For those who cannot exercise, it could be the answer: rather than spending hours in the gym, the benefits of fitness training could be delivered in a tablet.

The prospect of an “exercise pill” might be music to the ears of couch potatoes, long-distance truck drivers and stressed-out office workers, but researchers believe it could transform the lives of people who are unable to exercise because of obesity or serious physical disabilities.



Hopes for such a pill emerged on Tuesday from scientists who found that an experimental drug allowed mice to run on a treadmill for 270 minutes before exhaustion set in. Mice that went without the drug lasted only 160 minutes before reaching their physical limit.



The endurance boost was accompanied by other apparent health benefits, scientists found, leading mice who had the drug for eight weeks to put on less weight and better control their blood sugar levels, suggesting a pill might also help people with diabetes.



Scientists led by Ronald Evans at the Salk Institute in San Diego made the discovery after they set out to explore what endurance meant on the molecular level. “If we really understand the science, can we replace training with a drug?” he said.



They turned to a drug known as GW501516 which had previously been shown to improve stamina and burn fat faster. Through a series of tests with mice on treadmills, Evans found that the drug changed the activity of nearly 1000 genes. Many of the genes that became more active were involved in the breakdown and burning of fat. But other genes were suppressed, including some that convert sugar into energy.



Writing in the journal Cell Metabolism, the scientists describe how the findings might explain why runners, cyclists and others athletes can “hit the wall” when they push themselves hard. The drug makes the body burn fat faster, but also burn sugar more slowly. The upshot is that, on the drug, the drop in blood sugar level that is responsible for the feeling of hitting the wall happens much later than normal.



“In endurance sport competitions, such as cycling, marathon runs, race walking and cross-country skiing, ‘hitting the wall’ is a dramatic demonstration of sudden and complete exhaustion,” the scientists write. But the drug, which achieves its effects through muscle proteins called PPARD, “is sufficient to dramatically improve endurance capacity.”



“Exercise activates PPARD, but we’re showing that you can do the same thing without mechanical training. It means you can improve endurance to the equivalent level as someone in training, without all of the physical effort,” said Weiwei Fan, the paper’s first author.



The compound was originally developed by what is now GlaxoSmithKline and a US company called Ligand pharmaceuticals in the 1990s. Intended to treat metabolic and cardiovascular disease, it was later abandoned, apparently after a number of studies found that high doses might cause cancer.

But despite the drug being dropped commercially, scientists continue to study the compound. A decade ago, tests in animals showed that it could potentially boost stamina. The finding spawned a black market for the drug, and its subsequent abuse by some athletes in the 2008 Beijing Olympics. The following year, the World Anti-Doping Agency banned the drug and warned that it was not safe.



Ali Tavassoli, professor of chemical biology at Southampton University who was not involved in the latest study, said that any “exercise pill” that scientists develop could potentially be abused, not only by athletes, but by horse trainers and others.



“But there are groups of people who for one reason or other cannot exercise, people with real problems, and you could potentially have a pill that gives them some of the benefits of exercise,” he said. “A pill of this sort might allow them to a place where they can start to exercise for real.”



Tavassoli is not convinced that an exercise pill will arrive any time soon though. “Personally, I am not certain that such a pill would be possible. There’s a big difference between showing in an organism that you can mimic exercise over the short-term and demonstrating the long-term effects of doing this.”



“Someone with obesity or diabetes might be taking a pill for 40 or 50 years. What happens when you take a drug like this for that long? What happens to you? These are big unanswered questions,” Tavassoli said. “I can’t see these things getting regulatory approval.”



Louise MacKenzie, a pharmacologist at the University of Hertfordshire, who has studied GW501516, said it was once considered a “wonder drug” because of its potential to treat a number of medical conditions. But while the compound appears to have benefits at low doses, it can have bad side effects at high doses. “It goes from being remarkably healthy to being the complete opposite, there’s no in-between,” she said. Nevertheless, MacKenzie said the drug was a good “starting block” for scientists hoping to find new ways to treat patients. “I can definitely see a future where the problems are solved. You just need to have enough clever scientists working on them,” she said.

