Exercise in a Pill? Not So Fast

July 31, 2008— -- While new research suggests that drugs could enhance or even mimic the effects of exercise, many researchers say that the notion that you could skip the treadmill and pop a pill is premature.

A team of scientists led by Ronald M. Evans, an investigator at Howard Hughes Medical Institute and professor at the Salk Institute's Gene Expression Laboratory, studied two drugs that trigger genetic changes in the body -- changes that are typically stimulated by exercise and can ultimately lead to improved muscle functioning and energy-burning abilities.

And in mice, at least, the drugs seem to show some positive results. When given to exercise-trained mice, the first drug, known as GW1516, increased their running time by 68 percent and distance by 70 percent.

The second, called AICAR, increased running time by 23 percent and distance by 44 percent -- but in mice that were "couch potato[es]," Evans says. It was as if, he says, the mice had achieved the "impossible goal" of gaining muscle tone and endurance without having exercised.

The research was published Thursday in the online edition of the journal Cell.

"Perhaps the most significant finding is that one can actually develop a pill that can confer exercise," Evans says.

He says that such a drug could help people who are unable to exercise during long hospital stays, those who are bedridden and those who cannot exercise for other reasons.

"Basically this is a way that you can take a pill and get the benefits of exercise, even though you can't exercise," Evans says.

Not so fast, other experts caution. First of all, they say, the study was done in animals.

Though Dr. David L. Katz, director of the Prevention Research Center at Yale University School of Medicine, calls the study "provocative," he adds that "the methods are strong, but the relevance to people is uncertain at present."

Others experts agree, and warn that the link to humans is still unknown.

"This is a well-done study with important implications if the same effects hold true in humans -- a big if," says Dr. Mark D. Miller, professor and head of the division of sports medicine at the University of Virginia in Charlottesville.

"I have read hundreds of studies done with mice or rats investigating compounds that cause weight loss in the little creatures," says Joanne P. Ikeda, nutritionist emeritus in the Department of Nutritional Sciences at the University of California, Berkeley. "None of these compounds had the same effect in humans."

Endurance Versus Exercise

Still, if future research can prove that these drugs are effective in humans as well as mice, many people may stand to benefit.

Katz says that such drugs could help the physical conditioning of people who have congestive heart failure and other conditions that would prevent exercise.

"So the real issue here is that medication can help condition muscle," Katz says. "It is a wild and unjustified extrapolation to go from there to the notion that a pill could provide all of the benefits of exercise."

Dr. Linn Goldberg, head of the Division of Health Promotion and Sports Medicine at Oregon Health and Science University, calls it a "leap of faith" to suggest that increasing conditioning or aerobic capacity is the same as performing exercise.

"[Exercise] not only involves skeletal muscle fibers, but the main muscle we depend on, the heart," Goldberg says.

He adds that believing that you've exercised by taking a pill is "like being placed on third base and thinking you hit a triple."

The actual act of exercise can help improve cholesterol levels, lower blood pressure, reduce mental stress and strengthen bones, Goldberg says. A pill that offers an increased endurance might lack those other benefits.

"People should not be misled to think that they can take a pill with their latte and skip the gym," Miller says. "There is no way that is going to happen."

He says that the potential side effects of the drugs are currently unknown, and could possibly include muscle injury or premature aging of muscle cells.

Another Abuse for Athletes?

Though researchers are developing the drugs for medical purposes, Evans says he is concerned that a specific group of people will have the greatest interest.

"I believe that one of the first early adopters of this kind of drug will be athletes wishing to get a jump on the competition," he says.

He says he believes that after the announcement of his research, athletes will begin searching for ways to get their hands on AICAR, even though it is only being used for research purposes at the moment.

"Believe me, you'll see the amount of research the athletes are doing goes way up," he says.

Many experts consider this a viable concern. Katz calls the drug "another potential substance of abuse by athletes." Cooper agrees, saying that, "The world does not need any more performance-enhancing drugs for athletes."

Evans says that he and other Howard Hughes Medical Institute researchers are working with the World Anti-Doping Agency (WADA) to develop a highly sensitive test that can detect both GW1516 and AICAR in blood and urine.

It may be available in time for next month's summer Olympics in Beijing, he says.

And though this new research may spark interest from athletes and couch potatoes alike, Katz says that achieving "better living" by taking medications is ill-advised.

"There are inevitably costs, and usually unanticipated toxicities," Katz says.

He poses a simple question: "What's wrong with getting the benefits of exercise from exercise?"