Myostatin is a negative regulator of muscle mass and its effects seem to be exacerbated by glucocorticoids.1-3  What that means in English is that myostatin keeps you from getting huuuuge and that the stress hormones like cortisol (a glucocorticoid) make it worse. So stop stressin’, okay?    

But how does it respond to resistance or weight training? Dr. Darryn Willoughby of Baylor University, perhaps the nation’s leading expert in this area (he knows science and he knows how to get huuuuge) looked at 12 weeks of resistance training on the mRNA (messenger RNA) and protein expression of myostatin, myofibrillar protein (as well as other genes) and muscle strength, size and body composition. He took 22 untrained males and randomly assigned them to either a resistance-training group (three times per week; three sets of six reps at about 90 percent of 1-RM; lower extremity exercises) or a control group. Muscle biopsies and blood samples were obtained before and after six and 12 weeks of resistance training.

What did the good doctor find? After 12 weeks of training, subjects increased total body mass, fat-free mass, strength, thigh volume and mass; however, they also increased myostatin mRNA, myostatin, cortisol and myofibrillar protein after six and 12 weeks of training. (And that’s not even the half of it). If you’re confused, join the club.

     Dr. Willoughby concluded this: “Resistance training and/or increased glucocorticoid receptor expression appears to up-regulate myostatin mRNA expression. Furthermore, it is possible that any plausible decreases in skeletal muscle function from the observed increase in serum myostatin were attenuated by increased serum FLRG levels and the concomitant down-regulation of the activin IIb receptor. It is therefore concluded that the increased myostatin in response to cortisol and/or resistance training appears to have no effects on training-induced increases in muscle strength and mass.”1

Here’s My Translation
You can get slackers, make ‘em weight train for 12 weeks, and they’ll get bigger and stronger even though myostatin goes up, cortisol goes up, etc. So, even though research indicates that serum myostatin should inhibit muscle growth, in this study, it didn’t do jack. Dr. Willoughby thinks the increase in something called FLRG (follistatin-like related gene) might have inhibited myostatin from binding to the activin IIb receptor which would then prevent myostatin from interfering with muscle growth.

I guess you might say myostatin regulation of muscle mass (in live human beings who lift weights, not mighty mice, raging rats, or big-ass bulls) is a mystery wrapped in an enigma. Huh? Yeah, me too. 

 Q & A with Myostatin Expert Darryn Willoughby, PhD, Baylor University

Q: What is myostatin? 
A: Myostatin is protein that has been shown to inhibit skeletal muscle growth.

Q: Do any other genes or proteins besides myostatin do the same thing?
A: To my knowledge, not by the same mechanism.

Q: What are these myostatin blockers or inhibitors on the market? Do they work?
A: In vitro studies have shown that extract from cultured Cystoseira canariensis (CC) (I can’t pronounce the dang thing) may bind to myostatin. There’s no good data in vivo on this CC stuff. I just did a study that will soon be published (see Willoughby, DS. Effects of an Alleged Myostatin Binding Supplement and Heavy Resistance Training on Serum Myostatin, Muscle Strength and Mass, and Body Composition. International Journal of Sports Nutrition and Exercise Metabolism. In press.)

We did a 12-week study looking at the supplement containing cystoseira canariensis (CC); the dose ingested was 1,200 milligrams per day of the brown sea algae CC in tablet form for 12 weeks while PLC consumed the equal amount of rice flour as a placebo. At that dosage, it’s not effective at inhibiting myostatin, nor is it effective at preferentially increasing muscle strength and mass or decreasing fat mass when compared to placebo. Maybe there’s a dose-dependent effect.

In theory, it is possible; it sort of reminds me of the old anabolic steroid data from 20 or so years ago where scientists were using doses that wouldn’t even make my daughter’s pet hamster gain weight. I think future work on CC should use doses that are much higher. So, do they work? Not at the doses at which I’ve tested them.

Long-Term Androgen Use
Drink a glass of wine a day and your blood vessels are as smooth as a virgin’s thighs and your heart is as healthy as a racehorse; drink 12 glasses of wine a day and you’re no longer in the “healthy” range of wine consumption; now your body is as used up as a $2 whore. Too much of anything can, in the end, kill you. Now, this may seem like common sense to you and I, but apparently it ain’t so common. For instance, whenever you read an article about steroids in any mainstream newspaper or sports rag, you get the usual litany of “steroids will kill you,” and “steroids will give you heart attacks,” to “steroids will make your penis shrink.”  Well, if you’re a responsible (and smart) journalist, hopefully, you’ll read a little before your print such nonsense. And learn the facts. 

     And the facts are this: Androgens or anabolic steroids can, in fact, be healthy hormones when used wisely and properly. When abused, you can run into problems. The key words here are “use” versus “abuse.” And even for the nimrods with a first grade education, you know there’s a difference. (Think this: eat one Twinkie, nice sugar buzz; eat 20 twinkies, diabetes and fat gut). Be smart; don’t overdose on Twinkies. 

Where Was I? Oh, Science Stuff 
Recent work performed in UCLA looked at very long-term administration of androgens in hypogonadal men (i.e. men who had subpar functioning of their ‘nads).4  They studied 163 hypogonadal men who applied 5, 7.5, or 10 grams of AndroGel (T gel) one percent CIII per day for up to 42 months. That’s 3.5 years for the mathematically challenged! They found that the average serum 5alpha-dihydrotestosterone concentrations and 5alpha-dihydrotestosterone/T ratio slightly increased, mean serum estradiol/T ratio doubled, and mean serum FSH and LH levels were suppressed by T replacement. Sexual function and mood parameters improved rapidly and were maintained throughout T treatment. 

I guess that means they had more sex (with a partner, hopefully). Lean body mass increased and fat mass decreased (better than going through an “Extreme Makeover”). The best part was that these changes were maintained with treatment. Increases in serum bone markers indicated increased bone formation in the spine and hip. There was mild local skin irritation in a dozen subjects. Besides a slight increase in hematocrit and hemoglobin, there were no clinically significant changes in blood counts or biochemistry. However, in three subjects with elevated serum prostate-specific antigen, prostate biopsies showed cancer. Keep in mind that this study was open-label (i.e., not placebo-controlled); therefore, monitoring for prostate disease and other relevant clinical variables is an absolute necessity. 

The bottom line is that in a study of 123 men, the vast majority responded well to androgen (topical) treatment. However, as with any drug, there will be a few individuals who may suffer side effects requiring medical supervision. 
 
References
1.    Willoughby DS. Effects of heavy resistance training on myostatin mRNA and protein expression. Med Sci Sports Exerc, 2004;36:574-82.
2.    Walker KS, Kambadur R, Sharma M, Smith HK. Resistance Training Alters Plasma Myostatin but not IGF-1 in Healthy Men. Med Sci Sports Exerc, 2004;36:787-793.
3.    Roth SM, Martel GF, Ferrell RE, Metter EJ, Hurley BF, Rogers MA. Myostatin gene expression is reduced in humans with heavy-resistance strength training: a brief communication. Exp Biol Med, (Maywood) 2003;228:706-9.
4.    Wang C, Cunningham G, Dobs A, et al. Long-Term Testosterone Gel
            (AndroGel) Treatment Maintains Beneficial Effects on Sexual Function and Mood, Lean and Fat Mass, and Bone Mineral Density in Hypogonadal Men. J Clin Endocrinol Metab,
      2004;89:2085-98.