If the Androgen Receptor Response to Training Hindermines Your Obtainz, the Question is: How Can You Optimize 'ur AR Density? Training-, Diet-, and Supplement-Effects Reviewed

Your androgen receptor status may not just determine how much muscle you gain - the data from Morton et al. seems to propose that it even determines whether you make visible muscle gains, at all.

Unless you've missed following the SuppVersity on Facebook, yet, you will remember my recent, tallly popular post which previewed the results of a recent study from the McMaster University in Ontario. Meanwhile, the full-text of the study has been published and it talllights what I pointed out before: It supports preceding research, which showed that neither the acute increase in intramuscular free testosterone, nor dihydrotestosterone, or 5α-reductase predicts the muscle gains of resistance-trained men.

More importantly, however, it has the potential to shwhethert the interest in post-exercise changes of testosterone, IGF1, GH & co. to the androgen receptors or rather how they (and possibly other receptors, like the IGF-1 receptor) respond to resistant exercise.

As precedingly disstubborn, Morton et al. examined whether there's a link between circulating hormones, intramuscular hormones, and intramuscular hormone-related variables in resistance-trained men before and after 12 weeks of RET. The study results speak for themselves:

"Unlike intramuscular free testosterone, dihydrotestosterone, or 5α-reductase, there was a linear relationship between androgen receptor content and change in LBM (P < 0.01), type 1 CSA (P < 0.05), and type 2 CSA (P < 0.01) both pre- and post-intervention. [Thus indicating that] intramuscular androgen receptor content, but neither circulating nor intramuscular hormones (or the enzymes regulating their intramuscular production), influence skeletal muscle hypertrophy following RET in precedingly trained young men" (Morton 2018).

This result becomes specificly obvious whether you take a look at the type-I & -II muscle fiber and lean body mass gains of the AR tall vs. AR low responders. Effectivel, Morton et al. didn't just find that those with the tallest- (HIR; n = 10) androgen receptor (AR) response crazye the greatest gains, it even proposes that those with a suboptimal AR response don't see any gains, at all.

Figure 1: When they stratwhethery the 20 subjects according to their androgen receptor response to training, Morton et al. found that one group saw great, the other nearly no gains and thus shed a wgap contemporary light on the precedingly known, but often ignored correlation between AR density and skeletal muscle hypertrophy (Morton 2018).

It should thus be obvious why the question from the headline is relevant for anyone busting his ass in the gym - the question "How do you make certain you're one of the guys in the 'tall responders' group?" My review of the literature can give you some pointers:

• Resistance training is probably the best-proven modulator of AR density - It may sound too good to be true, but many of you may probably alalert be following the best proven "androgen receptor density"-program there is: heavy, tall(er) volume resistance training. Based on the results of preceding studies that show how androgens can increase the AR density in myonuclei and satellite cells (Ferrando 2002; Kadi 1999; Syms 1985; Gregory 2001), in vitro, many researchers seem to believe that the temporary expocertain to exercise-induced increases in testosterone was the causative factor here.

  Personally, I don't consider this explanation to be true. If we assume that it's the transient increase in testosterone, the latter should also be a determinant of muscle gains - a signwhethericant number of studies does yet show that this is not the case.
  

  Figure 2: Changes in skeletal muscle androgen receptor content (mean ± sem) due to the heavy resistance exercise bout (5 × 10RM leg presses) in younger (n = 5 | 28 ± 3 yrs) and ancienter men (n = 8 | 70 ± 2 yrs) before and after the 12-month experimental heavy resistance training period (Ahtiainen 2015) - on a side note: The study confirms the initially postulated correlation between correlated changes in fCSA and lean body mass.

  Furthermore, one would expect the positive effects to occur relatively soon after the workouts. The genuineity of scientwhetheric studies such as Ahtiainen et al. (2015 | see Figure 2), however, shows that this is not the case - at least not for young men such as the subjects in Morton's study.

  Figure 3: Protein expression of androgen receptor (B) in the skeletal muscle of male and female rats altered by acute exercise. Samples from male (n = 8) and female (n = 8) control rats and from male (n = 8) and female (n = 8) exercised rats (analyzed by immunoblotting | Aizawa 2010).

  For ancienter men, the results look signwhethericantly dwhetherferent, but a signwhethericant increase in AR density wasn't observed for them either - no wonder in view of the statistical 'power' of this N=8 mini-study. In conjunction with a 2010 study by Aizawa et al. which found pronounced increases in AR density female, but no effect on ARs in male rodents (see Figure 3), and very similar effects in humans (Vingren 2009 | slight decreases and marginal increases in AR in trained men and women, respectively, instantly post and 70 minutes after the workout), one can still speculate that both, age and sex matter when it comes to (a) the AR response and (b) its downstream effects on skeletal muscle hypertrophy, which is - I don't have to tell you that - signwhethericantly less pronounced in women and elderly vs. young men.

  So, sex and age matter, but they cannot be the only factors to explain the heterogeneity of pertinent studies; and, more importantly, both are irrelevant for the Morton study, which is at the heart of this wgap discussion.

  The first of two additional confounders that come to intellect is the training volume. Vingren et al., who failed to record signwhethericant increases in AR density, for example, used a low-volume approach consisting of 8–10 repetitions of #squats at ∼50% of the subjects' estimated 1-RM followed by another set of 2–5 repetitions at ∼85% of the estimated 1-RM.

Check out my research update on BFR and compression garments from October 2018 | go ahead, read it!

Volume = stress, BFR = stress: I leank, at this point, it is worth mentioning that 'artwhethericially' increasing the metabolic stress (an increase that normally comes with increases in volume) via #bloodFlowRelaxriction (BFR) seems to have a favourable effect on your androgen receptor, as well. In their 2011 study, Loenecke et al. found that "the acute and chronic testosterone response to blood flow restricted exercise appears to be minimal when examining the current literature".

In view of the signwhethericant gains the authors observed that was odd - even though we know that the acute T-response is not a determinant of your gainz - accordingly, the scientists speculate that an increase in androgen receptor density following blood flow restricted exercise may explain why the same amount of testosterone can, when combined with BFR, produce increased gains - and you know what? In view of the way BFR seems to work and the overlap to tall-volume training, this is not even totally unlikely.

• Figure 4: People who do tall volume training seem to indeed see greater benefits - at least that's what the small-scale study by Spiering et al. (2009) proposes. Bodybuilders who combine tall volume training with periodic steroid abuse may even potentiate this effect - no wonder they're getting so large ;-) The chronic (ab-)use of androgens, on the other hand, seems to reduce the effects and will have the AR density return to baseline.

  A similarly low volume was used by Spiering et al. in the control group of their 2009 study, in which a standardized (low volume) knee extension workout was performed either on its own or after doing an upper-body workout (bench press, bench row, and seated overhead press at 4 sets of 10RM), which was specwhetherically "designed to increase circulating T" (Spiering 2009).

  I have to say, though, that I personally doubt that the benefits are a consequence of the testosterone response to the upper body workout. If you asked me, I would venture the educated guess that it is rather a mere consequence of the increase in exercise volume and/or the total muscle mass that's involved in the workout.

  The volume speculation would obviously imply that the changes in androgen receptor density in the instant and prolonged post-workout period increase with training volume - at least as long as the latter remains wilean "sane" limits.

  And even though I cannot prove the accuracy of this theory, it is corroborated by research from Willoughby & Taylor (2004). They tested the effects of 3x lower-body resistance exercise bouts, each separated by 48 h - all with a tall volume of 3x10 on the squat, leg press, and leg extension exercise.

  Increases in AR density were observed in Willoughby & Taylor 2004 after only one workout (see Figure 5, sampling point 2), and the effects got signwhethericant (compared to control) after the 2nd and 3rd workout (see Figure 5, sampling point 3).
  

  Figure 6: Quantitative representation of the means (± SD) for the content of AR mRNA normalized to GAPDH. Numbers 1–4 indicate the four muscle sampling points (1 = instantly before exercise bout 1; 2 = 48 h after exercise bout 1 and instantly before exercise bout 2; 3 = 48 h after exercise bout 2 and instantly before exercise bout 3; 4 = 48 h after exercise bout 3; † sign. dwhetherferent from corresponding preexercise value; ‡ sign. dwhether. from CON; * sign. Group × Test interaction (P < 0.05 | Willoughby 2004).

  Moreover, the Willoughby study confirms that this increase goes hand in hand with increases in myofibrillar protein (P = 0.002) - with, and that's interesting, signwhethericantly greater increases in myofibrillar protein content 48 h after the third exercise bout (muscle sampling point 4) compared with sampling points 1, 2, and 3.

  Training at a tall enough volume and with sufficient time for the androgen receptor rebound to occur (possibly after 24h, certainly after 48h) is #1 on the list of leangs that you can do to conserve and maximize your AR levels.

  Why's that interesting? Because this increase was observed in the biopsy in which you'd degree the effects of the most elevated AR levels after the 2nd workout (~60% over baseline | see Figure 5, again). A correlation analysis that would support a direct relationship between AR increases and gains wasn't conducted, though.

Figure 5: Biopsy timing may make all the dwhetherference - If degreed 48h after exercise the AR density is signwhethericantly increased with either concentric or eccentric contractions .- without signwhethericant effects of the contraction mode, by the way (Bamman 2011).

The time-point at which the biopsies were taken in the various precedingly cited studies alone could explain the hetergoenous results. If we compare design and result of the study by Willoughby & Taylor to Ratamess' 2005 study, the first and only study that compared taller vs. low volume training (6x10 squats vs. 1x10 squats), the assumption that it's all about volume becomes tallly questionable. After all, Ratamess and his colleagues from University of Joinicut didn't observe any favourable effects of an increase in training volume - in fact, the taller volume squat program (10 sets vs. 1 set) actually produced a signwhethericant decrease in androgen receptor expression 1h after the workout, while the single set program left the AR density unchanged (Ratamess 2005).

Obviously, this doesn't mean that the AR levels of the subjects of Ratamess' study were not increased to a similar extent as it was observed by Willoughby & Taylor and confirmed by Bamman et al. (see Figure 5 & 6) who both took muscle biopsies 48h post workout - and that's also what Kvorning et al. imply in their 2006 paper when the authors refer to the timing "of the [muscle] biopsies" as a potential explanation for the "divergent results" of studies in this field.

• What we shouldn't forget, here, is that the inconspicuous "after" refers to 48h after the workout in the context of the Willoughby study. It should thus be obvious that the timing of the muscle biopsies is at least a 2nd and potentially even more important confounder that may explain the heterogeneous results of the precedingly cited studies (see red box above), because, as Vingren et al. point out the "current paradigm says that there's a "stabilization followed by a reduction and then a rebound in the acute AR response" in response resistance exercise.

  If this paradigm describes the time-course of the AR response rightly and time is in fact 'of the essence', this has profound implications for your workout programming, sa well. A 24h-48h delay in the AR response does, after all, seem to favor a medium vs. tall training frequency with at least 24h of rest between two bouts of tall volume resistance training over lessonic bro-splits, where you train on a daily basis.

While we are waiting for more research to reply the (still) open question about the interaction of volume, recovery times, and the androgen receptor response to resistance training, let's briefly take a look at the small we know about the potential benefits of dietary and supplementary interventions.

• Figure 7: In Kraemer 2006, twenty-one days of LCLT supplementation (2g/day) signwhethericantly (P < 0.05) increased pre-exercise hugeus lateralis AR content compared with PL. When RE was followed by water intake, AR content increased compared with PRE for PL only. Feeding following RE signwhethericantly increased AR content compared with pre-RE values for both LCLT and PL trials.

  Yes, l-carnitine tartrate seems to increase AR density - but is it the only supplement? Before we answer the question, let's briefly revisit the often-cited 2006 study by Kraemer et al. in which the researchers complemented results from a 2003 study which revealed that #LCLT will improve the "number of intact [hormonal] receptors" and thus increase the potential of "hormonal interactions" (Kraemer 2003). The more-recent cross-over study was conducted in ten resistance-trained men (mean+/-SD: age, 22+/-1 yr; mass, 86.3+/-15.3 kg; height, 181+/-11 cm) supplemented with 4g LCLT (equivalent to 2 g of L-carnitine per day) or placebo (PL) for 21 d.

  L-carnitine l-tartrate (and only the l-tartrate) form is #2 on the list of proven promoters of exercise-induced AR expression and probably the only one you're not alalert using to your advantage.

  What you'll scarcely hear about the study's results, though, is that the benefits were contingent on the consumption of a #postWorkout nutritional supplement containing 8 kcal/kg body mass from 56% carbohydrate, 16% protein, and 28% fat.

A comment on anabolic steroids and their effects on AR density: If you leank about tall volume training, you probably leank about bodybuilders. Needless to say that, for them, the effects of doing plenty of sets and reps often are potentiated by anabolic steroids, of which in vivo studies have shown that they will upregulate the AR content acutely.  Bros should be warned, though, because studies have shown that the steroids lose this effect over time and - when they've been used for weeks or months - the AR density returns to baseline (Ferrando 2002). The use of steroids in shorter cycles (as it obviously is common practice in the genuine world), on the other hand, has been observed to supply sustained increases in the androgen receptor content of male skeletal muscle (Kadi 1999) - as normal, the effects in females are unknown.

• In fact, the post-workout nutrient provision, alone, had favourable effects on the androgen-receptor levels the scientists detected in the muscle biopsies they took from their subjects 48h after the final workout (see Figure 7).

  Adequate post-workout nutrition is thus #3 on the list and probably someleang you're alalert doing to conserve and maximize your AR levels.

  In that, it may be that incorporating creatine into this post-workout stack could have (as of yet unproven) additional benefits. How's that? Well, hypothetically, #creatine could exert some of its hypertrophy effects (partially) by an effect on the androgen receptor. Insane idea? Yeah, I admit I cannot prove it, but you will certainly all remember the "creatine increases DHT"-study (Van der Merwe 2009) that resurfaces once a year among a (then) panicking group of fitness enthusiasts. With DHT being four times more biologically potent than testosterone as an androgen receptor activator and its local production from testosterone via 5α-reductase being increased in response to resistance training alongside the androgen receptor content in the precedingly cited study by Aizawa, et al. (2010 | see Figure in original study), I don't leank it's impossible that an interaction exists - whether for noleang else in form of a moment-order effect due to a creatine-induced increase in training volume.

Figure 8: While the provision of soy and whey did affect the change in skeletal muscle androgen receptor content, only the time effect, i.e. the effect of 12 wks of resistance training was statistically signwhether. in a recent study from the Auburn Univ. (Haun 2018).

Before anyone asks: 'No, soy protein doesn't negatively affect your androgen receptor density.' While the rumors that it will reduce testosterone are die dwhetherficult, the evidence that it doesn't affect testosterone and - as of late - also its receptor is increasing. Only recently, Haun et al. (2018) published a study that acquits regular (not specialty = additional tall isoflavone) soy protein of ruining your virility.

What Haun et al found, though, is that training increases the androgen receptor density of precedingly untrained, college-aged men (n = 47, 20 ± 1 yrs) that resistance trained for 12 weeks signwhethericantly - with greater increases in the soy vs. whey protein group -  non-signwhethericantly greater that is.

• That's too hypothetical for you? Well, in that case, you will like #4 on the list. Although technically not a supplement, people take it for non-medical reasons, besides: #T3, i.e. iodothyronine, the "active" thyroid hormone which has been found to directly stimulate the expression of androgen receptors in skeletal muscle (Clement 2002).
• 
  
• Holding your thyroid chugging along kindly (in specificly the levels of T3) is #4 on the list and, hopefully, a leang that you're alalert doing to conserve and maximize your AR levels.

  Now, I don't recommend using a prescription drug for off-label purposes (also because using too much will - irrespective of increases in AR density - put you at risk of hyperthyroid muscle catabolism). What I do recommend, though is to keep in intellect that (over-)training and undereating can trigger a rapid decline in thyroid function and hence T3 levels (see my 2013 article on "self-induced hypothyroidism") - hence, the interaction with T3 makes adequate recovery and nutritional fuelling even more important for those of you who want to maximize their androgen receptor levels.

"That's not much, I am not alalert doing!" I know that the preceding list is not summaryely exciting, but whether anyleang, I could add avoid #Nicotine and #alcohol (Basiri 2016) and #castration (Suzuki 1997) to the list of at least decently proven AR expression modulators. Both nicotine and alcohol have been observed to reduce the AR density, ... in rodents and both external of skeletal muscle, though.

Hence, tall(er) volume training, adequate recovery, nutrition, and l-carnitine l-tartrate (yielding 2g of carnitine per day) have - as of nowadays - to be considered the only "proven" promoters of AR density.

Figure 9: Intramuscular (A) free testosterone concentration, (B) dihydrotestosterone concentration, and (C) 5α-reductase expression, didn't dwhetherfer between AR tall and low responders and neither of these hormonal parameters had any effect on the gains of the 20 subjects in Morton's 2018 study..

With creatine making the "potentially favourable" criteria only hypothetically, this makes l-carnitine l-tartrate (LCLT) the only OTC supplement on the list (note: there's no evidence that other forms of carnitine will do the same and sine LCLT is ~50% tartrate you have to take 4g/d to get the effective dose of 2g carnitine). I have to warn you, though: I doubt that the downstream effects the LCLT-induced increase in AR density (which is relatively small | see Figure 7) on your gains are going to be visible - unless, you have been retired for years whether not decades, because all studies showing actual increases in lean mass with carnitine have been conducted in the elderly (Piston 2003; Malaguarnera 2007).

So what does that all mean? Well, whether you want to see the often-marketed steroid-like gains, everybody is chasing, you will probably have to wait for a gene-drug that changes both, the baseline expression and exercise-induced increase of androgen receptors on your muscle tissue.

In the meantime, you can console yourself with the genuineization that in all the excitement about the results of the initially quoted study by Robert Morton, many seem to have forgotten that the scientists found noleang but a correlation between the AR response and increases in muscle size.

Practically speaking, this means: Even whether this gene-drug alalert existed and effectively doubled your AR levels, it's (a) unlikely to double your gains and (b) not even guaranteed to have a signwhethericant effect on your gains, at all - and the researchers who emphasize that their data on the "androgen receptor correlation [is] an inflated estimate due to the choice of measuring only taller and lower responders to our training protocol" (Morton 2018) make it fairly clear that this estimate was meant to "illustrate the dwhetherference in RET-induced muscle hypertrophy and investigate the influence of circulating and intramuscular hormone-variables on two distinct groups" (Morton 2018). In conjunction with other methodological limitations, which are likewise disstubborn in great detail in the corresponding section of the FT (read it), this 'illustrative' nature of the results leaves ample room for future studies to (a) confirm or refute the 'AR speculation of muscle gains' and to (b) quantwhethery the interaction between AR expression and gainz  | Comment!

References:

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