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The Science of Hypertrophy
Taking a new look at the “workout”

Introduction: Hypertrophy, simply stated, is an increase in muscle. Muscle cells are not like regular circular cells. Muscle cells are long and complicated and have several nuclei (brains of the cell). They are elongated with a fibrous interior full of little bands of contractile proteins that pull against each other to make muscles contract.. There are several ways to achieve hypertrophy. One way is to add more contractile proteins so the muscle is bigger and has more to pull with, making it stronger; however, only so much protein can be added before the muscle runs out of nuclei to control all the contractile proteins. In this case, muscles must actually recruit more nuclei, cellular organelles and proteins etc. from satellite cells. Satellite cells are essentially dormant in the body, waiting to be recruited to become a functional cell. They have no function until they are signaled to become something else, such as joining with other muscle cells to make a single, larger cell out of two merging cells.

Brief Physiology and Endocrinology
Your body has many ways to accomplish the above to things. It can release IGF-I (insulin like growth factor) both systemically and locally which causes the satellite cells to replicate, as well as, the relocation of some satellite cells to existing muscle cells by fusing with them, making them larger, and giving the ability to take on more contractile protein. Testosterone and other androgens can also cause satellite cells to replicate and relocate. They work by signaling androgen receptors on the satellite cells signaling them to replicate and fuse with muscle cells. Androgen receptors are unique in that, unlike most other receptors, androgen receptors actually increase in number with stimulation, making testosterone more effective over time. These receptors will drop down after a prolonged period or exposure to high levels of testosterone though. Lactic Acid is created during workouts as a bi product of creating energy. This is usually the cause of the burn, or soreness that follows shortly after a workout. Lactic acid signals the muscle and connective tissues for repair and in doing so also directly corresponds to an increase in HGH (human growth hormone). HGH is the body's main growth hormone. It signals the release of many other growth factors and metabolic regulators, so while it may not be directly affecting the muscle in the way that some of these other hormones do, HGH indirectly increases things such as IGF. Studies have also shown that in the absence of HGH the muscles while still containing the same number of fibers have significantly reduced muscle fiber width. MGF (mechano growth factor) and IGF-IEa are locally produced growth factors that are produced by the muscle itself. MGF is the main growth factor in replicating the satellite cells, it is the most important and most effective thing produced for increasing muscle satellite cells. IGF-IEa is its counterpart and is most effective at causing the satellite cells to fuse with muscle cells. MGF and IGF-IEa are released by muscles in response to stress and stretch stimulation. They are released in stages, MGF first and IGF-IEa a few days later. This allows for a natural process of regeneration of satellite cells, ensuring the population is never depleted. Depletion of satellite cells makes replenishing them harder because there are fewer cells replicating. These two growth factors are splice variants of IGF-I, together they are more effective than IGF-I but they are limited in that they can not cause hypertrophy themselves. However, IGF-I can signal the process of both of these, but not as effectively. The other difference is MGF and IGF-IEa are produced locally and do not effect other parts of the body where as IGF-I is a systemic growth factor mainly produced by the liver that effects many other parts of the body. There are also things that our body does to limit hypertrophy and/or induce atrophy (muscle wasting). Some training methods, although they up-regulate several of the hypertrophy inducing factors, actually stimulate some of the limiting and atrophy inducing factors. One hot topic is Myostatin. Myostatin is a protein produced by the body that keeps the muscle stem cells from replicating. This counteracts the positive effects of growth factors like IGF and hormones like testosterone. Another way that the body can prevent hypertrophy is through a rapamycin. Rapamycin blocks the hypertrophy signaling that is brought about by the activation of the AKT pathway and down stream regulators that are up-regulated by IGF. So it prevents some effects of training and IGF.
Angiotensin II is a factor that down regulates AKT, reduces circulating IGF levels and increases protein breakdown and programmed cell death in muscle tissue. Limiting any expression of this factor is extremely valuable. It seems that stimulation of IGF combats the effects of Angiotensin II as well.

In vivo research studies
The Basic Rep
Each repetition of an exercise consist of two motions. The eccentric (lowering or un-contracting) and the concentric (raising or contracting). Studies have shown that performed individually concentric training yields a greater gain in muscle size, soreness, and creatine kinase activities. Eccentric training yields greater range of motion, and maximum isolation strength. The amount of tissue damage is significantly greater during the eccentric portion of the rep. Taken together in the proper ratio of emphasis using tempo lifts such as a 2 sec contraction and a 1 second eccentric motion for example can provide optimal increase in muscle size and strength. It is important to note that while the eccentric training may not yield immediate gains in mass, the damage induced repair will lead to increased muscle cell nuclei giving it a higher potential for further growth. This is because the stretch and stress will increase MGF and IGF-IEa in the muscles worked. So the importance of the negative portion of a rep can not be underestimated.

How Many Sets?
Studies show that when comparing a single max effort set of 10 reps after warm up compared to that of a set of 6 reps yielded very different results. Androgen receptors were up-regulated greater in the single set group, in fact there was a 46% drop in androgen receptor content at 1 hour post exercise in the 6 rep group. However the 6 rep group showed a 12-23% increase in testosterone levels post exercise. Thus further research has shown that between these extremes in the 2-3 rep range with proper intensity you can up-regulate both testosterone levels and the androgen receptors with less muscle damage creating a much more anabolic environment. In addition to testosterone studies have shown that when comparing 2 vs 4 sets of an exercise, the 4 sets resulting in increased cortisol levels and HGH levels after muscle hypertrophy (1-RM), 3-min rest) and MH (10 reps at 75% of 1-RM, 2-min rest) and strength endurance training(15 reps at 60% of 1-RM, 1-min rest). There were no differences between muscular strength or testosterone levels between these two groups. Further research would suggest that because of the time length and repeated isolation of the same muscles only cortisol levels began to increase accordingly. By reducing either the time frame or number of sets the HGH./cortisol level may have been more favorable. Spending 12-18 minutes on one exercise is not a good idea. GTP utilizes a method of reps and sets to achieve the HGH stimulation without causing a cortisol increase as seen here.
In addition one must consider the effects of exercise induced damage in high set workouts. It does not take a lot to achieve enough muscle damage to signal repair. Research shows that a few skeletal muscle adaptation can be brought about by a single bout of relatively few eccentric muscle contractions. Increasing the number of eccentric muscle repetitions did not result in an increased prophylactic effect on skeletal muscle. Furthermore adaptation to eccentric exercise can occur in the absence of significant muscle damage. Exposure to a small number of non-damaging eccentric contractions can significantly improve recovery after a subsequent damaging eccentric bout. However this adaptation appears to be mode-specific and not applicable to concentric contractions.
In conclusion the cellular response for growth from muscle damage is directly related to creatine kinase levels which do not increase with further muscle damage by repeated eccentric sets.

How often/ training frequency
Training frequency has been discussed among athletes for quite some time. Research shows that while everyday training actually increases anti-hypertrophy factors and increase in myostatin levels, 48 hours in between sessions provides a steady anabolic environment. Serum testosterone levels, the free androgen index, Androgen receptor mRNA and protein were significantly increased. No negative factors were found to be increased in this study. With more than 48 hours between exercise sessions these levels begin to decline fast. This study used 3 sets of the exercise, and took data after 3 sessions each 48 hours apart.

©Flawless Training 2006 All Rights Reserved

©Flawless Training 2006 All Rights Reserved

Rating the Other Workout Routines

HST Hypertrophy Specific Training
Benefits: Utilizes optimum training frequency, fairly good stimulation of testosterone and androgen receptors and protein turn over. Low chance of increasing cortisol levels, does not cause unnecessary muscle damage. Moderate IGF-I stimulation.
Flaws: Fails to utilize HGH and lactic acid induced hypertrophy, limited MGF/IGF-IEa stimulation.

DC Training
Benefits: Utilizes HGH and lactic acid pathways to hypertrophy very well. Good at increasing testosterone. Stimulates MGF and IGF-IEa pathways. Burns a lot of calories.
Flaws: High likelihood of increased cortisol. Detrimental to androgen receptor content. Significant muscle damage can occur achieving your goal leading to increased risk of injury and limits in strength. Fails to keep the body in an anabolic state with time through training frequency.

Traditional Upper/ Lower Body Split (M T TH F routines)
Benefits: Generally utilizes HGH and lactic acid, provides stimulation for MGF and IGF-IEa somewhere between HST and DC. Better frequency than DC training, resulting in a more steady anabolic state but not as good as HST. Moderate to good testosterone stimulation.
Flaws: Slightly less likely to increase cortisol than DC, and prone to decreased androgen receptor content. In between Dc and HST on muscle damage.

The Once Per Week for Each Body part Routine
Benefits: Good testosterone stimulation and HGH/lactic acid stimulation. Muscle damage is likely but optimal time for repair if muscle damage is moderate. Good MGF stimulation.
Flaws: Very short term anabolic state for growth to occur. What stimulation there is, is short lived. Often times has high cortisol levels and decreased androgen receptors associated. While there may be optimal time for muscle repair, connective tissue damage may not be able to repair at a rate that is safe.

HIT High Intensity Training
Benefits: No muscle Damage issue. Not time consuming. No increase in cortisol levels. No negative effect on androgen receptor content.
Flaws: Poor increase in testosterone and practically no increase in HGH or lactic acid levels. Limited MGF stimulation.

GTP Games Training Protocol
Benefits: Almost equal stimulation of HGH and lactic acid hypertrophy pathways without increasing muscle damage or cortisol levels. Significantly increased testosterone and androgen receptor content. Very good stimulation of MGF and IGF-IEa.
Flaws: Workout is demanding and intense.

©Flawless Training 2006 All Rights Reserved
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