I'll admit it, before last month I'd never heard of Brad Schoenfeld.

It appears he's certainly been around the fitness block. He's published numerous books, appeared on numerous television shows, owns his own personal training facility, is an adjunct professor, and has earned multiple degrees and certifications.

Still, I didn't know he existed.

That was before I read his October 2010 article in the Journal of Strength and Conditioning Research entitled, The Mechanisms of Muscle Hypertrophy and Their Application to Resistance Training. This was quite simply the most comprehensive and succinct article on hypertrophy training I've ever read. If you're interested in hypertrophy and don't mind immersing yourself in some high-level science, then I suggest you find a way to access this article.

Anyhow, I was intrigued enough to contact Brad and ask him some questions about training for muscular growth. Forgive me if some of this stuff is a little too science-geeky, especially in the first part of the article, but that's what happened when two hypertrophy geeks get together.

T-Nation: Thanks for agreeing to do this interview, Brad. I'm curious as to how you found the time to compile all of the research that went into your article...was this just something you whipped up on a whim, or was it a work in progress over a period of many years?

Brad Schoenfeld: My pleasure, Bret.

The research review on the mechanisms of muscle hypertrophy was the culmination of many years of studying and analyzing thousands of research studies on the subject. I'm a self-professed research geek--I spend upwards of about 2 hours a day poring over research on exercise and nutrition, primarily as it relates to body composition.

Muscle hypertrophy, in particular, is a topic that is of primary interest to me. I've been a competitive natural bodybuilder myself, and have worked with many high-level physique athletes at the national and professional level.

Unfortunately, most physique athletes train very unscientifically. Their training is based on gym lore and mythology, leading to substandard results. It's therefore very rewarding for me to contribute to the body of literature on the topic and hopefully foster a greater attention to scientific training for hypertrophy.

T-Nation: Well you did a great job. Let's plow right in. What are the different ways a muscle grows, and what are the primary methods of causing muscles to grow?

Brad Schoenfeld: There are two basic types of hypertrophy, contractile hypertrophy and non-contractile hypertrophy (i.e. sarcoplasmic hypertrophy).

Contractile hypertrophy can manifest as either addition of sarcomeres in series or in parallel. In-series hypertrophy is not thought to significantly contribute to hypertrophy in typical training protocols (it's primarily seen after immobilization in a cast, or when persistently exercising at an incline on a treadmill), meaning that adding sarcomeres in parallel is the primary mechanism of contractile hypertrophy for those who lift weights.

Editor's note: In layman's terms, in-series hypertrophy refers to muscles growing by actually getting longer, like adding segments to a rope. For instance, if you were to hyperextend a limb and place a cast on it to hold it in that position, the stretched muscle would actually grow longer by adding additional sarcomeres. On the other hand, in-parallel growth means exactly that, sarcomeres being added next to each other like sardines being added to a tin.

Sarcoplasmic hypertrophy, on the other hand, is an increase in non-contractile elements within a muscle (collagen, glycogen, etc.). One of my mentors, the late Mel Siff, introduced me to the concept of sarcoplasmic hypertrophy years ago and there's a good deal of research supporting its presence.

While sarcoplasmic hypertrophy is often called "non-functional," this actually may not be the case. There's evidence that the increased hydration of the cell associated with sarcoplasmic hypertrophy may mediate a hypertrophic response, thus leading to subsequent increases in contractile hypertrophy.

Editor's note: Hydration can cause cell growth because, as the liquid exerts pressure against the cell wall, it's perceived as a threat to cellular integrity and the cell responds by reinforcing it's structure, i.e., growth. This is one of the mechanisms by which creatine is thought to work, as it increases a cell's fluid volume, which may then promote cell growth.

On the other hand, there's little research substantiating that hyperplasia (i.e. splitting of muscle fibers) contributes significantly to hypertrophy in humans.

Research shows three primary methods by which resistance training causes hypertrophy: mechanical tension, muscle damage, and metabolic stress. Each of these factors mediates various processes that ultimately act on myogenic pathways to either increase protein synthesis and/or decrease protein breakdown.

Moreover, there's evidence that these factors can have an additive effect on hypertrophy when combined in proper context.

T-Nation: When we look at bodybuilders versus powerlifters, how do the muscular adaptations differ between the two types of training?

Brad Schoenfeld: While both bodybuilders and powerlifters tend to display impressive muscularity, the bodybuilders traditionally show the greatest hypertrophy. Studies show that at least some of the increased hypertrophy in bodybuilders is due to an increase in non-contractile elements, presumably due to differences in training methodology.

However, as previously noted, the increased sarcoplasmic hypertrophy may ultimately lead to greater increases in contractile hypertrophy.

T-Nation: Please talk briefly about mechanical tension and metabolic stress. Should our goal be to maximize one or the other during a workout or to achieve a proper blend of the two stimuli?

Brad Schoenfeld: Simply stated, mechanical tension is the amount of tension developed by muscle fibers in response to a stimulus. This tension can be developed either by static or dynamic muscle activity (i.e., traditional resistance training), or by chronic stretch.

It is believed that mechanically induced tension disturbs the integrity of skeletal muscle, causing mechano-chemically transduced molecular and cellular responses in myofibers and satellite cells. Alternatively, metabolic stress results from the buildup of various metabolites (e.g., lactate, hydrogen ion, inorganic phosphate, creatine, etc.), and is generally maximized by anaerobic glycolysis as well as muscle ischemia.

Based on the body of available research as well as years of personal data working with physique athletes, I believe there is a threshold of mechanical tension that needs to be reached during training to elicit muscular gains. Beyond this threshold, metabolic stress becomes increasingly important to maximizing the hypertrophic response.

I should also point out that muscle damage is a part of the puzzle here. Specifically, damage to myofibers generates an acute inflammatory response that has been shown to mediate hypertrophic processes, including the release of various growth factors that regulate satellite cell proliferation and differentiation.

Given that muscle damage is brought about primarily by eccentric exercise, this reinforces the need to emphasize the eccentric portion of each lift.

T-Nation: What are the primary "anabolic" hormones in the body that we should be trying to maximize in our training?

Brad Schoenfeld: The two primary anabolic hormones are IGF-1 and Testosterone. I'm sure everyone knows about the anabolic properties of Testosterone. Interestingly, significant correlations have been found between training-induced elevations in Testosterone and muscle cross sectional area. This suggests that in addition to the importance of chronically elevated Testosterone levels, acute, exercise-induced elevations in Testosterone may also play an important role in muscle hypertrophy.

IGF-1 is a peptide hormone with structural similarities to insulin. One of the isoforms of IGF-1, called mechano growth factor (MGF), is preferentially upregulated in response to mechanical signaling and therefore appears to be particularly important to the growth process.

IGF-1 has been shown to induce hypertrophy in both an autocrine and paracrine manner, and exerts its effects directly by increasing the rate of protein synthesis in differentiated myofibers as well as through mediating the proliferation and differentiation of satellite cells.

Growth hormone (GH) also seems to play a role in hypertrophy, although its mechanisms are less clear than either IGF-1 or Testosterone. Research suggests that GH is primarily involved in the hypertrophic response in a secondary fashion, seemingly by mediating IGF-1 production.

Some people dismiss the hypertrophic role of GH based on studies using exogenous GH injections. However, these protocols do not replicate the large spikes in GH seen post-exercise, nor do they take into account the time course of GH elevation in conjunction with myotrauma.

Moreover, over 100 molecular isoforms of GH have been identified, yet the vast majority of this research has been carried out solely on one isoform, the 22 kDa isoform.

T-Nation: Many strength coaches hate on "pumping" training, saying that there is no evidence that trying to achieve a pump leads to increases in hypertrophy. Are these coaches correct?

Brad Schoenfeld: Before answering the question, it's important to look at the etiology of the muscle "pump." Basically, the pump is caused by a buildup of fluid within the cell, facilitated by the accumulation of metabolic byproducts, which function as osmolytes.

Editor's note: Osmolytes are organic compounds that maintain cell volume and fluid balance.

Studies show that intracellular hydration (i.e., cell swelling) can mediate hypertrophy both by increasing protein synthesis and decreasing proteolysis. Thus, there is a physiologic basis by which the pump may augment hypertrophy and it would be imprudent to dismiss this potential role.

T-Nation: Does this mean that we should solely seek "da pump" during our workouts or should we also be thinking about setting PR's and progressive overload?

Brad Schoenfeld: I certainly wouldn't say that we should "solely" seek a pump during training. Any training protocol, including those targeting hypertrophy, must have progressive overload to bring about adaptation. It's a central tenet of exercise and is by all accounts, immutable.

That said, the cell swelling effect of a muscle pump would seem to provide an additive effect to the hypertrophic response and this role should not be dismissed.

T-Nation: Is there such thing as "Irrational Hypertrophy," and if so, what is it?

Yet another editor's note: Irrational hypertrophy is the concept that muscle growth simply can't occur when the cell lacks sufficient resources. These resources could simply be lack of calories, lack of protein, or lack of some intermediate metabolic chemical.

Brad Schoenfeld: I've heard the term "irrational hypertrophy" mentioned in terms of cells lacking the energy systems required to support synthesis and maintenance of new muscle proteins, but this is generally not a limiting factor in hypertrophic training protocols.

There is evidence to support the concept of a myonuclear domain, which proposes that the myonucleus regulates mRNA production for a finite sarcoplasmic volume and that any increases in fiber size must be accompanied by a proportional increase in myonuclei (either in size or number of myonuclei).

Satellite cell activity is purported to be the primary mechanism regulating myonuclear domain, as satellite cells donate nuclei to the muscle fiber. Conceivably an inability to increase myonuclei could result in "irrational hypertrophy" and it's possible that training methodology could play a role in the process.

T-Nation: On a personal note, I've noticed that natural lifters seem to need to hit the muscle groups more frequently than one time per week for optimal hypertrophic results. Many bodybuilders hit their muscle groups one time per week and achieve great results, but they're taking exogenous anabolic steroids, human growth hormone, IGF-1, and insulin. Do you believe that natural bodybuilders should train differently than drug-assisted bodybuilders?

Brad Schoenfeld: There is, of course, no doubt that drug-assisted bodybuilders achieve significant training advantages compared to natural physique athletes. Taking exogenous anabolic hormones drives muscle protein synthesis, decreases catabolic processes, and fosters greater recovery allowing for a much greater volume and frequency of training.

Natural lifters must be much more cognizant of optimizing training volume without bringing about overtraining, and accomplishing this balance requires a delicate balance of manipulating training variables within one's abilities.

I don't necessarily agree that natural lifters need to work specific muscles more than once a week, however, at least on an ongoing basis. Anecdotally, I've achieved greatest success both personally and with high-level physique athletes using a periodized approach that alternates training frequency over the course of a 12-week mesocycle.

Training for each muscle group varies between one to two times per week, with periods of unloading interspersed throughout the training cycle to minimize overtraining potential.

T-Nation: Many bodybuilders utilize Joe Weider's "Instinctive Principle," which is in itself a form of periodization that relies on biofeedback. Mel Siff called this "auto-regulation" and described it as "Cybernetic Periodization."

Do you believe that most bodybuilders and powerlifters should stick to a set periodized routine and stick to the formula, or that most should ditch the periodization schemes and learn how to listen to their bodies and train accordingly?

Brad Schoenfeld: I'm a big proponent of periodization for achieving any exercise-related goal. It has been validated by research and I've used it very successfully over the years in hypertrophy programs.

That said, periodization in itself doesn't preclude instinctive aspects, and I know Mel considered this a very important topic. There is actually a growing body of research supporting the use of "flexible nonlinear periodization" where subjects are allowed to self-select training intensities based on how they feel on a particular training day.

But while I do think it's important to listen to your body and, if necessary, adjust training intensity on a particular day based on subjective feelings, it can potentially result in trainees adopting a "psychologically lazy" training approach.

I would counter that most hard-training athletes can and should adhere to a structured periodized protocol and only need to make adjustments occasionally during the course of a mesocycle. At least that's been my experience with high-level physique competitors.

T-Nation: Let's say I want my legs to grow as large as humanly possible. Should I just focus on getting stronger at heavy lower body lifts such as squats, deadlifts, and leg press, or should I incorporate isolation movements such as leg extensions and leg curls?

Brad Schoenfeld: Multi-joint movements such as squats, rows, and presses will activate the greatest amount of muscle mass, so they certainly should be staples in any training routine.

However, single joint movements do allow for better targeting of individual muscles and thus can be an important part of a hypertrophy-oriented routine. Realize that during multi-joint movement training, certain muscles will dominate over others, causing imbalanced growth.

Employing single joint movements allows one to enhance muscle development in otherwise "underworked" muscles while also improving muscular symmetry (which is as important for physique athletes as overall muscular size, if not more so).

T-Nation: Does there seem to be an optimal split in terms of maximizing strength and hypertrophy? Should we be performing full body workouts, lower body and upper body split workouts, pushing and pulling workouts, or body part split routines?

Brad Schoenfeld: There is a good deal of science behind using split routines in a hypertrophy training protocol. Recent research shows that when performing multi-set routines, greater than 72 hours may be necessary before training the same muscle group to allow for sufficient muscle repair.

A split routine has been shown to afford the ability to maintain total weekly training volume with fewer sets performed per training session and greater recovery afforded between sessions.

I don't believe there is an "optimal" split, however. Many different combinations can and do work very well. Based on my experience it's best to vary the split over the course of a periodized program. The primary consideration here is to make sure to avoid working the same muscle group when training on successive days as this can impair muscular repair.

Now this isn't as simple as it sounds. Realize that the sternal head of the pectorals are heavily involved in shoulder adduction movements (such as lat pulldowns), the short head of the biceps are heavily involved in chest flys, the triceps synergists in shoulder presses, etc.

You must pay heed to these kinesiological facts to avoid short-changing the recuperative process and thus impairing muscular gains.

T-Nation: Let's say I want to isolate a certain part of a muscle, for example the outer pecs or lower lats. Is this possible or just wishful thinking? Does a comprehensive hypertrophy program focus mostly on the basics or does it include a wide variety of exercises with various vectors and positions of maximal tension?

Brad Schoenfeld: First, there is really no such thing as "isolation" in resistance training. The human body simply doesn't work in a way that allows us to focus solely on one muscle without activating other synergists and stabilizers.

The best we can seek to do is to "target" a particular muscle or portion of a muscle to a greater degree vis a vis another muscle. Thus, applied anatomy should be a prime consideration when devising a hypertrophic routine.

The most common application of this concept is with muscles that have different attachment sites. Examples include the trapezius (which is divided into upper, middle, and lower regions) and the deltoids (which have anterior, medial, and posterior heads).

However, there also are regional differences within various muscles that can impact their response to exercise choice. Specifically, studies show that certain muscles are divided into neuromuscular components—distinct regions of muscle each of which is innervated by its own nerve branch—which potentially can be activated by utilizing different exercises and/or variations of exercises.

The sartorius, gracilis, rectus abdominis, biceps femoris and semitendinosus, for example, are all subdivided by one or more fibrous bands or inscriptions, with each compartment innervated by separate nerve branches.

Interestingly, both the gracilis and sartorius are composed of relatively short, in series fibers that terminate intrafascicularly, which refutes the belief that muscle fibers always span the entire origin to insertion.

The bottom line is that these architectural variances of muscle warrant the need to adopt a multi-planar, multi-angled approach to hypertrophy training utilizing a variety of different exercises over the course of periodized program.

As to the examples you cited, it would be wishful thinking to attempt to target the outer pecs since the fiber composition of the pectoralis major simply doesn't afford this ability.

The lower lats, on the other hand, can be targeted to some degree given that the fibers of the lats have multiple attachment sites (i.e., at the spine, scapula, pelvis and humerus). Because of these multiple attachments, the lat fibers are arranged in different directions, from almost perpendicular at the upper region, to almost parallel with the body in the lower region.

Since muscles are maximally stressed when an exercise moves directly in line with its fibers, the upper lats receive greater stress when performing wider grip pulldowns while the lower lat fibers are stressed more during closer grip pulldowns.

T-Nation: Are machines useful in the development of hypertrophy? What could a machine possibly do that a free weight exercise couldn't?

Brad Schoenfeld: Both machines and free weight movements have a place in a hypertrophy-oriented routine as they complement each other in terms of their strengths and weaknesses.

With respect to machines, they have a hypertrophic advantage over free weights in that they allow a lifter greater ability to target specific muscles. Free weight exercises involve the contribution of a significant number of synergists and stabilizer muscles that do not come into play when using machines.

Thus, there is greater stress on the target muscle when training on a machine, potentially allowing for greater muscular development of that muscle.

Now it's important to point out that the synergists and stabilizers substantially contribute to muscular hypertrophy, so a combination of both modalities is important to maximize the hypertrophic response.

T-Nation: Does there appear to be an optimal rep range for maximum hypertrophy? Is this range uniform depending on the muscle/muscle group? Many bodybuilders swear by higher rep ranges for the lower body.

Brad Schoenfeld: Based on the majority of literature and the physiological basis of hypertrophy training, a moderate rep range (65% to 85% of 1RM) seems to be ideal for maximizing the hypertrophic response.

This rep range allows for the use of weights that result in significant mechanical tension while also potentiating sufficient muscle damage and metabolic stress to augment myogenesis. I've had excellent success utilizing a step-loading protocol where intensity is systematically increased with this rep range over the course of a mesocycle, followed by a one week unloading cycle of low intensity training.

Now this shouldn't be interpreted to mean that an individual whose goal is to maximize hypertrophy should solely train in a moderate rep range. A periodized mesocycle of lower rep sets will help to afford the use of heavier weights during moderate rep training, thereby increasing mechanical tension during the hypertrophy phase of training.

And employing a mesocycle of higher rep sets can facilitate increasing the lactate threshold, facilitating a better ability to train through lactate buildup and thus increase the extent of metabolic stress during training.

T-Nation: What about rest time in between sets? Should we wait 30 seconds, a minute, two minutes, or five minutes before performing the next set of an exercise?

Brad Schoenfeld: A moderate rest interval of about one to two minutes between sets appears to be ideal for maximizing hypertrophy. This allows a lifter sufficient recuperation time to recover most of his/her strength for maintaining a high degree of mechanical tension.

In addition, it enhances the body's anabolic environment via increased metabolic stress and hypoxia, heightening the potential for increased muscular growth. Shorter rest intervals comprise mechanical tension while longer intervals don't generate much in the way of metabolic stress.

T-Nation: Do we need to go to failure on all of our sets or at least some of our sets?

Brad Schoenfeld: The evidence seems to suggest that training to failure is a necessary part of optimizing hypertrophy. Most bodybuilders have intuitively realized this and employ training to failure as an integral part of their routines.

Now the question then becomes how often should one go to failure, and the answer to this is less clear.

There is compelling evidence that persistent training to failure over time can lead to overtraining and thereby impair results. Given that the threshold for overtraining is dependent on multiple factors and varies from person to person, it is difficult to give a general recommendation on the subject.

My best advice here is to periodize and/or limit the number of sets that are taken to failure, basing specifics on individual response over time. Here is where being in tune with one's body is extremely important to optimize a hypertrophy-oriented protocol.

T-Nation: Last question Brad, what is something that will inspire me for my workout later on today? Thanks again for taking the time to conduct this interview.

Brad Schoenfeld: The best inspiration that I can give is that if you adopt a scientific approach to increasing muscle mass, you can push past plateaus and optimize your genetic potential. I've never met anyone who can't improve on their physique if they embrace scientific training principles.

Take Home Points, as we, the Editors, see Them: