The elusive pill to mimic workouts

Gretchen Reynolds / New York Times News Service /

Published Jul 24, 2013 at 05:00AM

Two newly published studies investigate the enticing possibility that we might one day be able to gain the benefits of exercise by downing a pill, rather than by actually sweating. But while some of the research holds out promise for an effective workout pill, there remains the question of whether such a move is wise.

The more encouraging of the new studies, which appears this week in Nature Medicine, expands on a major study published last year in Nature. In that study, a team at the Scripps Research Institute in Jupiter, Fla., reported that a compound they had created and injected into obese mice increased activation of a protein called REV-ERB, which is known to partially control animals’ circadian rhythms and internal biological clocks. The injected animals lost weight, even on a high-fat diet, and improved their cholesterol profiles.

Unexpectedly, the treated mice also began using more oxygen through the day and expending about 5 percent more energy than untreated mice, even though they were not moving about more than the other animals. In fact, in most cases, they were more physically lazy and inactive than they had been before the injections. The drug, it seemed, was providing them with a workout, minus the effort.

Intrigued, the Scripps scientists, in conjunction with researchers from the Pasteur Institute in France and other institutions, set out to see what their compound might be doing inside muscles to provide this ersatz exercise. They knew that their drug increased the potency of the REV-ERB protein, but no one yet knew what REV-ERB actually does in muscles. So they began by developing a strain of mice that could not express very much of the protein in their muscle cells.

Those animals proved to be anti-athletes. One of the hallmarks of regular aerobic exercise is that in muscles, it increases the number and vigor of the mitochondria, the cellular structures that help to generate energy while consuming oxygen. But these animals’ muscles contained woefully few mitochondria.

As a result, the animals had diminished endurance, with a maximal oxygen capacity about 60 percent lower than normal. They reached exhaustion on treadmill testing long before their unaffected labmates.

But when, in a separate part of the experiment, scientists added their compound to isolated muscle cells from the deficient mice, the cells began pumping out far more REV-ERB. Those cells, subsequently, began creating large numbers of new mitochondria and strengthening the existing ones.

Finally, the scientists injected their compound into sedentary mice, stimulating their production of REV-ERB beyond what would be considered typical. When they set the sedentary mice loose on little treadmills, they ran “significantly longer both in time and distance” than untreated animals, the authors wrote, even though they had not been training beforehand.