waste away. Can an understanding of the genetic variants that control how large and how strong muscles grow lead to better treatments?

But the research is detecting measures of athletic fitness and, as a consequence, the studies raise ethical questions. Should people be told if they have a gene that will prevent them from ever getting aerobically fit? Should coaches be able to do genetic testing of athletes to learn who is most likely to improve, and who has the genes to be a future star?

Some of the seminal work began quietly more than 20 years ago. Dr. Claude Bouchard, who now directs the Pennington Biomedical Research Center at Louisiana State University, had previously studied obese people by putting them in a metabolic ward where he could keep track of what they ate and how many calories they burned. What would happen, he asked, if he did the same thing with exercise, asking people to train in an exercise laboratory, where he could watch them and measure their efforts?

Some exercise physiologists and sports trainers had assumed that people who said they exercised but never increased their fitness were cheating, either dissembling about the amount of exercise they did or deceiving themselves about how hard they worked when they exercised. But Dr. Bouchard wondered if that was true.

"I asked the question because I had seen people who were known as couch potatoes," Dr. Bouchard said. "They were very sedentary, but when we measured them, there were quite a bit of differences among them. Some had a very nice cardiorespiratory endurance, and at the other end of the spectrum there were people who were very deteriorated from a fitness point of view. I said, `Maybe this problem is caused by genetic differences.' "

The first study began in 1982, with a call for men and women from 18 to 30 who were totally inactive, with a lifetime history of being almost completely sedentary, but who were not particularly fat. One hundred and nine people volunteered. The investigators chose 30, looking for the most extreme examples of inactive people.

"We questioned them and we measured their activity in the last weeks, months and years," Dr. Bouchard said. "They had desk jobs. They would drive a car and never walk. They never did any sport."

After 20 weeks of a training program, in which the subjects worked up to exercising for 50 minutes a day, four days a week, at 85 percent of their maximum heart rates, the results were clear.

"We had large differences in respiration, in maximum oxygen uptake, in the results of muscle and adipose tissue biopsies," Dr. Bouchard said, referring to changes in endurance and ability to exercise at a high intensity as well as changes in body fat and in the sizes of different types of muscle fibers. "Some did not gain in fitness," he added. "Others improved by 50 percent, 60 percent. But they were all compliant."

He did the studies again with pairs of identical twins, finding that if one twin responded well to training, so did the other; if one did not respond, neither did the other.

Now, Dr. Bouchard is directing a national study, taking place at five universities, to search for the genes involved in the training effect. It includes 100 white families and 100 black families, with a total of 742 subjects.

"We tested, trained and retested them with the same program," Dr. Bouchard said. "And we have found the same thing in each of the clinical centers. There are high responders and low responders."

A measurement of a training response is the increase in the amount of oxygen people use when they try to push themselves hard. The more oxygen taken in, the more that enters the blood and is delivered to muscles and so the more intensely the person can exercise, running faster for example.

The average increase after training was 400 milliliters of oxygen, Dr. Bouchard said. But some people had no increase and in some the increase was more than double the average. The range was zero milliliters to 1,000 milliliters. The standard deviation was 200, meaning that two-thirds of the people increased their oxygen consumption by 200 to 600 milliliters of oxygen.

"These are huge differences, but within families, you have aggregation," Dr. Bouchard said. He explained: "Children tend to respond the way their parents do. Siblings tend to respond like each other. The heritability of responsiveness to exercise training was at least as great as it is for body weight, blood pressure and cholesterol."

In the meantime, another study got under way, instigated in part by Dr. Paul Thompson's curiosity about himself. Dr. Thompson, a cardiologist at Hartford Hospital in Connecticut, is a marathon runner who, despite his best efforts, has never been able to grow big muscles. He suspected a strong inherited tendency existed for muscles to respond, or not respond, to training.

"Some people get big just by walking by the barbells," Dr. Thompson said. "Others can lift weights a lot and their muscles don't grow much."

The study, with Dr. Eric Hoffman, a geneticist at the Children's National Medical Center in Washington and others, involves 700 men and 700 women who had not previously lifted weights and who agreed to train in a laboratory. They are trying to build the biceps and triceps muscles of one arm only. The other arm serves as a control while the researchers look for genetic variants that can explain their responses to training.

Although muscle strength and size seem to go together, Dr. Hoffman says they are independent — some people can gain muscle size but not much strength; others can gain strength but not much size. Some gain both. Others gain neither.

But while the study is supported by the National Institutes of Health, which is interested in preventing and treating disease, the investigators are also very aware that their results may be used outside the medical arena. For example, they ask, when the genetic variants, are found, should there be testing for those who want to know their athletic potential? Would people suffer psychological harm if they learned that they were genetically incapable of benefiting from physical training?

To find out, Erynn Gordon, a genetic counselor in Dr. Hoffman's group, said the researchers were assessing how participants reacted to learning their genetic destinies. The subjects took a psychological test, a self-concept assessment, before the research began. When the study is completed, they will be informed of their genetic profiles and will retake the psychological test, allowing the investigators to compare their self images before and after getting the news.

Dr. Bouchard's group has no plans to tell its study participants what their genes reveal about their ability to benefit from exercise. But, Dr. Bouchard said, when he began his work and found that about 10 percent of the people he studied could never improve their fitness with exercise, he did inform some of them.

These were people, he said, who probably knew what was happening. "They did not improve their endurance," Dr. Bouchard said. "They did not lose a gram of fat." While they may still derive something from exercise, a tenuous promise of possibly improved health can be a hard sell for people who want to look better or feel more vigorous.

"If you can monitor things beyond your performance, you may find good reasons to exercise," Dr. Bouchard said. "If not, you have to be convinced that exercise does something good for you, even though you will be the last one to finish each race."