Sports science and strength and conditioning experts have been speculating about the mechanisms that create skeletal muscle hypertrophy for decades. One of the first mainstream fitness writers to summarize the popular scientific mechanisms of the time was Lyle McDonald. In his 1998 book on ketogenic dieting, Lyle proposed 4 distinct mechanisms of hypertrophy: tension, metabolic work, eccentric muscle actions, and hormonal response to weight training. This was 18 years ago and was the best synopsis of the research at the time.
Brad’s Conceptual Hypertrophy Model
Twelve years later, in 2010, Brad Schoenfeld published a review article in the Journal of Strength & Conditioning Research titled, The Mechanisms of Muscle Hypertrophy and Their Application to Resistance Training. In this classic article, Brad proposed that hypertrophic stimuli from resistance training fall into three categories: mechanical tension, metabolic stress, and muscle damage. Brad didn’t invent these categories out of thin air. Although he was the first link cell swelling research to da pump in bodybuilding and comprehensively summarize and categorize the literature pertaining to skeletal muscle hypertrophy, the three mechanisms had been proposed long before Brad popularized them. Rather, he conducted a thorough examination of the literature and provided a research-based case as to why they may be involved in the hypertrophic response to resistance training.
We’ve learned a lot about muscle hypertrophy in the past couple of decades since Lyle first proposed his four mechanisms. For example, the hormone hypothesis has largely been debunked, thanks in large part to research professor Stu Phillips. Even since Brad’s classic paper was published 6 years ago, we’ve learned a good deal about muscle hypertrophy. Much of this knowledge is derived from curious, passionate researchers like Stu and Brad, as they are constantly conducting and publishing new studies to expand upon what we presently know.
In recent months, we’ve seen a lot of activity online from various experts weighing in on their beliefs pertaining to muscle hypertrophy. From numerous articles I’ve read and discussions I’ve had with different individuals, it’s quite intriguing to note the different opinions and interpretations of the research. Could it be that just as in the case of the hormone hypothesis, some of the presently proposed mechanisms of hypertrophy don’t pan out? Could Brad be wrong in his overall views on the drivers of muscle hypertrophy?
Alternative Conceptual Hypertrophy Model
Some researchers have put forth the hypothesis that motor unit recruitment/activation almost solely drives the hypertrophic response. This is in stark contrast to Brad’s three-component model. These individuals do not believe that metabolic stress, cell-swelling, or muscle damage are big drivers of hypertrophy, pointing out that the research pertaining to hypertrophy and metabolic fatigue and cell-swelling is scant.
They postulate that as long as one performs sets to momentary muscular failure, then full motor unit recruitment in the muscle will be achieved (assuming it’s a good exercise for that muscle). Now, research shows that heavy loads lead to greater peak EMG amplitudes than lighter loads, so shouldn’t this infer greater hypertrophic potential? Not so fast…
Recent interpretations of EMG data have been criticized (spearheaded by Andrew Vigotsky) because researchers link amplitude with motor unit recruitment. The EMG signal is mainly influenced by motor unit recruitment and rate coding (firing rates), but as fatigue sets in, the EMG signal becomes more complicated. During a high-rep set with lighter loads, the EMG signal changes under fatigue as firing rates diminish and peripheral factors (mainly intracellular action potentials which are mediated by calcium levels) enter the mix. Therefore, we can’t use EMG to fully predict hypertrophic responses or motor unit recruitment. More complicated EMG techniques and analyses are needed to distinguish actual motor unit recruitment, and longitudinal training studies are needed to show hypertrophy.
However, it is clear that EMG research on heavy versus light loads using the same exercise are likely misleading, as one could receive lower peak EMG activity but still receive the same hypertrophy stimulus if the motor units are recruited for sufficient time throughout the set. If the set was carried out to failure, it is feasible that all the motor units would eventually be activated according to Henneman’s size principle, and each of the individual fibers that comprise the different motor units would be activated according to the all-or-none law, thereby creating the requisite hypertrophic stimulus for all of the muscle’s fibers. Whether this plays out in practice has yet to be determined. But even if so, this doesn’t invalidate EMG research; EMG is a highly valuable tool in the sports scientist’s arsenal. It just means you have to know what the EMG signal does and does not tell you.
More Thoughts on Hypertrophy
Now, there’s still plenty more to the hypertrophy story. Some exercises better target certain regions of muscles. And since muscles can have unique EMG activation angle curves, some exercises will necessarily lead to greater activation than others if their torque angle curves match up closely with the EMG activation curves and peak torque is achieved at the same joint angle as peak EMG amplitude. Finally, some lighter compound exercises may not fully exhaust all the prime movers, and therefore Henneman’s size principle wouldn’t apply and all the motor units wouldn’t necessarily be recruited. In other words, we can’t assume that any exercise that works a muscle will achieve full motor unit recruitment as long as failure is reached.
Personally, I use the shotgun approach in my training, my training of clients, and my online programs, simply because we don’t currently have all the answers. I make sure to hit the muscles from multiple angles and vectors with varying rep ranges in order to ensure development of each subdivision and ensure that the tension stimulus, metabolic stress stimulus, and damage stimulus are delivered in appropriate amounts. But in time, we may figure out that we don’t need a shotgun; all we might need is a pistol.
I currently believe that tension is the primary driver of muscular hypertrophy. I believe that metabolic stress, muscle damage, and cell-swelling are additive to the tension-induced hypertrophic response. I think that many of these factors could have a high genetic influence, with some folks responding way better to certain stimuli than others. Most clients end up receiving and gravitating toward similar program designs, but I can think of numerous clients over the years that seemed to respond better to high reps, or less sets, or certain exercises over others. This isn’t controlled research, I’ll admit; it’s a bunch of case studies. However, there is indeed research on genetics to back up some of my findings in the gym. Perhaps there are individuals who respond more favorably to tension, or metabolic stress, or muscle damage.
I realize that my current beliefs are highly influenced by my discussions with Brad. I don’t regularly read all of the hypertrophy research (especially the signaling research); I’m more focused on biomechanics research (which is why Brad and I get along so well – the two go hand-in-hand). In downloading all of the sports science articles each month for Chris and my research review, I make sure that I pull up every article I find pertaining to the physiology of muscle hypertrophy and then send them to Brad so that he has them. I trust that Brad will read them and update his knowledge base accordingly, which will transfer over to me during our frequent weekly phone conversations. Or in reading the free books Brad sends me to review; his latest masterpiece Science and Development of Muscle Hypertrophy is now on Amazon.
However, I’m highly open to changing my mind in time. Brad and I have been wrong in many of our hypotheses, and we’ve changed our tunes accordingly. I would personally love for the alternative hypertrophy model to be correct – it would make things so much simpler in the gym.
For building glutes, I’d no longer have to perform damaging exercises such as walking lunges or Bulgarian split squats that stress long muscle lengths, I’d no longer have to go super heavy and load 6 plates on each side for deadlifts and hip thrusts, and I’d no longer have to strive for a pump or a burn with frog pumps, band hip thrusts, or bodyweight back extensions.
I could just bust out multiple sets of hip thrusts in any rep range I desired and achieve maximal glute growth, since hip thrusts highly activate the upper and lower gluteal regions. But I just can’t seem to fully embrace this model.
And by the way, this doesn’t just apply to glutes – it applies to every muscle. No more RDLs and SLDLs to stretch the hammies under activation; leg curls alone will suffice. No more bottom-half push-ups and cable crossovers to pump up the pecs; normal sets of incline press will suffice. This is such a more eloquent model. I hope it’s that simple!
Interview with Dr. Brad Schoenfeld
I decided to reach out to Brad Schoenfeld to shed some light on these recent topics of discussion.
Bret: Are you open to being wrong about your three-component model of mechanisms of hypertrophy?
Brad: Certainly I’m open to being wrong. The only goal of a true scientist is to seek the truth. I’ve changed my views on many aspects of exercise and nutrition over the years in the face of emerging evidence, and should evidence come out that shows one or more of the mechanisms are not related to growth, I’ll be the first to embrace that research and reformulate my opinion.
Along these lines, it’s important to understand that the mechanisms I’ve laid out are a theoretical construct based on current research and their implications for growth in an applied setting. The problem is that there has been no direct research on the topic that would allow me to be confident in making definitive claims. Rather, I would say that there is a fairly strong hypothetical rationale for these mechanisms, but without direct research my theory remains speculative. What’s more, if the theory is indeed true up, we do not know whether there is a synergism between the mechanisms, or if they are redundant in some capacity or beyond a certain threshold.
Without question mechanical tension is a driving hypertrophic force, but is there an additive benefit to generating metabolic stress (which can be defined as the exercise-induced buildup of metabolites including lactate, hydrogen ions, and inorganic phosphate)? Can’t say, as no studies have looked at the topic. Certainly there is a good logical rationale supporting a role for metabolic stress in promoting a hypertrophic response.
For example, it has been well established that blood flow restriction (BFR) training is associated with high levels of metabolic stress. Simply restricting circulation with an inflatable cuff for five bouts of 5 minutes twice a day was shown to be sufficient to preserve leg muscle mass in subjects immobilized in a cast for 14 days (Kubota et al 2008). Moreover, there is evidence that walking under conditions of blood flow restriction produce significant increases in muscle growth in a cohort of young men (Abe et al 2006). And hypoxic training, which tends to increase metabolic stress, has been shown to enhance muscle growth even when training is carried out at similar levels of volitional effort (Kurobe et al 2014). Whether these effects are directly related to metabolic stress cannot be determined, but at the very least this research would seem to indicate that factors other than mechanical tension are involved in muscle remodeling.
Moreover, muscle damage will necessarily occur to some extent during training. It’s clear that there is a threshold beyond which it compromises growth. But is there a sweet spot for growth or is it simply permissive within a given range? There is evidence that training at longer muscle lengths enhances the hypertrophic response to lifting (Noorkõiv et al 2014) and evidence that muscle damage is greater with longer muscle length training (Baroni et al, 2016; Clarkson et al 2002). Is the correlation coincidence or is there a cause/effect? And it’s well-established that muscle damage increases satellite cell function (Schoenfeld, 2012); how much of an effect, if any, does this have on long-term muscle growth? These are questions that have yet to be answered, and given the difficulty in investigating the topic, it will be a while before we are able to get a better handle on the complexities.
What is quite clear from the literature is that both metabolic stress and muscle damage mediate factors believed to promote hypertrophy including satellite cell function, acute inflammatory processes, acute reactive oxygen/nitrogen species activity, cell swelling, intrinsic myokine production, and others. For further insights, those interested can read the research reviews I’ve written exploring the rationale and limitations of current evidence at the links below:
Bret: If so, what type of research would be needed to change your mind (no matter how complicated and unrealistic)?
Brad: As noted above, the issue when it comes down to understanding mechanistic factors in an applied science such as exercise is that it’s extremely difficult to tease out the variables so you can draw cause/effect conclusions. For example, we can compare very low repetition training with long rest intervals to minimize metabolic stress versus a moderate/high rep protocol with shorter rest and compare growth between conditions as I did in a previous study (Schoenfeld et al 2014). If we find that both groups saw approximately equal gains as was shown in my study, can we then conclude that mechanical tension and metabolic stress both have equal effects? Or are there perhaps other factors involved that confound results, such as total time under tension? Impossible to say.
Similarly, how do we completely separate the effects of mechanical tension from muscle damage? There is always going to be some degree of damage, so ultimately it comes down to trying to ascertain whether graded increases in damage promote a greater effect, and if so, what is the threshold beyond which the benefits on hypertrophy cease. We simply don’t have the means to properly study these nuances at present and it’s difficult for me to envision how these factors would be able to be isolated without seriously compromising generalizability to traditional resistance training practices.
Bret: What sayeth you in response to the theory that motor unit activation drives hypertrophy, and as long as volitional failure is reached for a particular load, all motor units in the muscle will be activated according to the size principle, and optimal hypertrophy will be achieved.
Brad: It is well established that MU activation drives hypertrophy – ultimately maximal hypertrophy involves full recruitment of the spectrum of MUs while maintaining high firing rates in these MUs for a sufficient period of time (which is the essence of MU activation). The question as to whether adaptations are the same between any loading intensity given training to muscular fatigue remains speculative, and there is reason to hypothesize this isn’t the case.
There is now compelling evidence that a muscle will hypertrophy using even very low loads. Our lab has shown this happens with trained subjects (Schoenfeld et al 2015), and recent research out of Stu Phillips lab confirms our findings (Morton et al, 2016). (Side note: This is one of the aforementioned topics that I’ve changed my opinion on based on emerging evidence – I’d previously held the belief that lower loads produced only minimal hypertrophic increases).
That said, many things remain to be determined here. EMG work compellingly shows higher amplitudes associated with high vs low load training to failure. The applicability of these findings to training-induced adaptions is not clear, but they at least provide a reason for caution when attempting to conclude that it all comes down to training to failure. Moreover, from a mechanistic standpoint we can’t necessarily assume that results between loading conditions are purely a mechanical phenomenon – effects mediated by metabolic stress and/or muscle damage may be involved in the response. No study has endeavored to look at mechanistic actions, and I can’t fathom how this could be accurately assessed.
Moreover, there is evidence that the hypertrophy manifests differentially at higher versus lower loads, with greater type I increases noted in lower load training and greater type II increases noted in higher load training (although the recent study from Stu’s lab seems to contradict these findings and show no differences). And it’s also possible that some of the hypertrophic increases in the lower load condition may be related to increases in other non-contractile tissue (i.e. mitochondrial content). Finally, the short-term nature of resistance training studies leaves open the possibility that results may be at least in part attributed to a novelty effect and that findings might diverge over time.
So my feeling based on current evidence and practical expertise, and given the possibility of differential effects between loading zones, is that training through a spectrum of repetition ranges is best for those looking to maximize muscle growth. Our recent study looking at a varied versus constant loading protocol suggests a potential benefit to such an approach, at least for increasing growth in the upper body musculature (Schoenfeld et al 2016). But science is ever-evolving and, as previously noted, I’ll be the first to change my opinion in the face of compelling new evidence
- Abe, T, Kearns, CF, and Sato, Y. Muscle size and strength are increased following walk training with restricted venous blood flow from the leg muscle, Kaatsu-walk training. J. Appl. Physiol. 100: 1460-1466, 2006.
- Baroni BM, Pompermayer MG, Cini A, Peruzzolo AS, Radaelli R, Brusco CM, Pinto RS. Full range of motion induces greater muscle damage than partial range of motion in elbow flexion exercise with free weights. J Strength Cond Res. 2016 Jul 7. [Epub ahead of print]
- Clarkson PM, Hubal MJ. Exercise-induced muscle damage in humans. Am J Phys Med Rehabil. 2002 Nov;81(11 Suppl):S52-69. Review.
- Kubota, A, Sakuraba, K, Sawaki, K, Sumide, T, and Tamura, Y. Prevention of disuse muscular weakness by restriction of blood flow. Med. Sci. Sports Exerc.40: 529-534, 2008.
- Kurobe K, Huang Z, Nishiwaki M, Yamamoto M, Kanehisa H, Ogita F. Effects of resistance training under hypoxic conditions on muscle hypertrophy and strength. Clin Physiol Funct Imaging. 2015 May;35(3):197-202.
- Morton RW, Oikawa SY, Wavell CG, Mazara N, McGlory C, Quadrilatero J, Baechler BL, Baker SK, Phillips SM. Neither load nor systemic hormones determine resistance training-mediated hypertrophy or strength gains in resistance-trained young men. J Appl Physiol (1985). 2016 May 12:jap.00154.2016. doi: 10.1152/japplphysiol.00154.2016. [Epub ahead of print]
- Noorkõiv M, Nosaka K, Blazevich AJ. Neuromuscular adaptations associated with knee joint angle-specific force change. Med Sci Sports Exerc. 2014 Aug;46(8):1525-37
- Schoenfeld BJ, Ratamess NA, Peterson MD, Contreras B, Sonmez GT, Alvar BA. Effects of different volume-equated resistance training loading strategies on muscular adaptations in well-trained men. J Strength Cond Res. 2014 Oct;28(10):2909-18
- Schoenfeld, B.J., Peterson, M.D., Ogborn, D., Contreras, B., Sonmez, G.T. (2015). Effects of low- versus high-load resistance training on muscle strength and hypertrophy in well-trained men. Journal of Strength and Conditioning Research, 29(10):2954-63
- Schoenfeld, B.J., Contreras, B., Ogborn, D., Galpin, A., Krieger, J., Sonmez, G.T. (2016). Effects of varied versus constant loading zones on muscular adaptations in well-trained men. International Journal of Sports Medicine,37(6):442-7