Tuesday, November 26, 2013

High Intensity Training + Mesterolone Yield Muscle- and Fiber-Type Specific Size Gains Of Up To 100% & More

Want to learn more about fiber types? ➫ review past SuppVersity articles
I am not telling you a secret, when I say that testosterone alone - in the absence of training - will lead to significant increases in skeletal muscle mass (if you think that sounds like a secret you must have missed my previous article from the "Intermittent Thoughts on Building Muscle" series | read more). To a certain extend, the same is true for DHT (learn more), and - as a recent 6-week rodent study by Karina Fontana, Gerson E. R. Campos, Robert S. Staron and Maria Alice da Cruz-Höfling shows even by the structurally similar, orally bioavailable derivative Mesterolone (aka Proviron), which produces pretty drastic, fiber-type specific increases in muscle size, when it is administered in super-physiological doses for 6 weeks (Fontana. 2013).

AAS +/- HIT = ?

Basically the question the researchers from the universities of Campinas (Brazil) and Ohio had in mind, when they came up with their study protocol was: Do anabolic steroids exert direct effects on the fiber type composition and cross-sectional area of skeletal muscle fibers of sedentary and high-intensity, aerobically-exercised transgenic mice.
DHT & T ⇔ fat & muscle Comp | more
Why did the researchers select 1 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-on (Mesterolone), not testosterone? At first sight it may seem stupid not to go for straight testosterone, but Fontana et al. deliberately chose "DHT", for two reasons: (1) oral bioavailability and (2) no hepatoxicity ➫ no injection induced wound-formation or liver damage that would skew the results.
As the scientists point out, the aim of the study was thus "to investigate the role of mesterolone in a supposed catabolic environment" (Fontana. 2013) and answer the following detail questions:
  • Does the interaction of anabolic hormone treatment and high-intensity aerobic exercise produce an increase in muscle mass and redistribution of skeletal muscle fiber types? 
  • Are muscles with distinct metabolic and contractile properties (i.e., fast/glycolytic vs. slow/oxidative) differently modulated by the anabolic androgenic steroid treatment combined with a high-intensity, endurance-type training program? 
  • As such, three skeletal muscles were studied under these experimental conditions: soleus (SOL), tibialis anterior (TA) and gastrocnemius (GAS). 
To be able to do so, assigned their transgenic mice (these mice have been "modified" so that they have a lipid metabolism that's closer to the one of human beings) to four different groups, i.e.
Table 1: Overview of the incremental exercise program the rodents in the "EX-" (=exercise) groups performed on a treadmill 5x per week
  • Sed-C - sedentary control
  • Sed-M - sedentary + 3x2mg/kg* Mesterolone per week
  • Ex-C -5x/week HIT exercise + gum arabic placebo
  • Ex-M - 5x/week HIT exercise + 3x2mg/kg* M per week
*Note: The scientists claim to administer "supraphysiological" against that background we must assume that we are talking about 2mg/kg for a human (if that was the rodent dose, the human equivalent) would be 12-15mg and that's clearly not "supra-physiological" - 3 doses of 150-200mg of Mesterolone which comes in 25mg pills, on the other hand, would be "supra-phyiological".
After 6 weeks, the animals were sacrificed, their muscles harvested and an analysis of the entire range of pure and hybrid fiber types was conducted.
Mesterolone is not DHT: Anonymous was kind enough to remind me that the original version of this article did not make a clear distinction between DHT and 1-alpha-methyl-DHT aka Mesterolone (or Proviron). He did however mix his facts up, because contrary to A.'s claim Mesterolone has a 3x higher binding affinity for the androgen receptor in skeletal muscle than "regular" DHT (Saartok. 1984). With a 4x higher affinity for SHBG, it is however difficult to predict the real-world differences. This is particularly true in view of the fact that the growth response could be triggered by non-receptor mediated mechanisms, as well.
Just in case you don't remember all the details you've learned about the different fiber types in previous SuppVersity articles, keep in mind that type I fibers are mainly oxidative, they use fat as a "preferred" substrate and will get you from A to B when you walk or jog. The type II fibers, on the other hand are "glycolytic", this means, that they rely heavily on glucose. Their prerogative are explosive / fast contractions and they carry the lions share of the weight you through around at the gym.
Figure 1: Muscle weight and body weight (in g) at the end of the study (Fontana. 2013)
Against that background it's quite telling that the tibialis, the muscle with the largest amount of Type IIA and Type II AD fibers, fast twitch fibers that can use both, glucose and fat as fuel, is the only muscle where we don't see the following relation between the muscle weight: EX-M > EX-C > SED-M > SED-C.
Figure 2: Detailed analysis of the changes in fiber type composition of soleus, tibialis and gastrocnemius muscle; all data expressed relative to sedentary control (Fontana. 2013)
If you take a closer look at the detailed fiber type analysis the researchers conducted (Figure 2), you will see that a similar trend can be observed in the "intermediate" muscle, the gastrocnemius (see grey arrow). The effects the DHT clone had on the "oxidative" soleus, on the other hand, were in no instance more pronounced than those of the 20-60min treadmill running regimen (see Table 1, for details).
Suggested: "Serum & Intramuscular Testosterone, DHT and Androgen Receptor Response to High vs. Low Volume Training" | more
So what can we learn from this study? (1) Contrary to the common believe that muscle building was a prerogative of testosterone, Mesterolone (Proviron, DHT) can obviously build muscle, as well - at least, when it is administered at supra-physiological doses (see comment above; plus: don't do that at home ;-). (2) Despite the fact that the orally bioavailable DHT derivative does build muscle, even in the absence of physical activity, the changes are really pronounced only, when it is combined with intensive exercise. (3) Astonishingly, even running, i.e. a simple endurance exercise has significant anabolic effects on both oxidative (this is what you would expect) and glycolytic (this is actually surprising) muscle fibers. (4) This effect is highly amplified by Mesterolone - particularly in the Type IIA + IIAD fibers of the gastrocnemius, which has a particularly high content of "glycolytic only" Type IIB fibers (>50% in the exercise groups).  

This fourth and point, is actually the most interesting one. It does after all confirm what I mentioned only casually in previous articles about DHT, the true androgen, which is rapidly deactivated in the muscle and does still appear to play an important role in the structural changes your musculature undergoes, when you exercise. Speaking of changes, I guess you will already have realized that the highly pronounced increase in muscle fiber size of the type II fibers stands in line with the often-touted "strength building" effects of designer steroids with structural resemblance to DHT. The overall mass gains - and this is something you may have heard about said AAS, as well, on the other hand, are rather mediocre (see Figure 1).
  • Fontana, Karina, et al. "Effects of Anabolic Steroids and High-Intensity Aerobic Exercise on Skeletal Muscle of Transgenic Mice." PloS one 8.11 (2013): e80909. 
  • Itil, Turan M., et al. "Male hormones in the treatment of depression: effects of mesterolone." Progress In Neuro-Psychopharmacology 2.4 (1978): 457-467. 
  • Ly, Lam P., et al. "A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency." Journal of Clinical Endocrinology & Metabolism 86.9 (2001): 4078-4088. 
  • Saartok, Tönu, Erik Dahlberg, And Jan-Åke Gustafsson. "Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin." Endocrinology 114.6 (1984): 2100-2106.
  • Singh, Keerti, Asha Singh, and A. K. Sarada. "Assessment of mesterolone therapy in oligospermic males." www.ijpsi.org Volume 2 Issue 3 March 2013.