Muscle Mania Part V: Training Talk 01

Unraveling how volume, proximity to failure, and intensity impact hypertrophy

As previously promised, this marks the point in the Muscle Mania Series (I, II, III, IV) where we start to look at the effectiveness and efficacy of actual protocols for increasing hypertrophy. Here, we’ll start by introducing and assessing a few of the most commonly discussed resistance training variables: volume, proximity to failure, and intensity. Prior to diving in, we’ll cover some nuances to keep in mind when analyzing how training impacts hypertrophy and exercise outcomes overall. But, before any of that, check out the recap below to catch up on some key points we’ve covered thus far. 

Due to email length restrictions, I could not fit my reference list on this post, but you can find it here.

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Recap

• Muscles are ultimately composed of contractile proteins, called myofilaments, which are organized into structural units, called sarcomeres.

• Muscular hypertrophy, or muscular growth, involves building and incorporating myofilaments into sarcomeres to grow the overlying muscle.

• Muscle hypertrophy and atrophy are the results of an interplay between muscle protein synthesis (MPS) and muscle protein breakdown (MPB); interestingly, both processes are essential for building muscle. 

• Protein synthesis involves a macro-level signal (like lifting weights or eating protein) inducing a cellular signal at the micro-level, which provokes transcription of specific parts of the cell’s DNA (i.e. specific genes) into mRNA, the translation of that mRNA by ribosomes, and the construction of the correlating proteins. During muscle protein synthesis, those genes code for specific muscle proteins that will be incorporated into sarcomeres. 

• Our muscle cells utilize 3 pivotal processes to initiate and propagate hypertrophy: ramping up muscle protein gene expression by activating transcription factors, increasing nuclear capacity via satellite cell addition, and expanding translational capacity through ribosome biogenesis.

• Key molecules involved in hypertrophy-related cell-signaling include mTORC1, Akt/PI3K, Myostatin, MAPKs, and intracellular calcium; additionally, key hypertrophy transcription factors include MEF2, SMAD2/3, SRF, UBF, and Pax7. 

• Mechanical tension, the force placed on a muscle fiber during contraction, is likely the key mechanism for initiating hypertrophy-related cellular pathways; however, some suggest that metabolic stress and/or muscular damage play supportive roles in the process of instigating muscle growth.

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Salt Supply

As any competent 6th grade scientist learns during their lessons on the scientific method, it is important to recognize limitations in order to properly assess an experiment’s data. This is especially important when it comes to hypertrophy research, as the studies based around muscle building are particularly vulnerable to misinterpretation due to design issues. Firstly, these studies often consist of relatively small sample sizes (i.e. a small number of subjects) and often produce small effect sizes – the difference in results between the experimental group and the control group. Both of those variables, sample size and effect size, impact the power of the study, which is a measure of how likely the study is to find a significant result – in our case this would be that manipulating X variable impacts hypertrophy – if one exists. 

You can easily visualize this concept through the lens of flipping a coin, where the probability of landing either heads or tails is 50%. If you only flip the coin 5 times – representative of a small sample size – you can easily land on tails every time due to chance and walk away with the inaccurate perception that flipping a coin results in landing on tails 100% of the time. On the other hand, if you flip the coin 100 or even 1,000 times, you are much more likely to observe a result closer to the actual 50% probability of landing on either side of the coin. Now, imagine that, instead of a binary result of heads or tails, we are looking for what we expect to be a 5-10% relative difference in outcomes between a control and experimental group – an example of a small effect size – and we observe 10 subjects in each group – typical of many hypertrophy studies. Similar to the coin example, you can imagine that we could easily miss the mark of obtaining a proper result due to chance, as the margin of error is small due to the small difference in outcomes we are looking for – and, this doesn’t even take into account whether or not our study is long enough for the proper results to develop. 

Secondly, hypertrophy research suffers from the variability between individual responses to treatments due to biological variability. In other words, different people respond differently to different exercise interventions as a result of variations in genetics, stress levels, sleep quality, quantity, diet, etc. For this reason, virtually all hypertrophy studies produce a broad spectrum of subject responses across each group, in that, though Group 1 may show a significantly higher amount of hypertrophy than Group 2, the best responder from Group 2 could show greater hypertrophy than the worst responders from Group 1. Check out Figure 1 below, where each dot represents a percentage change in muscle size for a mock individual subject. 

Figure 1: Visual representation of how individual subject results vary in most hypertrophy research data. Note that, though there appears to be a trend of increasing hypertrophy moving from left to right based on where the dots cluster, some subjects in Group 1 and Group 2 outperform some subjects from Group 3. 

As you can see, though the mean results from a study may suggest that a certain intervention – in our case this might be what weight to use or how many sets to complete per muscle – is superior for producing hypertrophy, individual responses can still vary from that mean. In other words, an individual may find disagreement between how a given protocol works for them and how the protocol is, “supposed,” to work, according to the research. 

For all of these reasons – small sample sizes, small effect sizes, and large biological variability – experts in the realm of exercise science often place large value in solid meta-analyses that combine results from multiple studies as compared to viewing results from any single study as definitive. In addition, they recognize that the research, as a whole, only provides probabilities that X, Y, or Z will be most effective, and that those probabilities change on a case-by-case basis. Likewise, as we move on, I recommend taking the data covered below with a grain of salt and – rather than blindly following the research – combining expert opinions and study results with your own experience when considering your own exercise strategies.

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Progressive overload

Prior to understanding any of the training variables below, we should start with the backbone of all exercise programming: progressive overload. This concept serves as a methodology for continuously stimulating physical adaptation, whether it be sprinting speed, back squat strength, or bicep size, and it can be easily understood through the analogy of getting your cousin Sal’s attention at a crowded dinner table. At first, almost any communication – calling his name, poking him on the shoulder, or even just making eye contact – will suffice; however, after repeatedly using these same methods, Sal eventually goes numb to your signal, he stops responding. For this reason, you have to escalate your approach. On one hand, you could alter the intensity of your signal, perhaps by raising your voice, or even lowering it and repeatedly whispering his name like you’re delivering a prophecy in some creepy sci-fi movie. Either of these approaches may be enough to catch him off guard and elicit a response; however, he will ultimately become desensitized to them as well, requiring further innovation on your part. Maybe this time, you transform the approach entirely by making a hand gesture or tapping a fork to your glass. Due to their novelty, these signals are far more likely to gather Sal’s attention than the same old tactics you’ve been using during the past few year’s of family gatherings; furthermore, and interestingly, by switching to these non-verbal approaches, you will likely re-sensitize Sal to the classic forms of communication that had once lost their effect. 

This process of repeatedly renewing and renovating your method of eliciting a response from Sal models the principle of progressive overload, which – as the name implies – consists of continually switching up the stimuli in your training in order to challenge your body and produce further adaptations – in other words, to avoid plateaus. With specific regard to resistance training, this looks like altering the quantities, qualities, and types of reps, sets, and exercises you utilize. If you have ever followed a set protocol at the gym, track, or monkey bars for a prolonged period and found that your physical abilities eventually ceased to improve or even began to degrade, then you are familiar with the need for a progressive overload design. Put simply, the same way that Sal will start to ignore and block out your calls after you have gestured towards him the same way 100 times, your body will also dim down its adaptive responses to exercise if you do not provide some type of novelty in your training stimuli – i.e. heavier weight, more sets and reps, new exercises. And, this is the core of any physical training program: gradually modifying training variables to continually challenge your body and progress towards a desired training outcome. With that in mind – understanding that each concept below builds off of progressive overload – let’s dive into the actual variables we can manipulate to build more muscle.

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Volume 

If you took a stroll through Part IV of this series, then you are tracking that mechanical tension – the force induced on a muscle during exercise – appears to be the key mechanism driving hypertrophy; consequently, you understand that, if our goal is muscle growth, our focus is on total load and the duration of time our muscles are under that load (time under tension). In this regard, volume load, the total amount of weight moved during a training session – easily calculated as (weight) x (reps) x (sets) – is likely the cardinal variable in a resistance training program. (I)

Research around volume load generally comes in a couple of different flavors: volume per muscle group per week (i.e how many sets of bicep exercises completed each week) and volume per muscle group per training session (i.e how many sets of bicep exercises completed in each training session). In terms of sets per week, volume and hypertrophy seem to exist in a graded-dose response relationship, meaning that greater volumes produce greater hypertrophy up until a maximum threshold of beneficial volume. (I, II, III, IV, VI, VII) Where that maximum threshold – the point at which adding more weekly volume ceases to produce more hypertrophy – lies is still up for debate; however, some studies show hypertrophic benefits increasing with up to as many as 30-45 sets per muscle group per week. (I, II, VI, VII) 

In terms of volume per session, it appears that more sets produce more hypertrophy up until about 6-10 sets per muscle group per session where the benefits begin to plateau. (I, II, IV, VI, VII, VIII, XII) The data supporting this notion are multiple and diverse, consisting of research showing that activation of hypertrophy-related cell signaling molecules (p70SK6), number of satellite cells, and activation of ribosome biogenesis all increase with increasing sets per session without a clear point of regression.(VI, VIII, IX) As we discussed in Part III of this series, these markers are all suggestive of hypertrophy; additionally, data shows MPS and actual hypertrophy outcomes increase up to and level off at this 6-10 sets per session range. (I, IV, VI, VII) Notably, this supposed optimal 6-10 sets per muscle group per session range only applies when using rest intervals of 90-120 seconds or greater between sets – we will cover how rest intervals impact hypertrophy later on in the Muscle Mania Series. (VI, VII)

Another line of evidence supporting volume load as the pivotal variable for hypertrophy builds on the observation that manipulating other variables – such as intensity, frequency, and proximity to failure – while equating volume load does not lead to significant differences in hypertrophy.(I, III, X) In other words, as long as they achieve similar total volume loads – along with a few other prerequisites for hypertrophy, such as an intensity of at least 30% 1-rep-max and training to or near failure – subjects lifting at varying intensities, frequencies, or proximities to failure will ultimately elicit similar degrees of hypertrophy. Manipulating these variables without controlling for volume load, on the other hand, tends to lead to greater hypertrophy for the subjects acquiring greater volume load.(I, XI, XIV)

Though higher weekly volume and the 6-10 sets per muscle group per session range are believed to maximize hypertrophy, data shows that much lower volumes — as low as 3 sets per muscle group per week and 1-2 sets per muscle group per session — can produce meaningful hypertrophy as well, especially in untrained subjects (i.e. people who have not previously lifted weights regularly). (III, IV, XI, XII) With this in mind, one logical approach is for an individual to pursue their minimum effective dose when it comes to volume load, meaning that they would aim to use as little volume as needed to reach their desired amount of hypertrophy – which would look quite different for a professional bodybuilder than it would for a recreational lifter. Regardless of how much muscle they are looking to gain, by using the lowest necessary volume, they could leave room to add volume in the future to create the previously mentioned progressive overload. On the other hand, if they smash volume through the roof from the beginning, they leave themselves with less options when they reach an inevitable slowing in their results. Not to mention, this strategy allows them to achieve solid results in a more time efficient manner – they don’t need to spend 2 hours in the gym every time they lift if they’re just looking for a good chunk of the hypertrophic benefits. 

For a digestible and comprehensive exploration of all things volume, check out James Krieger’s Set Volume For Muscle Size: The Ultimate Evidence Based Bible.

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Effort/Exertion (Proximity to Failure)

In my opinion, the degree of effort you put towards your sets, commonly encapsulated by the term proximity to failure, sits right behind volume in terms of importance for inducing hypertrophy. As its name implies, proximity to failure describes how closely you approach the point where you can no longer lift the weight with proper technique (i.e. without swinging, yanking with your back, or incorporating muscles other than those you are targeting with the given exercise), also known as volitional failure. This term can become hazy, in that it is unlikely that you will reach true failure – easily visualized as the amount of reps you could do with your life on the line – while repping it out at the cable machine of LA Fitness; additionally, the situation gets foggier when considering a hierarchy of failures, some surpassing the previously described, “good technique,” metric of failure by using a partner to facilitate reps, safely cheating the concentric portion of the exercise to continue reaping benefits from the eccentric portion, and/or completing half-reps. With that said, most of the research on training to failure uses the traditional volitional failure definition; however, even with this uniform definition, the data remains somewhat mixed. 

In general, it appears that training to absolute failure does not provide superior hypertrophy to training near failure, provided that volume is equated (I, X, XIV); nonetheless, it is reasonable to imagine that there is a minimum threshold of proximity to failure for inducing hypertrophy, as completing something like 10% of the total reps one could possibly complete is unlikely to be sufficient. Similar to that for weekly volume load, the exact location of that threshold is still to be determined. (I,X)

Though training near failure – which amounts to 6-2 reps shy of failure in some studies (XI, XIV) – seems to be enough on a general basis, this appears accurate only when total volume load is equated between groups; furthermore, some studies suggest that training to failure does provide better hypertrophy outcomes for trained individuals (i.e. people who have been resistance training regularly for ~2-5 years). (I, X, XI, XIII) In theory, this makes sense, as individuals with greater training experience could become desensitized to the stimulus of resistance training, in which case proximity to failure could be used to achieve progressive overload. Also, some data implies that training to failure is important when using lighter weights (<60% 1RM), which is supported conceptually when considering that maximal motor unit recruitment (i.e. the maximum amount of nerves and their corresponding muscle fibers activated) occurs at 60%-85% 1RM. (I, X, XVII) In other words, training to a further degree of muscular fatigue may be required with lighter weights to assure the recruitment of motor units and muscle fibers that would otherwise not be used to lift those lighter weights. (I, X)

All of this taken into account, training to failure does not appear to negatively impact hypertrophy and could be used to reach higher volume loads with less total sets; contrarily, training to absolute failure on every set could ultimately reduce volume load if it decreases the amount of reps one can complete or the amount of weight they can lift in the follow-on sets of a training session. (I, X) For this reason, it may be most beneficial to train near failure (~5-1 reps short of failure) on most sets while sprinkling in sets to failure in the later sets of a training session; furthermore, as Dr. Brad Schoenfeld recommends in his textbook, Science and Development of Muscle Hypertrophy (I), one can also cycle the proximity to failure in their training sessions – periodically utilizing more or less sets to failure – offering another tool for implementing progressive overload. 

Check out Grgic Et. al.’s review here for a deeper dive on training to failure.

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Intensity 

Although volume appears to be the central variable of concern for hypertrophy, you cannot have a conversation about volume without discussing intensity, or the amount of load you are lifting relative to your strength. Not only is this variable functionally important, as it is critical to reach a minimum threshold of intensity to stimulate optimal and even any hypertrophy – likely the reason that endurance exercise, such as running or cycling, does not lead to significant hypertrophy despite creating large amounts of metabolic stress – it is important because nobody cares about your per-session volume load – they want to know how much you can squat and bench. 

Intensity is generally based off of an individual’s 1-rep-max (1RM), or the maximum amount of weight they can lift a single time for a given exercise. Interestingly, and despite the controversy over whether lifting relatively heavier or lighter weights will lead to the most gains, research shows that you can achieve significant and comparable amounts of hypertrophy with weights ranging from 30%-90% of 1RM, provided the sets are taken to failure and volume load is equated. (I, V, XV, XVI)  Fortunately, this makes intensity an easy target for manipulation, allowing you to avoid plateaus by cycling different stimuli – smaller sets with heavier weights, larger sets with lighter weights, and everything in between – across a multi-month training program. 

In addition, different intensities theoretically offer different routes to increasing volume load in the long run, as higher rep ranges with lower intensities tend to improve your ability to buffer metabolic stress, and lower rep ranges with higher intensities tend to improve your strength. Both of these benefits can theoretically increase the amount of weight you can use for intermediate rep ranges (~8-12 reps per set) and increase your volume load as a consequence.  I find that rotating through a variety of rep ranges is beneficial from a psychological perspective as well, in that switching to some heavier, compound lifts can be refreshing after a month or two of knocking out lateral raises and tricep extensions for sets of 20-30 reps to failure.  

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Stay tuned for Part VI of the Muscle Mania Series where we’ll break down some more training variables and how they can contribute to building muscle. For now take a look at the link below for more Shortcuts similar to this one.

Best of Shortcut U: First Year Edition