Anabolic Edge By Jose Antonio, PhD
Selective Androgen Receptor Modulators (SARM)
19-norandrostenedione (NOR) is readily metabolized to nortestosterone, also known as nandrolone (durabolin) after its in vivo administration. A recent study showed that NOR binds with high selectivity to the AR. In vivo (meaning in living animals) experiments in orchiectomised rats (i.e., no balls) demonstrated that subcutaneous treatment with NOR resulted only in a stimulation of the weight of the levator ani muscle; the prostate and seminal vesicle weights remained completely unaffected. Now that is a good thing! Who needs a big prostate? Makes peeing not so fun. Thus, NOR, if given subcutaneously, and in contrast to its metabolite nandrolone, very selectively stimulates the growth of the skeletal muscle but has only weak androgenic properties. In a sense, it acts like a SARM.
In another investigation, scientists found something called “AC-262536,” which was identified as a potent and selective androgen receptor (AR) ligand. A two-week chronic study in castrated male rats indicated that AC-262536 significantly improves anabolic parameters in these animals, especially in stimulating the growth of the levator ani and in suppressing elevated LH levels. In sharp contrast to testosterone, AC-262536 has weak androgenic effects, as measured by prostate and seminal vesicle weights. Thus, AC-262536 represents a novel class of selective androgen receptor modulators (SARMs) with beneficial anabolic effects. So what would happen if you combined AC-262536 and NOR? You’d have one helluva anabolic one-two punch!
Shorten Their Life? Huh?
Sometimes scientists just say dumb things even in peer-reviewed publications. In a recent study, nutritional supplementation and anabolic steroid (AS) use in adolescent males and females in a multistate, cross-regional area were studied. A secondary purpose of the study was to investigate the knowledge, beliefs and sources of education on nutritional supplementation and AS in these students. Use of at least one supplement was reported by 71.2 percent of the adolescents surveyed. The most popular supplements used were multivitamins and high-energy drinks. The use of supplements to increase body mass and strength, and to reduce body fat or mass, increased across grade and was more prevalent in males than females. Interestingly, the number of students who self-reported AS use was 1.6 percent (2.4 percent males and 0.8 percent females). Not very many, actually. But the following statement has got to be up there for the “bonehead statement of the year” award:
“Adolescents also seemed willing to take more risks with supplements to achieve their fitness or athletic goals, even if these risks reduced health or caused premature death.”
Where is the evidence that any supplement causes premature death? You know what causes premature death? Being a fat-ass, eating junk food every day, and falling in love with your remote control and your Wii. Why do scientists focus on such minute nonsense when folks out there smoke (hey, you know that causes premature death) like chimneys, drink like camel in the desert and eat like it’s a Nathan’s overeating contest?
No! Not that fake crap found in stinkin’ seaweed. I mean, come on. Did you actually think that a supplement company could come up with a real myostatin inhibitor? Please! However, the drug world has indeed come up with something. As you may already know, myostatin is an endogenous negative regulator of muscle growth and a novel target for muscle diseases. Or in English, the more myostatin your body makes, the less muscle you are likely to have.
Scientists performed a safety trial of a neutralizing antibody to myostatin, MYO-029, in adult muscular dystrophies (Becker muscular dystrophy, facioscapulohumeral dystrophy and limb-girdle muscular dystrophy). Never mind wondering what all those dystrophies are. The important point is that this is a HUMAN study on an actual myostatin inhibitor. In this double-blind, placebo-controlled, multinational, randomized study, 116 subjects were divided into sequential dose-escalation cohorts, each receiving MYO-029 or placebo (Cohort 1 at 1mg/kg; Cohort 2 at 3mg/kg; Cohort 3 at 10mg/kg; Cohort 4 at 30mg/kg). What did they find? MYO-029 had good safety and tolerability, with the exception of cutaneous hypersensitivity at the 10 and 30mg/kg doses. The bioactivity of MYO-029 was supported by a trend in a limited number of subjects toward increased muscle size using dual-energy radiographic absorptiometry and muscle histology. Clearly, folks with various dystrophies are a different population than your normal male athlete. It would be intriguing to say the least to see what would happen if you administered this to a male bodybuilder. And on top of that, stack it with SARMs.
And I thought it was merely a sleep aid. In this study, scientists compared the weight, insulin-like growth factor-1 (IGF-1) expression and anatomy of the soleus muscle in growing castrated rats treated with testosterone or melatonin. In this study, adult male rats were castrated, then given testosterone or melatonin injections. Of course, if you cut a rat’s balls off, it will result in smaller muscles, specifically the soleus weight and fiber diameter shrunk; however, testosterone and melatonin administration increased their size. IGF-1 immunostaining observed in the satellite cells and periphery of the myofibers was least intense in the castrated group. Strong staining of IGF-1 was observed in the testosterone- and melatonin-administered groups. The anatomy of myofibrils in the testosterone- and melatonin-injected groups was similar to that in sham groups in view of structure, meaning both hormones helped maintain the integrity and structure of the muscle. Thus, at least in this study, melatonin is as effective as testosterone in the prevention of atrophy.
Nature vs. Nurture
What causes criminal behavior? If you answered, “When mommy didn’t hug me enough,” then go to the head of the class. Just kidding, of course. Actually, there is some interesting data related to the androgen receptor which points to a genetic link. In essence, we know that androgens mediate their functions through androgen receptors (AR). The two triplet repeats in the AR gene (CAG and GGN) have been extensively studied in diverse clinical conditions and antisocial personality disorders. Several studies have reported either higher levels of testosterone among rapists or the correlation of shorter CAG repeats with criminal activities. This current study revealed significantly shorter CAG repeats in the rapists (mean 18.44 repeats) and murderers (mean 17.59 repeats) compared to the control men (mean 21.19 repeats). The criminals who committed murder after rape had a far shorter mean repeat length (mean 17.31 repeats) in comparison to the controls or those convicted of rape or murder alone. In brief, this study suggests that the reduced CAG repeats in the AR gene are associated with criminal behavior. If you don’t know or don’t care what a CAG repeat is, no problem. Just keep in mind that what this study basically shows is that having certain “genetic traits” may be related to certain bad behavior; on the flip side, it may also be related (other genes) to good behavior, etc. I’m a big believer that genes have a much more profound influence on who we are than nurture.
Jose Antonio, PhD, is vice president of the National Strength and Conditioning Association. He has a PhD in muscle physiology and is chief executive of the International Society of Sports Nutrition.
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Wagner KR, Fleckenstein JL, Amato AA, et al. A phase I/IItrial of MYO-029 in adult subjects with muscular dystrophy. Ann Neurol, 2008.
Oner J, Oner H, Sahin Z, Demir R, Ustunel I. Melatonin is as Effective as Testosterone in the Prevention of Soleus Muscle Atrophy Induced by Castration in Rats. Anat Rec, (Hoboken) 2008;291:448-55.
Rajender S, Pandu G, Sharma JD, Gandhi KP, Singh L, Thangaraj K. Reduced CAG repeats length in androgen receptor gene is associated with violent criminal behavior. Int J Legal Med, 2008.