Why Myostatin Inhibiting Supplements and Drugs Don't Often Work

On a recent episode of Super Human Radio I had the opportunity to interview Dr. Stephen Welle. Welle's group over at Rochester University of Medicine published a study that may be the single most important paper since the discovery of Myostatin by Dr. Se Jin Lee.

Many people have tried various OTC and pharmaceutical Myostatin inhibitors with little or no results. This has caused a general feeling that Myostatin inhibitors simply don't work. Well the problem may not be that these supplements and drugs are outright fakes, but instead, that the doses used are not achieving the required suppression levels.


Dr. Welle elucidated in his study that a reduction in active, unbound Myostatin of anything short of a minimumof 60% is basically useless in producing muscle hypertrophy. In fact the growth curve begins at 40% circulating unbound active Myostatin.


The "Sweet Spot" of   Myostatin suppression's fabled extreme anabolic effects occur when total unbound active Myostatin levels drop to 10% or below!!


In the study a unique type of genetically modified mouse was used. This mouse had specific DNA alterations that would allow the researchers to activate the genetic modification after the mouse was already an adult. The thinking was the real value in Myostatin inhibition is what it can do to an adult subject. After all, this is also what we are really interested in since none of us were born Myostatin null humans.


The mice were allowed to mature and then by giving them varying doses of Tamoxifen which would activate the genetic mutation, Myostatin would be suppressed. The number of DNA that would be "turned on" would vary by the dose of Tamoxifen. The more Tamoxifen the genetically modified mouse received, the larger the suppression in circulating active Myostatin.


The varying doses caused Myostatin suppression that yielded active unbound Myostatin from 40% to 95% of baseline in the test subjects. Up to 60% suppression caused no muscle hypertrophy over the controls but the mice that had 60% and above suppression began to grow!


The greatest muscle gains were seen in the mice with 90% to 95% suppression. These mice put on an astonishing 25% pure lean muscle weight in 3 months or less! Now we're talking.



OK, so don't get too excited just yet.  While these results are promising there were a couple glitches. First of all there appears to be a change in collagen production that leads to more brittle muscle tendons that occurred along with the muscle growth. Welle's group is investigating this now and it appears that the muscle gains seen with Myostatin inhibition may come at the price of greater risk of injury.


Also something that was elucidated in earlier studies on Myostatin suppression played out here as well; namely, a reduction in force development. The larger Myostatin-suppression-induced muscle gains do not come with an equal increase in strength and in fact may actually impair the contractile force of the muscle.


I asked Dr. Welle to speculate if Myostatin was to return to normal would the muscle gains remain?  You see, I've always thought that the gains produced by Myostatin inhibition were from hyperplasia and thus a permanent increase in fiber proliferation and density.  Welle said that he felt the gains would reverse if Myostatin was to return to baseline levels because as far as he could see, Myostain inhibition in adult muscle gains were solely from increased sarcoplasmic uptake by the muscle fibers.


This means that if you use a Myostatin inhibitor that gets your circulating Mysotatin levels down below 90% and you see fabled muscle gains, you'll have to keep supplementing with whatever you're using to keep these gains longterm.


You can hear the entire interview here - http://www.superhumanradio.com/rss/2009/SHR_Show_347.mp3

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