Sunday, May 19, 2013

How To Build Muscle

Today we're talking about the best ways to maximize muscle growth (skeletal muscle hypertrophy).

In the primer, we established a few rough parameters that can be improved through strength training.  To recap, they include hypertrophy (muscle size), neural adaptation (efficiency), and strength-skill improvement (getting better at a particular movement).  There's plenty more that strength training can improve, but those are our points of interest.

Right now you might be thinking that the subject of building big muscles has been done to death.  Humor me and read through it, because I'd put money down that you aren't squeezing every drop of growth out of your training program.

*please note that the following article is dedicated entirely to muscle size, thus any training recommendations will be made in a vacuum where the only thing the trainee cares about is packing on muscle.

What Is Hypertrophy?
Muscular hypertrophy is the growth of either muscle mass, cross-sectional area, or both.  Simple enough, right?  Something worth mentioning is that not all hypertrophy is of the same quality.  You'll often see discussions on the difference between myofibrillar and sarcoplasmic hypertrophy, with some protocols claiming a chance of spurring the elusive hyperplasia.  The debate between big versus strong, or functional versus non functional muscle size has been raging for decades.

In real life, hypertrophy is never so compartmentalized.  Size can come from synthesis and addition of new contractile proteins, stuffing in more glycogen/sarcoplasm, water retention from certain supplements, and so on.  Personally, I don't think it's worth worrying about.  I've found that the only people who ever truly guilty of being massively big yet laughably weak are those who forego any semblance of functional training and/or are roided up to to their eyeballs (usually they go hand in hand).

How Hypertrophy Works
Let's say you live with your girlfriend in a two bedroom house (if you're a female, sorry.  Pretend you're a guy).  Then one day, you come home from work to find your girl sitting alone in the bathroom.  Her pallid face frames a gaze that is fixed gravely on a plastic, urine soaked stick with two pink lines on it.

Once you recover from the shock, you realize that you've got 9 months to do some serious planning.

So you take a look at your finances and go over your options.  If you've got the cash, you could build a third room for junior. If not, then he'll just have to cramp your style for a few years and sleep in your room.  If you find yourself in a panic about how you're going to afford this kid, maybe you move all your crap and rent out the second bedroom.  If you're really well off, you might build junior a whole new floor, with a race car bed, a basketball court, and a zip line to the breakfast table.

Growing bigger muscle is a lot like convincing your body that it can afford to spend the money on that basketball court and zipline.  When you get in the gym and train, you're telling your body that there's a novel stressor in your life, and it needs to find a way to handle it.  The time you spend in the gym does NOT dictate how your body chooses to adapt to the issue.  

Here's the keystone: muscle growth above baseline is expensive and noncritical to survival.  You must understand that bigger muscles are a luxury that will ONLY be built if the body is fully capable of safely and comfortably spending the resources needed.  This article will focus on providing practical information on how you can signal your body to go ahead and start construction.


Factors That Govern Growth

1) Stress
In the context of training, this stress comes from our resistance exercise.  Physical stress sets the stage for muscle growth by placing a new demand on the body, and thus a subsequent need for adaptation.  It's extremely important to understand that stress equals potential.  Even highly experienced lifters sometimes forget that what they do in the gym merely creates the potential for growth; whether or not it happens depends on many other factors.  The question for this section then becomes, what stress maximizes growth potential?

It turns out that as far as muscle growth is concerned, it doesn't matter.

Intensity
You read right.  Multiple recent studies confirm that the type and intensity of exercise makes no difference whatsoever in terms of hypertrophy.  All that matters is whether or not you've recruited the entirety of muscle fibers, and that sufficient volume is reached.  This information equates to an astounding shift in common training methodology.

A study by Phillips et al, 2012, placed 18 20-22 year old men in 3 training groups and had them perform unilateral lower leg strength training programs for 10 weeks, 3 times a week.  What is remarkably interesting is that they had each subject perform 2 of the 3 programs on each separate leg.  Each subject performed a session of 3 sets to fatigue at 30% of 1RM (one repetition maximum), 3 sets to fatigue at 80% of 1RM and 1 set to failure at 80% of 1RM.

The results?  The 3@30% 1RM group and the 3@80% of 1RM group experienced nearly identical hypertrophy, with the 30% group gaining slightly more.  The 1@80% of 1RM group experienced some hypertrophy, but far less than the other two groups.  Keep in mind that responder/nonresponder issues were largely eliminated because these results were compared leg to leg across the same individual - same person, two programs, two different outcomes.

The take home point is that once you've selected a weight that CAN take you to failure (usually >25-30% of 1RM), and performed enough reps that you're fatigued enough to not be able to do another, you've automatically hit maximal recruitment.

How can that be?  How can a set at 30% of 1RM possibly recruit as many fibers as one at 80% of 1 RM, given that the body is adept as recruiting more or less exactly as many fibers as needed to perform a lift (this is why you don't smash yourself in the face when picking up a gallon of milk, etc.).  The answer is that during exercise, the smallest slow twitch fibers will be recruited first, but as they fatigue to the point where they cannot contract, recruitment will then progress to larger fast twitch fibers.  This continues until every fiber has been exhausted and work can no longer continue.  With a higher % of 1RM, more fibers are recruited earlier on and the newer ones are recruited more rapidly; with a lower %, less are utilized at first and newer fibers are recruited more slowly.  This is known as Henneman's size principle.  The end result is the exact same, regardless of how hard you think you've worked.

Note that there is an intensity cutoff.  A study by Holm, et al. had a similar set up, with 12 sedentary men performing unilateral quadriceps exercises 3x/wk, with one lifting at 15.5% of 1RM for 36x3 and one lifting at 70% of 1RM for 8x3.  The average growth for the 70% of 1RM group was  ~15%, while the 15.5% of 1RM group's growth was only ~5%.  I have issues with how this study handled nutrition, but the point is that there's a point where too little intensity and too many reps is sub-optimal for growth.  That line appears to be around the ~30% of 1RM mark.  I imagine that this threshold represents the line that separates training a muscle for strength/ hypertrophy and oxidative capacity and mitochondrial size.  

It turns out that any notions of perceived effort or high intensity are completely meaningless as far as size is concerned.  Pick a muscle(s) you want to get bigger, pick an exercise that hits that muscle, do literally any rep scheme you want until fatigue is reached, take a rest, and do it two more times.  You've just hit your maximum potential for muscle growth within that muscle.

Note: before anyone asks, yes, progressive overload is still crucial.  Your body still needs to be continually challenged for growth to occur.  What this means is that either reps need to increase or weight needs to increase regularly.  If using the high end of the rep scale, eventually weight will become too light (<30% 1RM) and will need to be increased.

Volume
Volume is a strange animal. We all know that volume is necessary to produce hypertrophy, and the results of hundreds of studies corroborate that fact that more volume leads to more growth, to a point. The problem is, there's a huge lack of science on the subject of exactly how much load is ideal.

We know that 3 sets produces more growth than 1 set. We also know that at a certain point, no further growth can be potentiated and in fact is detrimental. Where does that point lie? When do we stop gaining benefits out of additional sets? No one knows for sure, and it likely varies significantly from person to person. The author's opinion is that for most people, it's probably best to stick to 3 work sets per exercise.


Frequency
Proper training frequency is directly related to recovery ability.  Recovery ability is influenced by a lot of factors, which makes giving generic guidelines quite difficult.  In fact, recovery ability varies day to day and week to week depending on not only the mechanical stress, but also the emotional stress, levels of sleep, and nutrition profile.

In reality, this is where top level trainers earn their bread; keeping tight control of their athlete's volume and frequency and making sure they're always ready to hit their super compensation window (a topic for another day).  

For most, waiting ~48 hours between training the same muscle group seems to be the sweet spot.  Understand that your recovery is specific to YOU; just because your buddy can get away with training 6x/wk, it doesn't mean doing the same won't put you on a one way train to snap city.  

If you legitimately feel like crap or are too tired to get up and go, you're probably better suited to just take a rest day ("legitimately" being the operative term).  When in doubt, you really can't go wrong with 3x/wk.  

2) Inflammation
We've probably all heard that resistance training, especially the eccentric portion, causes micro-trauma.  This trauma has to be healed like any other wound, which is where the inflammation process comes in.

Immediately after a training bout, the process begins by flooding the damaged muscle tissue with macrophages.  Without getting too in depth, macrophages sweep in, eat up all the cells that are dead or damaged beyond repair through apoptosis, then secrete cytokines.  These cytokines mark the muscle tissue for repair, stimulate satellite cell response (more on this next section), and downregulate myostatin (a powerful inhibitor of muscle growth).

In practical terms, a depressed immune system means two things: A poor ability to initiate inflammation, and delayed inflammation response.  An inhibited or weakened immune system degrades the body's ability to perform an appropriate post exercise immune response significantly.  By the same token, chronic inflammation tends to have the same effect as induced immune depression, simply because resources are constantly being used to combat the source of perpetual inflammation.  The take home point is that sub optimal  immune function yields poor healing, which significantly impacts your ability to grow new muscle.

The obvious question is, how do we maintain an optimal immune system?  I'm going to assume that if you're reading this, you probably already engage in resistance training, eat a paleo-ish diet with the inclusion of fruits and vegetables which afford at least a marginal amount of anti-oxidants and micro nutrients, and that you already have a relatively healthy body weight.  The most common mistakes serious trainees make are A) not getting enough sleep, and B) training too frequently and interrupting the inflammation/healing process before it has a chance to finish.

Inadequate sleep has a number of very serious side effects which are detrimental to overall health and specifically to muscle growth.  If you're the type that thinks they can "get away" with 6 hours of sleep a night, then you can expect a depressed immune system, compromised ability to heal, down regulation of highly beneficial growth hormones, and heavily diminished muscle growth.

While we're on the subject, Brad Pilon has been doing a lot of research on the effects of chronic inflammation and muscle growth.  If it interests you, check out more on inflammation and muscle growth.

An issue you'll sometimes hear about is whether it's okay to take NSAIDs such as ibuprofen or naproxen sodium for muscle soreness.  Many argue that if acute inflammation response is critical to growth, then anything which inhibits that response must also inhibit growth.  There's a study by Mikkelson et al, 2009 which indicated that NSAIDs did inhibit growth pathways, but they used the NSAID idomethacin and administered it locally with a catheter.  Not exactly the same thing as popping two ibuprofen.  If you are so brutally sore from DOMS that you NEED something for the pain, then I wouldn't worry about it too much.

3a) Satellite Cell Activation
Human skeletal muscle is fairly unique in that it has the capacity for multiple nuclei.  Satellite cells are oligopotent stem cells which typically lie dormant on the surface of muscle tissue; when activated, they develop, split, and donate a new nucleus to existing muscle tissue.  This nucleus donation is required for regeneration and growth of muscle tissue.


I have no idea who made this image originally, and my Photoshop skills aren't good enough to make something comparable.  If anyone knows where it's from, please inform me so I can ask their permission to use it. 

There's a slew of information out there regarding the relationship between hypertrophy and stem cell activation.  A study by Petrella et al, 2008, had 66 healthy, untrained adults aged 20-75 perform a 16 week, 3x/week lower body resistance program consisting of x8-12 knee extension, leg press, and squats.  At the conclusion of the program, they  measured the contribution of satellite cells to hypertrophy.  Here's what they had to say about it:
In this relatively large cohort of 66 human subjects, the three-cluster model provides compelling evidence to support the concept that extreme myofiber hypertrophy is facilitated by satellite cell proliferation 
These cells come into play throughout our life cycle, as skeletal muscle is more or less constantly being damaged through normal activity.  The question is, how do we maximize satellite cell response to encourage not only repair, but growth of new tissue?

First and foremost, satellite cells respond proportionally the level of stress, and by extension, the level of damage within the muscle fiber.

Chen et al, 2005, notes that satellite cells are also a downstream target of androgens including tesosterone, though the mechanisms behind this relationship aren't fully understood.  The study cites quite a number of experiments involving animals and humans in which increased levels of testosterone are positively associated with a greater number of satellite cell activations.  It also does the same for other growth factors, including IGF-1.  Though we may not know at this time exactly how it works, we can safely conclude that upregulating testosterone and other growth hormones will also improve satellite cell response, and consequently, muscle regeneration and growth.

There's a relatively new, though fairly robust, body of information supporting the theory that creatine supplementation upregulates satellite cell activation in combination with resistance training.  Studies by Olsen, et al. and a few others have shown evidence supporting this claim.  I won't get into the nitty-gritty because I figure 90% of you already supplement with creatine; just consider it an added bonus.  

3b) mTOR/AMPK
The balance mTOR/AMPK is a huge topic that will be discussed in depth in future articles that deal with the larger scope of overall body recomposition.  For now, I'm going to keep this simple for the sake of brevity, but stay tuned if this topic interests you (which it should, it's extremely important).

The protein mTOR (mammalian target of rapamyacin) and its signaling pathway, the Insulin/PI3K/Akt/mTOR, is a downstream regulator of protein synthesis.  Downstream of what, you ask?  Chiefly insulin, amino acid availability, cellular energy status, and oxygen levels. Consider mTOR as a storage and synthesis anabolic pathway. 

AMPK (5' adenosine monophosphate activated protein kinase) is an enzyme which counterbalances mTOR.  It has a great many functions in the body, but we'll focus on AMPK's role in fat mobilization and oxidation, and that it stops protein synthesis cold.  Counter to mTOR, AMPK acts as a catabolic, lipolytic (fat burning), synthesis inhibiting pathway.

Really, the take home on the relationship between mTOR and AMPK parallels the relationship between most anabolic and catabolic hormones/pathways.  In healthy, disease free populations, mTOR and AMPK work in cyclic, oscillating conjunction to balance tissue synthesis and tissue removal.  As one goes up to perform a specific job, the other gracefully gets out of the way.  In diabetic/obese individuals, mTOR is chronically "turned on", while AMPK is chronically inhibited; interchange leptin/ghrelin, insulin/cortisol, and you start to get the picture that no hormone/enzyme/pathway isinherently good or bad, rather they each have their time and place.


For muscle growth, you need to inhibit AMPK and maximize mTOR involvement, period.  Please do not take that as me telling you mTOR=good and AMPK=bad, because that it is not the case.  Simply understand that after you've created the conditions for muscle growth via a training session, mTOR needs to come into play and AMPK needs to get lost. 


Maximizing mTOR
As stated, the mTOR pathway is activated by cellular energy status, nutrient availability, and growth factor availability.  What this realistically means is that post workout, you'll want to get essential aminos, particularly adequate leucine, into your body.  So, protein after a workout - quite the revelation, eh?

Obvious stuff aside, protein input is one component of mTOR.  Unfortunately, ignoring the other components causes mTOR activation to suffer significantly.  The other important triggers are the input of growth factors.  You'll want to do the following to maximize mTOR:

  • Spike insulin - simple sugars and fast proteins post workout are great for this
  • IGF1/2 - synthesized by downstream uptake of growth hormone
    • Growth hormone
      • upregulated by fasting, grhelin, sleep, hard exercise
      • inhibited by stress hormones - chiefly chronic cortisol - sleep deprivation


Where green arrows indicate activation, and red lines indicate inhibition.  Also shown: as ATP levels fall, AMPK levels increase.
 
Starting to make sense?  It might be hard to swallow, but adequate deep sleep and management of chronic daily stressors has just as much involvement with muscle growth as your lifting program and protein supplements.

mTOR is a metabolically costly process.  Positive cellular energy status is crucial for activating mTOR.  Simply put, you need to eat in significant excess of your maintenance calories.  On top of that, mTOR/AMPK are closely tied to ATP levels; if ATP goes down, AMPK goes up, which is quite undesirable during the growth window.  We've probably all heard that nutrient availability is crucial to muscle growth.  Actually, it's mandatory.  A Study by Oshiro et al. 2004, strongly indicates that without adequate resources, mTOR remains dormant.  In other words, don't even bother going to the gym without getting a pre workout and post workout in.

I don't want to get too much into the topic of fasting, but one of the largest benefits to intermittent fasting (I feel dirty even mentioning this without referring you to Martin Berkhan's Intermittent Fasting for more information) is that it paradoxically appears to up-regulate growth hormone AND AMPK.  AMPK is no surprise considering the complete absence of calories (obviously a catabolic state), but the growth hormone is a bit of a head scratcher.  Purely in the author's opinion, this seemingly conflicting signaling is likely due to the fact that when a person adjusts to intermittent fasting schedule, ghrelin entrains (a hunger hormone) to peak prior to the feeding window and growth hormone is maximized in anticipation of a huge input of calories- prime conditions for storage and growth with desirable calorie partitioning.  

The real dilemma is that exercise is a tricky stimulus.  On the one hand, it increases growth hormone and causes the micro-trauma necessary for satellite cell activation - and that's great for muscle growth.  On the other hand, it's also catabolic in that it increases AMPK and inhibits mTOR.  As strange as it may sound, to maximize growth you MUST arrest the catabolic effects of training and switch your body into a state where mTOR is cranking and AMPK is out of the way.

Lastly, let's discuss cardio.  Cardio increases AMPK, no way around it - and that's fine so long as it isn't during your growth period.  Do it earlier in the day, on a rest day, or even right after your workout  if you have to.

Putting It All Together
 Maximizing muscle growth comes down to your ability to consistently meet the following needs:
  • Mechanical stress - sufficient repetitions to achieve failure, sufficient volume (generally 3 work sets), compounds to maximally upregulate growth hormones including GH and test.
    • Requires progressive overload through perpetual increase of load or reps.
  • Emotional stress - get rid of it as much as humanly possible.  Daily stressors chronically upregulate cortisol and downregulate hormones which positively impact both growth and calorie partitioning including GH, test. 
  • Sleep - requirements vary, but if you're waking up tired each day or burning the candle at both ends, kiss your gains goodbye.  Same problems as emotional stress, but specifically poor sleep->low GH->less IGF1/2->mTOR inhibition.
  • Immune health - not always controllable, but ties in with stress management, adequate sleep, comprehensive diet, and preventing chronic inflammation.
  • Aminos - you probably already knew this, but never skip pre and post workout nutrition.  No aminos->no mTOR->catabolic environment.
  • Insulin - don't buy into insulin and carb fear mongering; if you want muscle growth, you want a big insulin spike post workout, and that means simple carbs and fast protein.
  • Recovery - varies, but in general  don't screw with it by training the same muscle group more than once every ~48 hours; if inflammation is still happening, you're doing more harm than good.
  • Energy status - insufficient calories inhibits anabolism; you simply won't grow without enough food.  Carbs are required to signal adequate glucose/glycogen availability for mTOR activation.
  • Supplements - most aren't worth the time, but get your creatine and a multivitamin/mineral in.

Notes And Causes For Pointless Worry
Here's something no one wants to hear: for an untrained individual, the first month or two of strength training generally doesn't contribute very much to muscle growth.  From your body's standpoint, there's simply no need for it.  It's much easier and more cost efficient to respond to the new stress through neurological adaptation.  The only answer is to keep on training and have faith that hypertrophy will follow nervous system adaptations.  

Let's return to the study by Palakal involving the 66 healthy, untrained adults.  25% of them were non or delayed responders.  It's a tough pill to swallow - the idea that a person is simply not genetically geared towards hypertrophy.  Furthermore, they reported the following:

No differences were found among the clusters in average training intensity, training volume, or program adherence; and the IIx-to-IIa myofiber type shift typical of resistance training was induced equally among all three clusters (4). Despite these similarities, the propensity for myofiber hypertrophy was vastly different.
It sucks, but response to a training program is nowhere near as predictable as many would have you believe.  We can design programs that are intended to give you the most growth potential, but there are so many genetic wildcards at play that it's simply impossible to truly know.  Why are some people non/less/delayed responders?  Maybe they have higher baselines levels of myostatin; maybe it's a relatively low satellite cell count, an unusual distribution of fiber types that don't hypertrophy all that well, a chronically elevated cortisol level, or any other number of mind boggling variables that exist within the body.  The harsh reality is that we control what's in our power to understand and manipulate, and the rest is up to the black box that is the inner workings of your unique human body.

While we're on the subject of sub optimal response to training, let's talk about age.  To make a long story short, growing muscle becomes harder as we age.  This happens for a great many reasons; down regulation of growth hormones, impaired healing response, and so on.  One factor that often goes unconsidered is degradation of the mechanisms which mediate satellite cell response.  The study by Chen et al, 2005 notes the following:
Striking differences can be observed in skeletal muscle between the adult and the aged in terms of muscle size and strength. One mechanism could be the decrease in the number of satellite cells with aging (Nnodim 2000). Another explanation is that the loss of muscle mass that occurs with aging is likely to reflect changes to the in vivo microenvironment required for the efficient activation and differentiation of satellite cells 
Another topic you'll hear discussed every now and again is that of myofascial bounding.  The first time I ever heard of this was reading over Dante Trudel's Doggcrapp training protocol, but there's a number of trainers who think it's crucial for hypertrophy.  The basic premise is that the tough membrane which surrounds muscle tissue,  your myofascia, needs to be stretched to keep it from constricting muscle growth.  Some even say that it can lead to hyperplasia (the growth of entirely new muscle cells, a very rare thing indeed).  They often cite a study done by Davis and Gonyea, 1989, which showed mild hyperplasia following significant hypertrophy in bird wings when they were stretched very far for lengthy periods.  Subsequent studies have neither confirmed nor dis-confirmed this effect, whether avian or human.  I honestly have no idea if there's any truth behind this extreme stretching business, but I'm mentioning it here if any adventurous spirit wants to give it a shot.



Note:  I welcome any and all feedback, both positive and negative.  Please feel free to comment with any suggestions below.

References
Oshiro N., Yoshino, K., Hidayat, S., Tokunaga, C., Hara, K., Eguchi, S., Avruch, J., and Yonezawa, K. 2004. Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function. Genes Cells 9: 359-366.

Shadrach, Jennifer L. ; Wagers, Amy J. Stem cells for skeletal muscle repair. PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Volume: 366 Issue: 1575 Pages: 2297-2306 DOI: 10.1098/rstb.2011.0027 Published: AUG 12 2011


L. Holm, S. Reitelseder, T. G. Pedersen, S. Doessing, S. G. Petersen, A. Flyvbjerg, J. L. Andersen, P. Aagaard, and M. Kjaer.  Changes in muscle size and MHC composition in response to resistance exercise with heavy and light loading intensity.  doi: 10.​1152/​japplphysiol.​90538.​ 2008.

Chen, Y ; Zajac, JD ; MacLean, HE. Androgen regulation of satellite cell function. JOURNAL OF ENDOCRINOLOGY Volume: 186 Issue: 1 Pages: 21-31 DOI: 10.1677/joe.1.05976 Published: JUL 2005


Steen Olsen, Per Aagaard, Fawzi Kadi, Goran Tufekovic, Julien Verney, Jens L. Olesen, Charlotte Suetta and Michael Kjær1.  Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training.  2006, doi:10.1113/jphysiol.2006.107359.  June 1, 2006 The Journal of Physiology, 573, 525-534.

Petrella J., Kim J., Mayhew D., Cross J., Bamman M. Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition: a cluster analysis. Epub 2007 April 18.

Mikkelsen UR, Langberg H, Helmark IC, Skovgaard D, Andersen LL, Kjaer M, Mackey AL. Local NSAID infusion inhibits satellite cell proliferation in human skeletal muscle after eccentric exercise. J Appl Physiol. 2009 Nov;107(5):1600-11. Epub 2009 Aug 27.

Alway, S. E., P. K. Winchester, M. E. Davis, and W. J. Gonyea. Regionalized adaptations and muscle fiber proliferation in stretch-induced enlargement. J. Appl. Physiol. 66(2): 771-781, 1989

Hay N., Sonenberg N. Upstream and downstream of mTOR. 10.1101/gad.1212704 Genes & Dev. 2004. 18: 1926-1945

Fielding, RA, Manfredi TJ, Ding W, Fiatarone MA, Evans WJ, and Cannon JG. Acute phase response in exercise. III. Neutrophil and IL-1 accumulation in skeletal muscle. Am J Physiol Regulatory Integrative Comp Physiol 265: R166-R172, 1993.

Shih, Michael. "keletal Muscle Hypertrophy Is Regulated via AKT/mTOR Pathway. BioCarta. Web. 21 Mar. 2011.

Cameron J. Mitchell, Tyler A. Churchward-Venne, Daniel W. D. West, Nicholas A. Burd, Leigh Breen, Steven K. Baker, and Stuart M. Phillips. 2012. Resistance exercise load does not determine training-mediated hypertrophic gains in young men