Muscular Growth: How Does A Muscle Grow?
Let's get right into this and start with a segment from the Neuromuscular System series:
Muscle biopsies of serious weight trainers have shown that it was the size of the individual fibers within their muscles that was responsible for the abnormal muscle size and not the actual number of muscle fibers present.
...although extreme conditions may result in modest hyperplasia. This tells us that the formation of new muscle cells (hyperplasia) is, at most, likely to be only a minor factor in increasing muscle size. The mechanism responsible for supercompensation is hypertrophy - the increase in size of existing muscle fibers.
Taking another segment from the Neuromuscular System series:
It is also worthy of note that contractile machinery comprises about 80% of muscle fiber volume. The rest of the volume is accounted for by tissue that supplies energy to the muscle or is involved with the neural drive.
This tells us that there are a couple of ways to increase muscle size.
Increase the volume of the tissue that supplies energy to the muscle or is involved with the neural drive - called sarcoplasmic hypertrophy.
Increase the volume of contractile machinery - called sarcomere hypertrophy.
Let's take a look at both routes.
Increasing the volume of the tissue that supplies energy to the muscle or is involved with the neural drive: Intimately involved in the production of ATP are intracellular bodies called "mitochondria". Muscle fibers will adapt to high volume (and higher rep) training sessions by increasing the number of mitochondria in the cells. They will also increase the concentrations of the enzymes involved in the oxidative phosphorylation and anaerobic glycolysis mechanisms of energy production and increase the volume of sarcoplasmic fluid inside the cell (including glycogen) and also the fluid between the actual cells. This type of hypertrophy produces very little in the way of added strength but has profound effects on increasing strength-endurance (the ability to do reps with a certain weight) because it dramatically increases the muscles' ability to produce ATP. Adaptations of this sort are characteristic of Bodybuilders' muscles.
It should also be obvious that as the volume of the tissue that supplies energy to the muscle represents only around 20% of the total muscle cell volume in untrained individuals, this isn't where the real size potential lies.
Sarcoplasmic hypertrophy of muscle cells does directly produce moderate increases in size . But also, as you'll know from the Neuromuscular System series, ATP is the source of energy for all muscular contraction - type II fibers included. Wouldn't having more of this in the muscle, and having the ability to produce greater intramuscular quantities at any one time, be an asset? The answer is, cleary, "yes". That's where a major portion of the importance of sarcoplasmic hypertrophy comes into Bodybuilding. (We'll deal with training to produce this type of adaptation in an article on the 'Training Related Articles' page.)
As for increasing the tissue that is involved with the neural drive, this would theoretically occur in response to the need for contracting cells with hypertrophied contractile machinery. Directly, it would produce very little in the way of added size.
In addition, there are other intracellular bodies who's growth and/or proliferation would fall under the category of sarcoplasmic hypertrophy. These would be organelles such as the "ribosomes", which are involved in protein synthesis. As in the case of neural drive machinery, in most cases they would increase in size or number only to support sarcomere hypertrophy. They would have little direct impact on overall muscle size.
Increasing the volume of contractile machinery: The vast majority of the volume of each muscle cell (~80%) is made up of contractile machinery. Therefore, there lies the greatest potential for increasing muscle cell size. Trained muscle responds by increasing the number of actin/myosin filaments (sarcomeres) that it contains - this is what is responsible for increased strength and size. But before a muscle will grow like this it has to be "broken down". Let's take a look at both the "breaking down" and "building up" processes:
The Process Of Exercise-Induced Muscle Cell Damage
Actin/myosin filaments sustain "damage" during high-tension contractions. In addition, breaches in plasma membrane integrity allow calcium to leak into the muscle cells after training (there is much more calcium in the blood than in the muscle cells). This intracellular increase in calcium levels activates enzymes called "calpains" which "break off" pieces of the damaged contractile filaments (called "easily releasable myofilaments"). Following this, a protein called "ubiquitin" (which is present in all muscle cells) binds to the removed pieces of filaments thus "identifying" them for destructive purposes. At this time, neutrophils (a type of granular white blood cell that is highly destructive) are chemically attracted to the area and rapidly increase in number. They release toxins, including oxygen radicals, which increase membrane permeability and phagocytize (ingest and "destroy") the tissue debris that the calcium-mediated pathways released. Neutrophils don't remain around more than a day or two, but are complimented by the appearance of monocytes also attracted to the damaged area. Monocytes (a type of phagocytic cell) enter the damaged muscle and form into macrophages (another phagocytic cell) that also release toxins and phagocytize damaged tissue. Once the phagocytic stage commences, the damaged fibers are rapidly broken down by lysosomal proteases, free O2 radicals, and other substances produced by macrophages. As you can tell, the muscle is now in a weaker state than before it was trained. Incidently, macrophages have an essential role in initiating tissue repair. Unless damaged muscle is invaded by macrophages, activation of satellite cells and muscle repair does not occur.
Also, increased intracellular Ca++ concentrations are known to activate an enzyme called phospholipase A2. This enzyme releases arachidonic acid from the plasma membrane which is then formed into prostaglandins (primarily PGE2) and other eicosanoids that contribute to the degradative processes.
So, now that we've seen how the muscle gets damaged, how does it grow?
The Process Of Exercise-Induced Muscle Growth
It was mentioned in the The Neuromuscular System Part I: What A Weight Trainer Needs To Know About Muscle article that muscle cells have many nuclei and other intracellular organelles. This is because nuclei are intimately involved in the protein synthesis process (don't forget, actin and myosin are proteins), and a single nuclei can only support so much protein. If muscle cells didn't have multiple nuclei they would be very small muscle cells indeed. So if a muscle is to grow beyond its current size (i.e. synthesize contractile proteins - actin and myosin) it has to increase the number of nuclei that it has (called the "myonuclei number"). How does it do this? Well, around the muscle cells are "myogenic stem cells" called "satellite cells" (or "myoblasts"). Under the right conditions these cells become more "like" muscle cells and actually donate their nuclei to the muscle fibers (very nice of them). For this to happen, to any degree, several things need to take place. One, the number of satellite cells has to increase (called "proliferation"). Two, they have to become more "like" muscle cells (called "differentiation"). And three, they have to fuse with the needy muscle cells.
When the sarcolemma (the muscle cell wall) is "damaged" by tension (as in weight training or even stretching) growth factors are produced and released in the cell. There are several different types of growth factors. The most significant are:
Insulin-like Growth Factor 1 (IGF-1)
Fibroblast Growth Factor (FGF)
Transforming Growth Factor -Beta Superfamily (TGF-beta)
These growth factors can then leave the cell and go out into the surrounding area because sarcolemma permeabilty has been increased due to the "damage" done during contraction. Once outside the muscle cell these growth factors cause the satellite cells to proliferate (mainly FGF does this) and differentiate (mainly IGF-1 does this). TGF-beta actually inhibits growth - but everything can't be perfect. After this process the satellite cells then fuse with the muscle cells and donate their nuclei. The muscle cell can now grow.
So now factors that promote protein synthesis such as IGF-1, growth hormone (GH), testosterone and some prostaglandins can go to work. How does that all happen? Read on...
Protein synthesis occurs because a genetically-coded subtsance called "messenger RNA" (mRNA) is sent out from the nucleus and goes to organelles called "ribosomes". The mRNA contains the "instructions" for the ribosomes to synthesize proteins, and so the process of constructing contractile (actin and myosin) and structural proteins (for the other components of the cell) from the amino acids taken into the cell from the bloodstream is set off. Several substances can influence this process. A short overview of the major ones are found below:
IGF-1: IGF-1 comes in two varieties - actually, they are both the same molecule but come from different places. paracrine IGF-1 (also called "systemic" IGF-1) is made primarily in the liver and autocrine IGF-1 (also called "local" IGF-1) is made locally in other cells (it's called "local" IGF-1 because it isn't released in large quantities into the bloodstream - it stays in the area in which it was made). Cells don't let systemic IGF-1 in unless they want to (there are "picky" receptors on the cell wall) but the IGF-1 that was manufactured and released in the muscle cell as a response to the high tension contractions can do it's thing because it's already inside. So, once in the cell, IGF-1 interacts with calcium-activated enzymes and sets off a process that results in protein synthesis (and the calcium ions that were released during muscle contraction and also the ones that leak into the muscle after the sarcolemma is damaged by training ensure that the necessary enzymes are activated). A large part of this increase in protein synthesis rate is due to the fact that the IGF-1/calcium/enzyme complexes make protein synthesis at the ribosomes more efficient.
By the way, insulin works at the ribosome in a similar manner, hence the name insulin-like growth factor-1 (IGF-1). So get some quick digesting carbs in after your workout to raise insulin levels.
GH is thought to work, primarily, by causing the cells (muscle cells included) to release IGF-1.
Certain prostaglandins are released during contraction (and stretch); two of the most significant to growth being PGE2 and PGF2-alpha. PGE2 increases protein degradation, whereas PGF2-alpha increases protein synthesis. But PGE2 isn't all bad because it also powerfully induces satellite cell proliferation and infusion. The mechanism of PGF2-alpha's action is much less clear but is suspected to be connected to increasing protein synthesis 'efficiency' at the ribosomes also.
And the Granddaddy of them all: testosterone. "Free" testosterone (the kind that isn't bound to some other substance) travels freely across the muscle cell membrane and, once inside, activates what's called the "androgen receptor". "Bound" testosterone must first activate receptors on the cell surface before it can enter (the number of receptors on the surface is what controls this pathway). Once the androgen receptor is activated by testosterone it travels to the nucleus and sets off the protein synthesis process. In this way, testosterone directly causes protein synthesis and is, by far, the most powerful anabolic agent found naturally in the human body. Testosterone also increases the satellite cells' sensitivity to IGF-1 and FGF, thereby promoting satellite cell proliferation and differentiation. It also increases the body's systemic output of GH and IGF-1.
And, guess what, after a workout the muscle cells are more "receptive" to testosterone, systemic IGF-1 and GH - it's almost as if the muscle "knows" that it needs to grow.
In addition, there have also been some studies showing that the build-up of phosphates and hydrogen ions, that occurs as a muscle fatigues (see the Failure Muscular Fatigue During Weight Training article), may also contribute (directly or indirectly) to the growth process. The reasons, as of yet, are unknown.
The whole process of cellular damage and subsequent overcompensation (the cells grow back a little bigger than they were before) can take anywhere in the neighbourhood of 24 hours to several days - depending on the severity and type of training.
And You Though It Was Magic
Learn anything useful? Even if you don't realize it you probably did. Knowing the process can be an extremely useful tool when designing training programs.
Adams GR, McCue SA, Local infusion of IGF-1 results in skeletal muscle hypertrophy in rats. J. Appl. Physiol., 1998; 84(5): 1716-1722
Brooks, G.A., T.D. Fahey, T.P. White, and K.M. Baldwin. (2000). Exercise Physiology: Human Bioenergetics and Its Applications. Mountain View, CA: Mayfield Publishing.
Dunn SE, Burns JL, Michel RN. Calcineurin is required for skeletal muscle hypertrophy. J. Biol. Chem., 1999; 274(31):21908-21912.
Palmer RM. Prostaglandins and the control of muscle protein synthesis and degradation. Prostaglandins Leukot Essent Fatty Acids, 1990 Feb; 39(2):95-104
Robert K., Md Murray, et al. (1999). Harper's Biochemistry. McGraw-Hill Professional Publishing
Rooney KJ, Herbert RD, Balnave RJ. Fatigue contributes to the strength training stimulus. Med Sci Sports Exerc, 1994 Sep; 26(9):1160-4.
Rosenblatt JD, Yong D, Parry DJ, Satellite cell activity is required for hypertrophy of overloaded adult rat muscle. Muscle Nerve, 1994; 17:608-613.
Rosner W, Hryb DJ, Khan MS, et al. Androgens, estrogens, and second messengers. Steroids, 1998; 63:278-281.
Schott J. McCully K. Rutherford O.M. The role of metabolites in strength training. Eur-J-Appl-Physiol., 1995 71(4) P 337.
Spagnoli A, Rosenfeld RG. The mechanisms by which growth hormone brings about growth. The relative contributions of growth hormone and insulin-like growth factors. Endocrinol Metab Clin North Am, 1996 Sep; 25(3):615-31.
Thompson MG, Palmer RM. Signaling pathways regulating protein turnover in skeletal muscle. Cell Signal. 1998 Jan; 10(1):1-11.
Thompson SH, Boxhorn LK, Kong W, and Allen RE. Trenbolone alters the responsiveness of skeletal muscle satellite cells to fibroblast growth factor and insulin-like growth factor-I. Endocrinology, 1989, 124:2110-2117.
Vandenburgh HH, Shansky J, Solerssi R, Chromiak J. Mechanical stimulation of skeletal muscle increases prostaglandin F2 alpha production, cyclooxygenase activity, and cell growth by a pertussis toxin sensitive mechanism. J Cell Physiol, 1995 May; 163(2):285-94
Muscular Growth Part II: How Does A Muscle Grow?
Rational and Irrational Hypertrophy
In part one of this series I said that sarcoplasmic hypertrophy produces moderate increases in size but that there were other important reasons why you'd desire such adaptations. This is part of the reason I said that:
Metabolic processes within the cell require ATP to "fuel" them (remember, ATP is the body's primary source for all of its energy). If enough ATP isn't present then a host of cellular processes slow down (including protein synthesis) resulting in the operations of the cell being compromised. That means, among other things, slower removal of waste products, slower recovery from training and slower or less protein synthesis. Research done in the former Soviet Union by Zalessky and Burkhanov has shown that if the contractile components of the cell continue to grow (sarcomere hypertrophy) without a concurrent increase in the energy supplying systems of the cell (i.e. the mitochondria, etc. - sarcoplasmic hypertrophy) then such a situation will develop. Essentially the motor has become too big for the fuel injection system. In addition, fellow Soviet researchers, Nikituk and Samoilov have demonstrated that such a condition can be brought about through poorly planned training.
Once such a situation is achieved progess, as far as metabolic processes in the muscle is concerned, will come to a halt. Training may stimulate growth and strengthening but the cell simply lacks the means to support any additional hypertrophy. It can't produce the ATP necessary to fuel the synthesis and maintenance of new protein (muscle protein is constantly being broken down and rebuilt - a process of "maintenance"). In layman's terms, you hit one helluva plateau.
Such a condition is called irrational hypertrophy because the situation just doesn't make any sense from an adaptative standpoint. The defining characteristic of this kind of growth is cells that contain much larger mitochondria than before, but much fewer of them. The net result is an ATP shortage in the cell.
On the other hand, if training results in proportionate vascular improvements within the cell (mitochondrial density increases - the total number of mitochondria also increases as the existing mitochondria get bigger), such a plateau will not be encountered and training-invoked hypertrophy can continue as normal. This is called rational hypertrophy, for obvious reasons.
As this article isn't intended to get into the nitty-gritty of training procedures I'm just going to leave this subject by saying that for continued progress sarcoplasmic hypertrophy is, indeed, needed (especially when increased muscle mass and/or endurance is desired) and must be trained for. How to achieve rational hypertrophy, while avoiding the irrational kind, will be dealt with in other articles on this site.
"But Why Aren't Olympic Lifters Bigger Than Bodybuilders?"
It wouldn't be right not to address the fact, though, that training with weights ~90% of your 1RM and above seems to favor the development of strength and power more so than muscular size. But, in light of the information presented in Part I of this series, how is that possible? Well, it appears that an intense set of several reps may consistently recruit and train more fibers than an intense set of only 1 rep (this may also vary from muscle to muscle). It is also theorized that when using loads of ~90% of 1RM and above muscular failure may occur because of signaling problems at the neuromuscular junction, and that this occurs before a significant growth stimulus has been delivered to the cells.
Think of it like this: The total time that the muscle fibers are required to produce force is shorter in low-rep sets than in higher-rep sets and this may result in exhaustion of fewer muscle fibers and a lesser growth stimulus. Simply put, a hard set of 8 reps may deliver more growth stimulus to the muscle cells than a hard set of 3 reps because in a 3-rep set (or any low number of reps) failure may occur before a significant growth stimulus has been achieved.
In addition, when higher reps are performed substrates such as phosphate and hydrogen ions build up in the muscles - some researchers theorize that the presence of these substrates may further stimulate the muscular growth process. It is also widely believed that lifting heavy weights (~90% of 1RM and above) stimulates the nervous system to "improve" its firing pattern, frequency and efficiency to produce peak strength, making you stronger without actually increasing muscle size.
These reasons are why bodybuilders, as a group, have bigger muscles than Olympic lifters - they train with lighter weights, and perform higher reps. It also explains why Olympic lifters, as a group, are much stonger than bodybuilders, but not nearly as heavily muscled.
It also needs to be pointed out that any type of repetitive weight training (regardless of rep range) will result in the type IIB fibers having endurance-type adaptations. This occurs most quickly and profoundly at lighter loads (8-15 rep maximums) because, with these loads, the type IIBs do not twitch with maximum frequency and, therefore, start adapting to twitch at lower frequencies but for longer periods. When this happens the IIB fibers will be able to produce tension for long enough periods to incur substantial muscular damage and build up high concentrations of fatigue products. This gives the Bodybuilder more more material to work with in terms of muscle growth (in addition to the type IIA fibers themselves).
If you look closer at fiber recruitment patterns during sets in the higher rep ranges you'll see exactly how this happens: initially the IIAs are recruited and, perhaps, the IIBs also. As the IIAs fatigue more and more IIBs are recruited, gradually, to meet the force requirments. These IIBs are called upon to produce force for longer periods than they are biologically suited for. Training of this sort is actually endurance training for the IIB fibers, so they begin to adapt so that they have better endurance characteristics (i.e. higher mitochondrial densities and greater abilities to sustain enzyme concentrations).
Don't do as others have, and use these observations to argue that bigger muscles are not stronger muscles. As was eluded to above, muscles adapt very specifically to specific tasks. If you train using three rep sets then they get good at doing three rep sets. If you train using 8 rep sets then they get good at doing 8 rep sets. It just happens to be that years of empirical evidence has indicated that 8 rep sets stimulate more muscle growth than 3 rep sets (assuming of course, you are training with sufficient intensity). Make no mistake about it though, your legs will be bigger when you're squatting 405 for 8 than they were when you were squatting 275 for 8. For the case of 3 rep sets, you may not be much bigger when you're cleaning 315 for 3 than you were when you were cleaning 185 for 3, but you will have a much more efficient nervous system for the task.
Train for strength!
I don't mean to sound like a broken Mike Mentzer seminar record here, but if you want to get stronger OR bigger you MUST train for strength. If strength is your main concern you should train predominantly with lower reps - with ~85% of your 1RM and more. If it's muscular size you're after you should train with higher reps - with ~70% to ~85% of your 1RM. But getting stronger in the rep range that you're using should be your first and foremost goal.
If the above physiological arguments didn't convince you that you can't significantly increase the size of a muscle without it getting stronger ask yourself this question: Do you really believe that when you add 50 pounds to your barbell curls your biceps won't be bigger?