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Exercise in a Bottle?

August 1, 2008

By ALAN ZAREMBO

By Alan Zarembo

Los Angeles Times

Scientists have discovered what could be the ultimate workout for couch potatoes: exercise in a pill.

In experiments on mice that did no exercise, the chemical compound, known as AICAR, allowed them to run 44 percent farther on a treadmill than those that did not receive the drug.

The drug, according to the researchers, changed the physical composition of muscle, essentially transforming the tissue from sugar-burning fast-twitch fibers to fat-burning slow-twitch ones – the same change that occurs in distance runners and cyclists through training.

The researchers said the drug’s fat-burning ability also could help reduce weight, ward off diabetes and prevent heart disease – the benefits of daily aerobic activity without the perspiration.

“It’s an amazing piece of pharmacology,” said David Mangelsdorf, a pharmacologist at the University of Texas Southwestern Medical Center in Dallas, who was not connected with the research. “You’re getting the benefits of exercise without having to do any work.”

It is unknown whether the drug has any benefit for athletes who actually work out – or any human for that matter, since the research has so far only involved mice.

“The mouse doctors and cell biologists are of course quite enthusiastic about these things, but the human doctors are a little more reticent,” said Dr. Benjamin Levine, a cardiologist who leads the Institute for Exercise and Environmental Medicine at Presbyterian Hospital of Dallas, and who was not involved in the study.

But lead researcher Ronald Evans, a molecular physiologist at the Salk Institute for Biological Studies in the San Diego community of La Jolla, said he has already been contacted by dozens of athletes and overweight people who have heard about his research from several lectures he has given on the subject.

Evans said he has notified world anti-doping officials, who are now scrambling to implement a test for it before the Beijing Olympics start next week.

The compound, which is naturally produced in tiny amounts in human muscle cells and has been studied for decades, is readily available through Web sites that cater to researchers. One site was offering it for $120 a gram.

Evans predicted that in the wake of his study, published Thursday in the journal Cell, it will “fly off the shelves.”

With more research, he said, the drug might one day be used as a treatment for muscle wasting, obesity and as a means of allowing bedridden patients to reap the benefits of exercise.

The drug has been tested in humans for a variety of conditions related to the heart and repeatedly passed basic safety tests.

“It was found to be a quite safe drug, at least at the doses we were using,” said chemist Paul Laikind, who patented the compound in the 1980s and began testing it as a means of preserving blood flow to the heart during surgery.

The compound is now owned by drug maker Schering-Plough Corp., which is trying to develop the compound as an intravenous infusion for the prevention of ischemia- reperfusion injury, a complication of bypass surgery.

The discovery of AICAR as a potential couch-potato exercise pill grew out of Evans’ continuing research on creating super mice.

In 2004, he made headlines for engineering “marathon mice.” By injecting a single gene into the nucleus of a fertilized egg, he created mice born with more efficient muscles, faster metabolisms and stronger hearts.

He wanted to know whether it was possible to achieve the same effect using a drug.

His team didn’t start with AICAR, but another compound known as GW1516, which drug maker GlaxoSmithKline is trying to develop as a drug to raise levels of HDL, or good cholesterol. The drug is known to stimulate the production of a protein known as PPARd, which in turn activates the genes that boost endurance in muscle cells.

In sedentary mice, the drug had no effect on endurance.

Only when the drug was combined with exercise did it give the mice an advantage. After five weeks of training, mice that got the drug were able to run for more than three hours, improving 68 percent more than mice that received only the training.

When the researchers dissected the mice that got the drug, they found that the number of high-efficiency muscle fibers had increased 29 percent.

“That’s a huge increase,” Evans said. “That’s the kind of stuff that Lance Armstrong and endurance athletes aim for.”

study

The researchers said the drug’s fat-burning ability also could help reduce weight, ward off diabetes and prevent heart disease.

Originally published by BY ALAN ZAREMBO.

(c) 2008 Virginian – Pilot. Provided by ProQuest Information and Learning. All rights Reserved.




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