HOW MUSCLES GROW – A BRIEF YET TECHNNICAL OVERVIEW

This is the first of a two-part series that will focus on the factors and mechanisms that help muscles grow.  The next issue will focus on what you can do that has been proven to aid in muscle growth.

The frailty of old age has emerged as an important public health problem because it impacts mobility, quality of life, and substantially increases the use of health care resources.  There is growing interest in the use of interventions for augmenting muscle mass and function to improve sarcopenia, the degenerative loss of muscle mass and strength.  Researching and understanding the biological mechanisms of muscle growth is important to reach this goal.

Aw heck, muscle just looks good too.

Skeletal muscles are generally composed of two types of fibers: type I (slow twitch) and type II (fast twitch).  The average person has equal portions of both.  Someone with 80% type I would make a good marathoner, while those with 80% type II make great sprinters.  In order to add muscle mass, 1)  existing muscle fibers must increase protein synthesis, and 2) new muscle cells must be created from cells that are not muscle, but turn into and fuse with muscle.  These are called satellite cells.

Protein Synthesis:

One of the body’s main protein synthesis regulators is a gene in the nucleus of muscle cells named mTOR.  mTOR is signaled to stimulate protein synthesis in the presence of adequate levels of two substances:  ATP and leucine.  ATP is the main energy source of cells at the molecular level.  Leucine is one of three branched-chain amino acids.  Amino acids are the building blocks of protein.  If either ATP or leucine is not present in adequate amounts, mTOR will not stimulate protein synthesis.  Interestingly, intracellular ATP is increased with the supplement creatine, and the highest concentrations of leucine are found in the form of whey protein.  More on this in the next issue. 

Satellite Cells:

Satellite cells are stem cells (yes, stem cells) that are present beside normal muscle cells, and in undamaged muscle, are quiescent.  When activated, these cells multiply and change into cells called myotubes, which then fuse to existing muscle cells to make them bigger and stronger.  Satellite cell number is not constant throughout life and is dependent on age (decreased with age) and muscle fiber type (higher in type II).  Individual muscles vary in satellite cell population.

So what regulates satellite cells and protein synthesis?  In short, muscle loading and growth factors do.  Stimulating muscle through training increases both protein synthesis and satellite number.  We’ll learn more with the next issue – let’s move on to growth factors.

IGF-1:

If you’ve read previous issues of Lake Mary Life,  you’ll recall how much I’ve discussed insulin-like growth factor-1 and its positive role in many health processes, and muscle growth is no exception.  Recent research has further illustrated how remarkable the body can be in conserving and focusing the actions of IGF-1 in damaged muscle.  IGF-1 is mainly transported in the body as part of a 3-part complex:  IGF-1, a binding protein, and the acid-labile subunit (ALS).  IGF-1 cannot act when it is bound in this ternary complex, but when circulating in a more acidic environment, such as a muscle that is building up lactic acid because it is being exercised,  it breaks away from the complex and takes action locally in that muscle.

The gene that makes IGF-1 is also present in muscle cells.  After resistance training muscle damage, the IGF-1 gene is spliced to produce two hormones, mechano growth factor (MGF) and IGF-1Ea.  The initial pulse of MGF expression following muscle damage activates satellite cells, and is followed by later expression if IGF-1Ea to maintain protein synthesis to complete muscle repair.

Androgens:

Androgens are the grand-daddy of all muscle promoting factors.  They upregulate nearly all protein synthesis genes.  Satellite cells are believed to be a direct target of androgens because they express androgen receptors.  Testosterone also increases satellite cell number, and increases the number of androgen receptors on both muscle cells and satellite cells in a dose-dependent manner.  Androgens can recruit stem cells from other parts of the body that are not muscle and commit them into being muscle building precursor cells.  Androgens also increase MGF and IGF-1Ea expression.

Myostatin (boo, hiss):

Myostatin is a hormone that inhibits satellite cell number and transformation into muscle.  There is no relationship between testosterone levels and myostatin levels.  Some athletes and other remarkably strong people have been found to carry one mutant myostatin gene.  Anything that lowers the level of myostatin also leads to an increase in muscle fiber size.

There is a lot of interest in developing substances that inhibit myostatin, and well as block the action of cortisol, another hormone known to diminish muscle growth.  There are a lot of products for sale that claim they can do this and increase muscle mass.  Have there been any studies to prove this?  No!  **(update 6/25/09  Phosphatidylserine and Vitamin C have been shown to block increases in cortisol.)

Part II:

The following are summaries of well designed studies that can help you decide how to best maintain and build muscle mass.  Many products that are sold in health food stores and featured in muscle magazines are not mentioned because they have failed to demonstrate gains beyond placebo.

RESISTANCE EXERCISE

• Performing 3 sets of a resistance exercise has repeatedly been shown to yield more mass and strength gains compared to one set.  (Despite continued research, I have yet to find studies showing that doing more than 3 sets yields even better gains).

• Performing sets of 3-5 repetitions to near failure seems to yield better gains in strength;  7-9 repetitions is slightly better for muscular hypertrophy;  over 12 reps for better endurance.

• Muscular gains are greater when working a muscle group twice per week as compared to once weekly.

• There has been no definitive evidence that working a muscle to failure yields better gains than near-failure.

• Resting 2 minutes between sets yields the same muscle building effects as resting 5 minutes between sets.

NUTRITION

• Carbohydrate intake during training results in greater muscle gains and performance than no carbs.

• Carbohydrate plus protein intake around the time of training results in greater gains than an equal calorie amount of carbohydrate alone.

• Carbs plus protein plus leucine (an important amino acid) results in greater gains than carbs plus equal amount of total protein.

• Whey protein shows a slight advantage over soy protein and other dietary proteins for muscle gain.  (Whey has the highest percentage of the muscle promoting amino acid, leucine).

• Suggested daily protein intake for training is 1.5 gr/kg of ideal body weight.  There have not been any controlled studies to prove that more than this will yield healthier results.  For the average 175 pound man, that would come out to about 120 grams of protein per day.

• Five grams of creatine daily has shown mixed results for muscle mass and strength.  About 25% of men who train will be definite responders, 50% will be partial responders, and 25% will be nonresponders.

NUTRIENT TIMING

• A carbohydrate and protein supplement taken immediately before and after resistance training yields greater gains than if that same supplement is taken in the morning and evening.

TESTOSTERONE

• There is a direct relationship between testosterone levels and muscle mass gains with training.  Blood testosterone levels of 800 will yield better gains than levels of 300, even though both levels are considered within normal limits for an adult male.

OTHER PEARLS OF MUSCLE BUILDING WISDOM

• Ingestion of anti-inflammatory medication after exercise blunts the increase of satellite cells, which are an important component of building muscle cells.

• Aerobic exercise performed before resistance training will decrease the beneficial release of growth hormone normally seen, especially if the aerobic exercise is performed within 30 minutes of the start of the resistance training.

• The following supplements have not been shown to have any beneficial muscle enhancing effects over placebo:  arginine, glutamine, nitric oxide stimulators, caffeine, chromium picolinate, tribulus, chrysin, bicarbonate, ribose, DHEA, androstenedione, HMB, myostatin inhibitors, ZMA