Exercise in a Pill?

Too good to be true, right?

Right - but this new research (in mice) is still pretty cool.

In the research journal “Cell” (Volume 134, Issue 3, 8 August 2008, Pages 405-415) - the abstract appears below, scientists were able to mimic SOME of the effects of exercise training in different groups of mice.

Even though the research was done more than a year ago, the publication in Cell at the end of July (2008) generated a storm of media coverage with headlines like “Sit back to get in shape” and “Couch potatoes rejoice - pills do the work of exercise” - Hey, whatever sells magazines and newspapers...

Even though the effects described in mice are somewhat limited (more on that below), the results provide tantalizing evidence that it may be possible to use drugs to improve the ability of muscle cells to burn fat, extend endurance, and maintain muscle mass - whether you exercise or not.

Drug companies are certainly interested...imagine being able to take a pill someday that reduced obesity or protected you from diabetes or treated muscle-wasting diseases like muscular dystrophy. Both GlaxoSmithKilne and Schering-Plough have been involved in research on the 2 drug compounds used in the recent mouse studies (AICAR, which is an AMPK agonist and “GW1516”, which is a PPAR-delta agonost). Schering has recently licensed AICAR (also known as acadesine), but GW1516 was dropped by Glaxo because of toxic side effects in humans.

When given to mice, GW1516 enabled mice to run for about 3 hours until exhaustion (compared to their normal 2 hours in untreated control mice) - but it only worked in “training” mice (who were regularly exercising) - and NOT in sedentary mice. AICAR, on the other hand, improved running endurance in mice whether or not they were training - so the couch potato mice were able to run as if they were well-trained.

The underlying metabolic effect of these drugs appears to be an improvement in the ability of slow-twitch muscle cells to burn fat - and effect that improved endurance in these studies, but may also help to treat obesity (but which remains to be investigated).

Certainly, we need to view these results within their proper context - these are mice being given experimental drugs - and the effects observed here may not translate at all to humans. The best that human endurance athletes can currently do to improve endurance performance is to supplement with cordyceps, rhodiola, and eurycoma to improve oxygen utilization. Carnitine and adenosine can also be beneficial for fat burning, but they need to be taken at such high doses for effectiveness that they rapidly become prohibitively expensive.

Thanks for reading (and check out the original abstract below),

Shawn Talbott, PhD

I also blog on a daily basis at:

www.ShawnTalbott.com (about various health and wellness topics)
www.SupplementWatch.com (about the pros and cons of dietary supplements)
www.GetUpSlimDown.com (about weight loss, metabolism, and feeling better)
www.WisdomofBalance.com (about traditional Asian medicine, or TAM)
www.WickedFastSportsNutrition.com (about nutrition for endurance athletes)
www.MetabolismCoach.com (about metabolism, nutrition, exercise, and energy)

AMPK and PPARδ Agonists Are Exercise Mimetics

Vihang A. Narkar1, Michael Downes1, Ruth T. Yu1, Emi Embler1, Yong-Xu Wang4, Ester Banayo3, Maria M. Mihaylova2, Michael C. Nelson1, Yuhua Zou1, Henry Juguilon1, Heonjoong Kang5, Reuben J. Shaw2 and Ronald M. Evans1, 3,

1Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA 2Molecular and Cell Biology Laboratory, Salk Institute, La Jolla, CA 92037, USA 3Howard Hughes Medical Institute, La Jolla, CA 92037, USA 4University of Massachusetts Medical School, Worcester, MA 01605, USA 5Marine Biotechnology Laboratory, School of Earth and Environmental Sciences, Seoul National University, Seoul 151-747, South Korea

Summary
The benefits of endurance exercise on general health make it desirable to identify orally active agents that would mimic or potentiate the effects of exercise to treat metabolic diseases. Although certain natural compounds, such as reseveratrol, have endurance-enhancing activities, their exact metabolic targets remain elusive. We therefore tested the effect of pathway-specific drugs on endurance capacities of mice in a treadmill running test. We found that PPARβ/δ agonist and exercise training synergistically increase oxidative myofibers and running endurance in adult mice. Because training activates AMPK and PGC1α, we then tested whether the orally active AMPK agonist AICAR might be sufficient to overcome the exercise requirement. Unexpectedly, even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. These results demonstrate that AMPK-PPARδ pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance without exercise.