Does lifetime natty really matter?

Probably.

Is there a threshold of anabolic steroid use that alters myogenic potential forever?

It looks like Yes, but forever is a long time.

Does resistance training and anabolic steroid use have an additive or even synergistic effect on myogenic potential?

Likely, but we do not have the data in humans, nor do we know if this is a threshold or a gradient-like effect.

 

To begin to delve into this somewhat esoteric BRO topic let’s hit 5 or so intertwining points.

 

  1. “Testosterone-induced muscle fiber hypertrophy is associated with a dose-dependent increase in myonuclear number…Muscle growth during postnatal development or hypertrophy is dependent on the addition of myonuclei to muscle fibers”

-Sinha-Hikim et al. 2003

 

  1. “Satellite cells appear to be crucial to maximizing the hypertrophic response to resistance training. The primary role of satellite cells appears to be their ability to retain a muscle’s mitotic capacity by donating nuclei to existing myofibers.
  2. Satellite cell function might be particularly important in well-trained people because the size of myofibers would necessarily reach the upper limits of their myonuclear domain (maybe a threshold of 26%).
  3. Myonuclei are maintained over time even after long periods of detraining and the corresponding muscle atrophy.”

-Dr. Brad Schoenfeld – Science and Development of Muscle Hypertrophy

 

  1. “Prior steroid exposure conferred a distinct advantage to the muscles, with a 44% increase in CSA rather than the 17% increase observed in controls. These benefits were not transient. When the muscles were induced to hypertrophy 3 months after steroid treatments had ended (the mouse equivalent of 10 years of human lifespan), the steroid-treated group displayed a 31% increase in CSA compared to a modest 6% in placebo controls. Taken together, these data suggest that: (1) once you acquire a myonucleus, it is essentially permanent; and (2) more nuclei translate into greater capacity for regrowth, which presumably translates into enhanced muscle strength and/or speed.”

-Schwartz 2013 The Journal of Physiology

 

Now that we have that we have covered those topics we can start to look at the data we have in humans, unfortunately all untrained which is a huge asterisk.

“Significant increases in satellite cell number were observed only in men who were treated with supraphysiological doses of testosterone enanthate.”

-Sinha-Hikim et al. 2003

However, this was WITHOUT resistance training and the 125 mg per week group (around a TRT dose) did not see a significant hypertrophic response, nor did they see changes in satellite cell number.

Which leads us to two intersecting pretty big questions that I can only speculate about in humans.

  1. Does lower dose anabolic steroid use combined with resistance training increase myonuclei and satellite cell number more so than resistance training alone? Given the animal data I would guess there is an additive, maybe even synergistic effect (we do see an additive effect on muscle hypertrophy). I don’t believe we have this study in humans, but if someone knows about it please send it my way.
  2. The next jump is where things get really interesting to me. We know guys get more jacked when they get on higher doses of gear (average bodybuilder dose is 1100 mg per week) and lift weights. That is a duh. Maybe not so duh is that they have also likely raised the ceiling on their muscle building potential forever (through increased myonuclear potential and perhaps also through epigenetic memory). This may ruffle your feathers if you are an anti-doping purist. BUT, if we do see an additive/synergistic effect of testosterone on myonuclear potential at the higher end of physiological, when combined with resistance training this all of a sudden makes the time frame of the mid-teens to early twenties where testosterone tends to top out really really important. You don’t lift hard in that age range and you potentially miss out on laying down the myogenic potential for later in your training career. Maybe, but a lot of us do see this anecdotally in trainees who find resistance training much later in life, some of them just can’t seem to put on the same degree of muscle we would expect, granted there are a tons of factors involved here the biggest likely being effort over time and a lack of grit, but this idea of critical period of myogenic potential is extremely interesting to me.

The next study is an RCT by Kvorning et al. which is pretty much the complete opposite of the study above. These researchers suppressed endogenous testosterone production and then put participants through eight-weeks of strength training (pretty high volume bodybuilding program).

Yea…I am not signing up to have my testosterone floored to less than a tenth of what it was, BUT interestingly, these untrained (20ish% body fat) dudes still saw lean muscle mass gains even with testosterone smashed at or below 50 ng/dL and they also showed the same improvement in 10RMs as the group that had un altered testosterone concentrations that held in the mid-physiologic range.

The suppressed testosterone group did gain fat while the placebo lost fat, but we cannot conclusively say that this was all the result of testosterone, as estrogen, thyroid, and energy balance all come into play (this study did not have any dietary controls in place which is a huge red flag when looking at the body comp data). However, the seminal data from Bhasin et al. (without a resistance training arm) showed similar increases in body fat changes at the lower doses of testosterone while combined muscle loss (Data Below) which looked to be not only attenuated, but increased by resistance training in the current study.

Kvorning et al. also analyzed satellite cell number in these subjects and BOTH groups significantly increased their satellite cell pool with no significant differences between groups.

However, only the placebo group showed a significant increase in myonuclear number in Type II fibers with no change in either group for type 1 fibers.

It is very interesting to read both of these papers because they are written in very a positive light towards testosterone, when the findings are in fact somewhat lackluster, and definitely not blow out wins especially inside of physiologic ranges.

If you put this together with the research on hypertrophy rates and hypertrophy potential of males vs. females it doesn’t really appear that changes in testosterone within the physiologic range have that big of an effect size on the ability to put on muscle at least in untrained subjects. We also do not know if this effect is independently additive (1+1=2) or synergistic (1+1=10). I would guess IF there is a synergistic effect on muscle hypertrophy between testosterone and resistance training it lies in myonuclear potential and the increase in the ceiling of which someone can hit, BUT we still need more research. And we desperately need research in trained subjects where all these annoyingly meticulous details likely have a more pronounced effect in wringing out the last percentage points of one’s genetic potential.

Until then LIFT because regardless of your gender, age, or sex hormone status it just WORKS. And with an estimated 91% of Americans being overfat and severely under-muscled we evidently have a lot of WORK to do.

References:

  1. Bellamy LM, Joanisse S, Grubb A, et al. The acute satellite cell response and skeletal muscle hypertrophy following resistance training. PLoS One. 2014;9(10):e109739.
  2. Egner IM, Bruusgaard JC, Eftestol E, Gundersen K. A cellular memory mechanism aids overload hypertrophy in muscle long after an episodic exposure to anabolic steroids. J Physiol. 2013;591(24):6221-6230.
  3. Kvorning T, Andersen M, Brixen K, Madsen K. Suppression of endogenous testosterone production attenuates the response to strength training: a randomized, placebo-controlled, and blinded intervention study. Am J Physiol Endocrinol Metab. 2006;291(6):E1325-1332.
  4. Kvorning T, Kadi F, Schjerling P, et al. The activity of satellite cells and myonuclei following 8 weeks of strength training in young men with suppressed testosterone levels. Acta Physiol (Oxf). 2015;213(3):676-687.
  5. MacKrell JG, Yaden BC, Bullock H, et al. Molecular targets of androgen signaling that characterize skeletal muscle recovery and regeneration. Nucl Recept Signal. 2015;13:e005.
  6. Murach KA, Englund DA, Dupont-Versteegden EE, McCarthy JJ, Peterson CA. Myonuclear Domain Flexibility Challenges Rigid Assumptions on Satellite Cell Contribution to Skeletal Muscle Fiber Hypertrophy. Frontiers in physiology. 2018;9:635.
  7. Schwartz LM. Muscle nuclei remember to cheat death. J Physiol. 2013;591(24):6133-6134.
  8. Serra C, Tangherlini F, Rudy S, et al. Testosterone improves the regeneration of old and young mouse skeletal muscle. The journals of gerontology Series A, Biological sciences and medical sciences. 2013;68(1):17-26.
  9. Sinha-Hikim I, Roth SM, Lee MI, Bhasin S. Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Am J Physiol Endocrinol Metab. 2003;285(1):E197-205.
  10. Thorley M, Malatras A, Duddy W, et al. Changes in Communication between Muscle Stem Cells and their Environment with Aging. J Neuromuscul Dis. 2015;2(3):205-217.
  11. Yu JG, Bonnerud P, Eriksson A, Stal PS, Tegner Y, Malm C. Effects of long term supplementation of anabolic androgen steroids on human skeletal muscle. PLoS One. 2014;9(9):e105330.
  12. Zeng F, Zhao H, Liao J. Androgen interacts with exercise through the mTOR pathway to induce skeletal muscle hypertrophy. Biol Sport. 2017;34(4):313-321.