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).

References:

• 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.

Ripped & Buffed vs. Skinny and Sinewy: Training Velocity, not Load, Appears to be Sole Determinant of Exercise Induced Shifts from Slow- to Fast-Twitch Muscle Fibers.

Image 1: Who would you like to be?
And how do you train to achieve
his physique?

Sprinter or marathon runner? Ripped and buffed or skinny and sinewy? Although this is, after all, a question of muscle vs. fat, bone and tissue mass, it is upon closer examination as much a qualitative question, as it is a quantitative one - a question that may well be influenced by the way you train!

Unlike our adipose tissue which has almost unlimited capacity to grow, the size of our muscles appears to limited by a number of factors, among which the individual fiber-make-up, i.e. the ratio of slow-oxidative endurance-type fibers (type I) to fast-twitch type IIA (fast-oxidative glycolytic), and fast twitch IIX (fast glycolytic) seems to play an important role, when it comes to getting big and buffed or skinny and sinewy.

Figure 1: Slow- and fast-twitch faber composition in athletes and non-athletes (data based on Carrol. 1998; Widrick. 2002)

As the data in figure 1 goes to show, athletes, unlike untrained individuals, who have about the same amount of fast and slow-twitch fibers, exhibit discipline specific adaptations in muscle fiber composition, with sprinters having the lowest and middle distance runners the highest ratio of slow to fast twitch muscle fibers. According to data from Aagard and Andersen, Bergh et al. and Fry et al. (Berg. 1978; Aaagard. 1998; Fry. 2003), the range of slow to fast twitch fiber ratios extends from ultra-endurance runners with a 90:10 slow to fast twitch ratio down to weight lifters and sprinters with a minimum of 20:80 slow to fast twitch fiber ratio.

Muscle fiber type and weight loss: Contrary to what you may have guessed, or read elsewhere, obese patients with a higher amount of oxidative slow-twitch fibers have been shown to lose weight easier than their "heavier muscled" peers. In a 2002 study Tanner et al. report (Tanner. 2002):

With weight loss intervention, there was a positive relationship (r = 0.72,P < 0.005) between the percentage of excess weight loss and the percentage of type I fibers in morbidly obese patients. These findings indicate that there is a relationship between muscle fiber type and obesity.

Image 2: For someone who already got morbidly obese, a higher ratio of type II fibers may well be counter-productive if his/her overall goal is weight loss.

Another result of the same study, which could easily be misinterpreted as politically incorrect is the genetically determined higher raio of type II muscle fibers within the African American part of the female study population, which made it increasingly harder for these women to burn the fat. And just in case, you still wonder why a type I fiber, something obviously only skinny people have in excess would help with losing fat, just think about the term "oxidative muscle fiber" for a moment, then add to that the experimental observation that type I fibers have greater mitochondria volume densities than type II fibers (Sullivan. 1978) and you will realize that a highly oxidative muscle fiber is more valuable when it comes to burning fat than a glycolitic one, reagardless of whether or not the latter may "look" better ;-)

In a recent review of the literature Wilson et al. provide the following biological explanation for the differences that exist between endurance and strength athletes (Wilson. 2011):

[...], type I fibers have been observed to have both greater mitochondria volume densities as well as capillary-fiber contact length when compared to type II fibers.  In addition, mitochondria volume density was highly correlated (r = 0.99) with O2 diffusion coefficients across three different muscle groups (retractor, sartorius, soleus) suggesting greater aerobic capacity in type I fibers.

While type I muscle fibers will thus figuratively carry their owners in 80 days around the world, type IIX and IIA fibers exhibit a 10x and 6x greater peak power and a 4x and 3.3x greater contractile velocity than their oxygen-hungry slow twitch cousins.

Figure 2: Relative peak power and contractile velocity of fast twitch fibers vs. slow twitch fibers (data based on Wilson. 2011)

The reason that the two guys from image 1 do not only perform but also look completely differently, lies yet in the greater capacity of type II fibers for exercise-induced hypertrophy (Schoenfeld. 2000). The relative number of type II to type I fibers is thus of paramount importance, if you want to look like a sprinter - not like a marathon runner and if you want to lift heavy weights instead of running cross-country. Fry et al., for example found strong correlations (r = 0.94; almost "causative") between the percentage of type IIA fibers and 1 repetition max snatch performance in national caliber Olympic athletes (Fry. 2003). Now the obvious question is: "How can I influence my individual fiber composition, or is this simply genetically determined?"

It stands to reason that genetics is a major determinant of fiber composition, but, hardgainer or not, with appropriate training and nutrition everyone can - at least to a certain degree - shift his muscle fiber make-up from a slow-twitch oxidative to a fast-twitch glycolytic type, even without the use of clenbuterol and other beta-2 agonists which hav been shown to trigger respective shifts from type I to type II muscle fibers in a rodent model (Zeeman. 1988).

Training for shifts in fiber composition

From Wilson et al.'s review of the literature it becomes quite obvious that standard exercise regimen, like jump squats at either 30% or 80% do not provide satisfactory results for someone looking to increase the number, not the size of his glycolytic muscle fibers (Wilson. 2011). In a study by Liu et al. (Liu. 2008), a 5x3RM bench press protocol, performed 3 times per week for 6 weeks, on the other hand, triggered a shift within the type II fibers. It increased the percentage of type IIA fibers from 44.9% to 66.7%, but decreased the type IIX fibers from 33.4% to 19.5%, thus leaving the percentage of slow twitch type I fibers unchanged. A second group from the same study who used a more versatile routine, with the same 5x3 regimen on Mondays, 10x concentric-repetition bench press throws at 30% of their 1RM on Wednesday and 10 stretch-shortening type push-ups on Friday for 5 sets, each, were able to increase the number of type IIA muscle fibers (from 47.7% to 62.7%) without decreases in the number of type IIX fibers, but a profound -50% reduction of slow-twitch oxidative fibers (from 18.2% to 9.2%). Wilson et al. go on and cite several other studies that were able to show the modulatory (increase in type II, decrease in type I) effects of high-velocity contractions on muscle fiber composition (Wilson. 2011) and corroborate that results with findings from other studies which corroborate these results with ...

[...] findings that the percentage of type I fibers may be increased with various types of aerobic training protocols such as endurance cycle training (+12% Type 1) and long distance running (+17% Type 1), [where, on the other hand] studies indicate that sprint training may facilitate the change of slow twitch fibers to fast twitch fibers.

Interestingly, Hortobagyi et al. were able to show that laziness taken to the extreme, i.e. 3 weeks of knee immobilization, also reduced the amount of type I fibers (-9%) and increased the number of type IIX fibers (+11%) in 48 recreationally active men and women (Hortobagyi. 2000). These results should yet be treated with appropriate caution and I would strongly advice against lying on the couch to increase your propensity for muscle growth by decreasing the number of slow twitch and increasing the number of fast twitch muscle fibers, because "recreational activity", for most people, consists of aerobic type of exercises, playing soccer, tennis or whatever - all sports that by and out of themselves would trigger shifts towards a more oxidative (predominant type I) muscle composition. It is thus not surprising that refraining from such activities for 3 weeks would reverse those changes.

So how should you train, then?

In view of the paramount importance of speed, not load in the few experiments which challenge the hitherto established paradigm that muscle fiber composition was largely determined by genetics and transformation was possible only within type II fibers, i.e. from type IIA to type IIX and vice versa, the incorporation of respective training techniques, e.g. concentric-repetition bench press throws at 30% of your1RM, as they were used in the study by Liu et al. (Liu. 2008), into a more versatile hypertrophy-specific routine which would

1. trigger a hypertrophy response, on "classic" strength training days (like 3x5 or 3x8-10), and
2. increase propensity for growth, on "speed-rep" days with exercises like plyometric push-ups, concentric-repetition bench press throws at 30% 1RM, etc.

would appear to be the most reasonable way to train for anyone out there, who does not belong to the "genetic elite" of born sprinters.