Anabolic Workouts Revisited - Testosterone, GH, Prolactin & Co: Differential Effects of Workout Type, Volume, Density

Ronnie Coleman is just one of the pros who trained with crazily high volume and weights - is that the way to go, or does it require too many "supplements"?
"What's the most anabolic form of training?" To answer that question we would actually have to initially define how we are planning to measure "anabolism". If we go by the more or less confuted paradigm that the immediate hormonal response to a workout is one, if not the, fundamental determinant of it's effectiveness, today's blogpost provides you with a whole host of already known and novel insights that could come handy, when you're setting up your next workout routine.

Please keep in mind, though, that the study by West et al., in which the researchers found no correlation between exercise induced increases in testosterone and only weak correlations between growth hormone and fast twitch muscle fiber size and cortisol and overall lean mass, over a 15-week period, as well as my dissertations on the complexity of "building muscle" in the Intermittent Thoughts on Building Muscle, while I am taking you through the latest results.

Part I - Shorter rest times = greater "anabolism"

I'd like to start out with the results,Villaneuva et al. recently published in the Journal of Strength and Conditioning Research (Villanueva. 2012). The scientists from the University of Southern California conducted a 2x2 randomized trial involving strength and hypertrophy oriented total body workouts on Tuff Stuff Performance Series equipment with different different set/rep schemes and rest times, but identical exercises for both:
  1. maximum strength protocol (S)
    8 x 3 (sets x reps) at 85% of predetermined 1-RM for all resistance training exercises; 60 seconds (S60) or 90 seconds (S90) rest in-between sets
  2. muscular hypertrophy protocol (H)
    3 x 10 (sets x reps) at 70% 1-RM for all resistance training exercises; : performed with either 60 seconds (H60) or 90 seconds (H90) rest in-between sets 
  • smith machine barbell back squat
  • flat barbell bench press 
  • narrow/neutral grip lat pulldown 
  • seated unilateral knee extension
The six study participants were young men, who volunteered for the study (age 26+/-2.4 years, 178.6 +/-5.9 cm, and 86.4+/-1.2kg) were healthy and described as "recreational resistance trainees who trained at least 2 days per week (>2 years)" (Villanueva. 2012).None of them was yet a competitive weight lifters or did engaged in any other sport-specific training. Furthermore none of the 6 participants took any medication or dietary supplements that could potentially have skewed the results, i.e. the change in cortisol and total testosterone levels, I plotted in figure 1:
Figure 1: Change of total serum testosterone concentration from rest (PRE) to immediately post-exercise (POST), Pre to 15 minutes post-exercise (15 MIN), and Pre to 30 minutes post-exercise (30 MIN) for strength and hypertrophy protocols with short (60s) and "long" (90s) rest period (* indicates significant difference - p < 0.05; based on Viallaneuva. 2012).
The overall message here should be clear: If you want to ramp up your testosterone levels, hit it fast and in the classic hypertrophy range with 3 sets of 10 reps!

Exercise-induced increase in testosterone = anabolism?

While we cannot exclude that the exercise induced increase in testosterone (and other "anabolic" hormones) is a necessary and facilitative part of the adaptive cascade at the end of which you may in fact have gained another inch on your arm, the results of the initially mentioned study from Phillips lab at the McMaster University in Ontario, do at least suggest that there is no linear, nor otherwise proportional relationship between exercise induced increases in testosterone and gains in lean muscle mass (West. 2012).
Figure 2: Differential endocrine response to high vs. low volume squatting in healthy trained men - androgen receptor content of vastus lateralis (left), total testosterone levels (right; data based on Rattames. 2005)
The notion that intracrine (=within the cells) processes, proteins and hormones are the actual driving forces and controlling factors in skeletal muscle growth is further supported by observations Ratamess et al. made in 2005. The researchers from the Human Performance Laboratory at the University of Connecticut found a 45% reduction in androgen receptor expression in response to high (figure 2, MS: 6x10, 2min rest in-between) vs. low volume (figure 2, SS: 1x10) squatting sessions in healthy, resistance-trained men with a minimum 3 years of experience with the back squat exercise. At first sight, this does certainly seem as if the testosterone response was pretty useless, after all, even this proven muscle builder (see "Zoning In On the Big T" and "Quantifying The Big T") cannot do its muscle building job, if there is no receptor to bind to, right?  Correct! ... but follow up studies by Spiering et al. and Vingren et al. have shown that the testosterone release in and out of itself will illicit increases in receptor density which do however need some time to take place: In that, the +14% increase in testosterone in response to a high volume upper body workout in the Spiering study increased the androgen receptor expression 3h after the workout by 40% over control (Spiering. 2009).

Strength vs. Hypertrophy - Check... Endurance exercise & Sprinting?

Before we discuss the implications of these findings, let's briefly take a look at another even more recent study trying to discover the complicated hormonal response to different types of exercise that could help us to grasp a better notion of "The latest on working out for anabolism". Now, I would venture the guess that 99% of you are probably thinking about "3,2,1" vs. "5x5" vs. "HST" and a couple of other classic strength training or bodybuilding routines, right now. The results the already mentioned study which have been published only 4 days ago in the Journal of Applied Physiology do yet bring two unexpected training types to the play: Sprinting and endurance training. I see, you are surprised. Well, at least for the first one, i.e. sprinting, you actually should not be; after all, I have been writing about the protein anabolic effects of HIIT (=multiple sprints) before (see "The Anabolic Effects of HIIT"). So, if it increases muscle protein synthesis by >40%, why shouldn't sprinting also be able to establish an overall more anabolic milieu? But endurance training?
Figure 3: Prolactin, insulin (in the absence of a "control" AUC, I calculated the value relative to the mean), testosterone, cortisol and growth hormone (GH) area under the curve (pre to 60min post) in 8 healthy young men in response to 4 separate trials involving resting (control, relative to which all the other values - except insulin - are expressed to), resistance training, sprinting and endurance training (for details see text; data based on Stokes. 2012)
Yeah, it sound counterintuitive, but if you take a close enough look at the data in figure 3 and take into account growth hormone (GH) bars at the right hand side of the colored graph have their own scale you will have to concede that the 8.4x increase in growth hormone expression in response to 30min cycling at 70% of the VO2max are pretty impressive. Specifically, if you consider that the competition, i.e. a...
*the scientists write it the other way around, but honestly I have not et come across a study, where the rest between sets was longer than the one between exercises, so I assume this is a typo
  • 30min total-body resistance training regimen - bench press, leg press, bench pull; 75% 1RM 5 sets 10 reps, each; 60s rest* between sets, 180s rest* between exercises, and an
  • all out 30s sprint that was performed subsequent to a warm-up that consisted of cycling for 4 min at 60 W, 30 s at 80 W, and
    then 30 s at 100 W and a 5-min pause on a friction-loaded cycle ergometer at 7.5 % (75 N/kN) of the subject’s body mass
were training regimen you would probably rather associate with the term "growth" as in "growth hormone". Now, if you ask the "bros" about their reasons for taking GH, I guess that few of them will still be falling for the idea that it was a great muscle builder (when used appropriately, it can be a exponentiate the anabolic effects of superphysiological doses of testosterone, though).

Most of them will probably tell you that it helps you lean out... and why does it do that? Simply because it helps with fatty acid mobilization and oxidation. And when is the need for the latter the greatest? When you sleep, yeah... when you fast, ok... but also when you expend huge amounts of energy from fat! And that's exactly what's happening during the 30min of cycling at 70% of the VO2 max, an undertaking that does not simply burn relatively, but most importantly absolutely significantly more energy and thus fat, than either the strength training (82% less energy expenditure) session, or the sprint session (94% less energy expenditure).

Fine, so a drop in FFA will increase GH, but what's that about prolactin?

Figure 4: GH response of young men in response to exhaustive endurance (15min, targer HR 160bpm) and resistance training (total-body, 5 exercises, 4 sets classic pyramid, 1-2min rest) and combined training (crossfit-style + 6x10m sprints) from Akbari. 2012
These remarks on growth hormone do yet not answer a question of which I suppose that it's already preying on your minds: What's that about sprinting induced increases in prolactin? Well, if
  • higher volume weight lifting in the hypertrophy range (8-12 reps) increases testosterone, and
  • energy consuming endurance exercises with a tendency to reduce free fatty acids in the purported "fat burning zone" (70% VO2Max) increases GH
the straight forward answer to this question would be: A ...
  • higher mean work rate [=energy expenditure per time unit of exercise] maintained only over a very short timespan increases prolactin
And just to make that clear, the work rate during the sprint was 430% higher than during the resistance training session and still 260% greater than during the 30min of cycling.

On a side note: The drop in insulin after the endurance trial (>60% immediately post) supports the view that the associated GH response is primarily fat-catabolic and not muscle anabolic. Moreover, it's IGF-1 it's splice variants MGF & Co, not it's parent GH which are mainly responsible for the muscle building effect. And at least the synthesis of IGF-1 is in a hitherto not fully elucidated way related to insulin (click here to learn more), the villain of the last decade that was once, and is still hailed among many hardcore bodybuilders as "the most anabolic hormone of all"!
In view of the fact that this rise in prolactin (actually somewhat of an acute stress response, of which we don't yet know what exactly it's role wrt to training adaptation is) went hand in hand with a temporary increase in insulin this may sound as if sprinting was a bad thing, but the spike in insulin may have been significant compared to the steady insulin levels of the control, let alone the declining insulin levels in the endurance trials, but was almost identical to the one that occurred in response to the resistance training regimen (the AUC for insulin was even higher in the 60min after the resistance training protocol). And has, as Stokes et al. point out unquestionable benefits:
"Increased insulin concentrations as seen following the sprint trial [...] might facilitate muscle glycogen synthesis during recovery through insulin’s actions on both glucose transport and on glycogen synthase activity. The significant increase in insulin concentrations following sprint exercise in the present study is followed by a suppression of blood glucose concentrations to levels below pre-exercise. This finding might have implications for individuals who have difficulty regulating blood glucose concentrations, such as individuals with impaired glucose tolerance." (Stokes. 2012; my emphases)
The post-exercise increase in the universally and wrongfully demonized insulin could thus not just come handy for the the 8 young recreationally active men who participated in the study at hand, but also for the average and extraordinary gymrat (like yourself?) and even the obese type II diabetic who has finally found his/her way to physical culture! And this is not simply a vague assumption, but an already empirically validated hypothesis (e.g. Richards. 2010; Whyte. 2010).

So what does all this tell us then?

Did we even answer our question? By now you should actually notice something. The question "What's the most anabolic workout?" cannot be answered with only one definition of "anabolism" on your mind. The classic body part split with 3-5 sets of 5-10 reps per exercise is probably still the way to go, if your perspective on anabolism relates to increased skeletal muscle hypertrophy based on both, endocrine (testosterone), as well as intracrine (mTOR) responses to your workouts. If you want to build your brain and thus interpret "anabolism" as "neurogenesis", you will have to either sprint or do extra-long endurance work (Rojas Vega. 2012) or have lot's of sex to up your prolactin levels . And if your mitochondrial density is what's on your mind, when you think of "anabolism", HIT and HIIT should be your best friends.
Aside from the time-delayed increase in testosterone receptor expression, of which you could either argue that it could be evidence for a shift from an intracrine to an endocrine anabolic response, and the beneficial effects of an increase in insulin at the right time, namely post-workout when your muscles are ready to take up the glucose that could otherwise end up being converted to triglycerides and stored in one of the numerous fat depots of your body, there are two other imho important reasons not to simply fall into the opposite extreme and say "Wtf if exercise induced increases in anabolic hormones don't correlate with muscle growth they are completely worthless!":
  1. Real world, not lab evidence: High(er) volume training with short(er) rest periods was and still is the way the majority of using and non-using athletes are "building" those physiques on, people actually have on their minds, when they are looking for the "most anabolic workout"
  2. Effects on intracrine factors of anabolism: From mTOR-dependent local protein synthetic response over the many, hitherto not fully understood intracrine growth factors, the role and function of inflammatory cytokines and the immune response to exercise, up to the maintenance and incorporation of satellite cells into new myonuclei and the PGC1-alpha driven increase in mitochondrial density, all of the things, we are training for show some correspondence with the exercise induced systemic expression of "anabolic" or "catabolic" hormones.
The main problem is therefore, as Stokes et al. state, that we still have an "over-simplistic" concept of the "anabolic (e.g. testosterone and growth hormone) and catabolic (e.g. cortisol) hormones" (Stokes. 2012), in which things like the prolactin response to exercise, which has only recently been implicated as a driving force of exercise induced neurogenesis (Rojas Vega. 2012), have not even had a place, until now... apropos prolactin, you should be aware that having an orgasm will likewise elicit a temporary spike in prolactin levels and sex is therefore "brain-o-bolic" (see my post on the matter on the SuppVersity Facebook wall)!

  • Akbari A, Mojtahedi H, Marandi SM, Movahedi A, Ramsheh SFR. Comparing the Effects of Three Types of Exercise (Exhaustive Endurance, Intensive Resistance and Combined Exercise) on the Secretion of Growth Hormone in Active Men. World Journal of Sport Sciences. 2012; 6 (3): 247-253. 
  • Ratamess NA, Kraemer WJ, Volek JS, Maresh CM, Vanheest JL, Sharman MJ, Rubin MR, French DN, Vescovi JD, Silvestre R, Hatfield DL, Fleck SJ, Deschenes MR. Androgen receptor content following heavy resistance exercise in men. J Steroid Biochem Mol Biol. 2005 Jan;93(1):35-42.
  • Richards JC, Johnson TK, Kuzma JN, Lonac MC, Schweder MM, Voyles WF, Bell C. Short-term sprint interval training increases insulin sensitivity in healthy adults but does not affect the thermogenic response to beta-adrenergic stimulation. J Phys-iol (Lond). 2010; 588(15):2961–2972 
  • Rojas Vega S, Hollmann W, Struder HK. Influences of exercise and training on the circulating concentration of prolactin in humans. J Neuroendocrino. 2012; 24(3):395–402.
  • Spiering BA, Kraemer WJ, Vingren JL, Ratamess NA, Anderson JM, Armstrong LE, Nindl BC, Volek JS, H√§kkinen K, Maresh CM. Elevated endogenous testosterone concentrations potentiate muscle androgen receptor responses to resistance exercise. J Steroid Biochem Mol Biol. 2009 Apr;114(3-5):195-9.
  • Stokes KA, Gilbert KL, Hall GM, Andrews RC, Thompson D. Different responses of selected hormones to three types of exercise in young men. Eur J Appl Physiol. 2012 Sep 13.
  • Villanueva MG, Villanueva MG, Lane CJ, Schroeder ET. Influence of Rest Interval Length on Acute Testosterone and Cortisol Responses to Volume-Load Equated Total Body Hypertrophic and Strength Protocols. J Strength Cond Res. 2012 Jul 12. 
  • West DW, Phillips SM. Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training. Eur J Appl Physiol. 2012 Jul;112(7):2693-702. 
  • Whyte LJ, Gill JMR, Cathcart AJ. Effect of 2 weeks of sprint interval training on health-related outcomes in sedentary over-weight/obese men. Metabol Clin Exp. 2010; 59(10):1421–1428.
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