AICAR and GW1516

the "Exercise Pill"

Scientists have discovered that two chemicals, AICAR and GW1516, may produce some of the physical benefits of exercise. Exercise, as stated though out this web site, is one of the best things you can do for yourself. It has multiple physical and psychological health benefits. It does involve work and determination (which add to the psychological benefits). Most everyone would rather take a pill than run six miles.

How does it work?

When we exercise, our muscle cells make several adaptations to improve our physical performance. There are multiple chemical signals that tell our cells what adaptations to make. Two of the many signal receptors on our muscle cells' surfaces are AMPK and PPARd (PPAR-delta).

PPARd/GW1516

In mice that are genetically programmed to have an overactive PPARd receptor, it was found that even without physical conditioning, their endurance was nearly twice as much as normal mice. The GW1516 chemical stimulates the PPARd receptor. Mice that have been given GW1516 were able to run 60-75% longer and farther. This chemical has been shown to be active in humans as well.

Scientists found that GW1516 given to mice mostly had beneficial effects in the fast-twitch muscles (quick strong contractions) over the slow-twitch muscles (repetitive endurance contractions). They also found that just giving the drug to mice did not increase their running endurance. However, when these mice also were made to exercise and given GW1516, there was an increase of slow-twitch muscle fibers by 38%. Also, muscle cells made more mitochondria (the power plants of cells).

There are several other genes that were activated when the mice were given GW1516 and made to exercise. Some of these regulate the storage and uptake of fat. Others caused muscle remodeling and an increase in aerobic metabolism capacity.

AMPK/AICAR

AMPK is another receptor on muscle cell surfaces that is activated by exercise. AICAR can be taken orally and turns on the AMPK receptor. It has been shown to increase endurance in mice by 45%.

After treating mice with AICAR for 4 weeks, some fat mass was reduced and oxygen consumption (i.e. metabolism) was increased. They also were able to run faster and longer without any physical training.

The combination of AICAR and GW1516

When GW1516 and AICAR were given together in mice that did not exercise, 40% of the genes were activated that were turned on in the mice that both exercised and took GW1516. Most of these genes affect muscle performance. Thus, many exercise signals were activated in the cells even though the mice had not exercised.

Side Effects

These chemicals are still in the experimental stage. Not until humans take these drugs on a large scale will their side effects be fully known.

These chemicals may open the door to yet another performance enhancing drug. For the ultracompetative athlete who wants to win at all costs, enhanced physical endurance in a pill would be very appealing. One of the main scientists who worked on this study has developed a urine test to detect the drug. He has made it available to the International Olympic Committee.

Comments

Taken by themselves, AICAR produces some of the beneficial effects of exercise on muscle cells. GW1516 in combination with exercise also produces beneficial effects on muscles. The scientists who studied this suggest that medicines that mimic the effects of exercise may play a role in treating muscle diseases such as wasting or frailty and in obesity. As noted above, this is all still experimental. The full benefits and side effects are yet to be known.

Although these researchers have discovered how to positively activate many of the cellular signals that are present during exercise, it is unlikely that these drugs can completely induce the positive effects of regular exercise.

The psychological improvements would almost certainly be left out. There is a myriad of nerve signals in the brain that are activated during exercise. Endorphins produce the "runner's high" that cause some people to say that they are "addicted" to running or other exercise.

Sports and exercise give people a sense of accomplishment and an outlet for stress. They can also foster a positive competitive drive which helps people to be successful in life. There is a great deal of social interaction that goes into playing sports and exercising as well. None of this can be replaced by a pill. (At least not yet.)

For those who are severely obese and cannot/will not exercise, a "exercise pill" may be of great benefit. However, for everyone who can, regular exercise will likely remain a cornerstone of health and happiness.