If you want to build
muscle, it’s important to familiarize yourself with the following equations:
1.
Net Muscle Protein Balance (NMPB) = protein synthesis vs.
protein breakdown = *hypertrophy
2.
Energy Balance = calories in vs. calories out = weight gain/loss
*Hypertrophy = the
increase in muscle fiber size due to an accumulation of contractile and
non-contractile proteins inside the cell
The second equation
is one that many who’ve sought to lose weight are familiar with. It suggests
that if you want to lose weight, than you need to burn more calories than you
are taking in. Unfortunately it’s not that simple, as the hormonal response
from different foods can prevent you from losing weight, even in a restricted
state, but that’s another topic for another time.
The first equation
suggests that if you want to build muscle, your body needs to be in a state of
a positive NMPB for a greater amount of time than it is either in an equal, or
a negative NMPB. The greater positive NMPB, the more muscle will be built. Increasing
protein synthesis, decreasing protein breakdown, or a combination of both,
increases the likelihood of your body turning the food you eat into muscle! So
the million dollar question becomes, ‘how do you maximize protein synthesis,
while minimizing protein breakdown’?
The answer to that
is multi-faceted, as there are many contributing factors that need to be
addressed. The following is by no means a complete list, but is a good start in
terms of the most important variables responsible for maximizing protein
synthesis:
Satellite cells
Post-workout
nutrition
Energy balance
AMPK-mTOR
Testosterone (T)
Cortisol (C)
Growth Hormone (GH)
IGF-1
Insulin
Protein
Timing
Cell Volume
Glutamine
Each of these
factors can be influenced so that you’re putting yourself in the best position
to add as much lean muscle to your frame as your body will allow.
The first thing that
one needs to understand is the basic physiology of muscle cells, so that they
can consciously make the best decisions throughout the day to achieve their
muscle building goals.
Before anything
else, it is important to point out that the body is between 40-45% muscle, and
muscle is between 70-75% water, and 20-25% protein. To quantify those numbers,
a 180 lb. male (depending on bodyfat percentage) is roughly 72-81 lbs. of
muscle, to which 50.4-60.75 lbs. of it is water, and 14.4-20.25 lbs. of it is
protein, thus highlighting the importance of both water and protein if being
healthy is important to you, let alone maintaining/building muscle. Without
adequate protein and water consumption, you will not build as much muscle as
you could if you were ingesting enough protein and water. So if you want to
build muscle, you should start there.
Brief rundown of
muscle physiology
Muscle cells are
multinucleated cells (have more than one nucleus), unlike most body cells which
are mononucleated (have only one nucleus). A muscle fiber may have between
250-300 myonuclei per millimetre, indicating that there is a
cytoplasm-to-myonucleus ratio. Each myonucleus regulates gene transcription and
manages the production of mRNA and protein synthesis for a specific volume
within the cell. Hypertrophy beyond 17-25% may put each myonucleus under
greater strain, thus increasing the demand for new myonuclei to make continued
growth possible. This implies that increases in muscle size must be associated
with a proportional increase in myonucleus number, which poses quite the
problem since muscle cells are incapable of producing additional myonuclei.
Enter the need for
satellite cells
Skeletal muscle
contains a population of satellite cells, which have stem cell-like properties
enabling them to self-renew, and serve as reserve cells that are recruited when
muscular growth (by fusing to existing muscle fibers and donating the nucleus)
or regeneration (after injury) is needed. Satellite cells are activated in
response to signals associated with muscle damage and mechanical tension, and
migrate to the site of injury to repair or replace damaged muscles. If it weren’t
for satellite cells donating their nucleus, hypertrophy would be very limited.
The tension provided
by strength training stimulates the release of growth factors such as IGF-1 and
MGF. IGF-1 is a potent activator of satellite cells, as well as the mTOR (mammalian
target of rapamycin) signalling pathway, which is a key regulator in protein
synthesis (more on that later).
The effects on NMPB
post-workout
The difference
between protein synthesis and protein breakdown is termed the Net Muscle
Protein Balance (NMPB), as stated above. The processes of synthesis and
breakdown of proteins are constant and concurrent, but NMPB will fluctuate
throughout the day depending on the exercise and feeding situation. After
eating, a rise in anabolic signals will result in rates of protein synthesis
exceeding rates of protein breakdown, resulting in a positive NMPB where the
muscle will be in a state of anabolism.
On the other hand,
during periods of fasting, rates of protein breakdown will exceed rates of
protein synthesis, NMPB will become negative and the muscle will be in a
catabolic state. Thus, over time, the mass of the musculature will reflect the
duration and magnitude of the respective periods of positive and negative NMPB.
After a workout,
signalling pathways regulate changes in protein synthesis and breakdown.
Protein synthesis is reduced during the initial recovery period after a
workout, but there is a marked increase after contraction-related ATP
requirements are back to baseline levels. Protein synthesis is doubled between
12-24 hours after the workout, and can remain elevated above baseline values
for up to 72 hours, depending on the intensity of the workout (loads above 60%
of max are typically needed, and above 80% for more experienced lifters).
Like protein
synthesis, protein breakdown is also elevated (25-50% above baseline levels)
after working out, especially in those who went a long time without eating
(fasted) before the workout. Protein breakdown peaks approximately 3 hours
after the workout, before declining, and stays elevated for a far shorter
period compared to protein synthesis, returning to baseline levels within 24
hours.
The rate of protein
synthesis in the post workout period is greatly influenced on the fed state of
the individual, more so than the rate of protein breakdown. Protein synthesis
will generally exceed protein breakdown if the individual is fed either before,
during, or immediately after exercise, where as breakdown will likely exceed
synthesis if the individual is fasted.
As far as dosage,
consuming roughly ¼ gram/kg of bodyweight of protein is ideal, and protein
synthesis will be doubled compared to fasted, and anything more may not
increase protein synthesis further as there is a ceiling effect.
Worth noting is the
overall volume of the workout may in fact influence the rate of synthesis
compared to rate of breakdown. Theoretically speaking, the more repetitions
that are performed during the workout, the greater the protein breakdown that
will be.
The importance of
energy balance
Protein has always
been the focus for increasing muscle mass and strength, but a more important
factor is total energy balance. A negative energy balance (in which more
calories are burned than are ingested) should be avoided if maximal hypertrophy
is the goal. Inducing a state of negative energy balance through dietary
restriction and exercise induces a state negative nitrogen balance which is
indicative of muscle loss. When energy balance is maintained however, muscle
mass may be gained regardless of how many grams of protein is taken per day.
Protein intake may
be more important for maintenance of muscle mass during reduced energy intake
combined with maintenance of training intensity and volume.
AMPK-mTOR signalling
pathways
The major regulator
in protein synthesis in response to exercise is the AMPK-mTOR signalling
system. mTOR is a gene that regulates the synthesis of proteins, which means
that the greater expression of mTOR, the greater level of protein synthesis.
Not only does mTOR stimulate many steps that lead to an upregulation of protein
synthesis, but also regulates the capacity for protein synthesis by producing
more ribosomes, which are the cellular machines that synthesize protein.
mTOR is activated by
IGF-1, MGF and phospholipase-D in response to strength training, and also
activated by insulin and amino acids, primarily leucine (more on that later).
AMPK has opposite
effects of mTOR and reduces protein synthesis and therefore muscle growth. It
is however associated with pathways involved in carbohydrate and fatty acid
metabolism, which is beneficial for fat loss. AMPK is activated by AMP which
increases during exercise, and by low glycogen (glycogen content decreases
during exercise).
These distinct genes
and signalling pathways that have conflicting actions, and are activated or
suppressed in response to endurance and strength related exercise.
Hormones
Hormones play a role
in the muscle building process by regulating protein turnover. Mechanical
tension is known to stimulate acute changes in hormone concentrations, which
are thought to mediate those cellular processes involved in muscle growth.
Testosterone (T)
T is thought to
contribute directly to muscle protein and glycogen synthesis, whilst also
reducing muscle protein breakdown, thus having an important anabolic effect
upon muscle tissue growth. Indirectly T may also stimulate the release of other
anabolic hormones (GH, IGF-1) important for muscle tissue growth.
Hypertrophy
protocols (high volume, incomplete rest intervals) typically have the greatest
T response, however levels are inversely proportionate to the duration of the
workout, meaning that the longer the workout goes on for, the lesser T
response.
Cortisol (C)
C is regarded as the
primary catabolic hormone as it decreases protein synthesis, and increases
protein breakdown. C is a major glucocorticoid and has an important role in
metabolism and immune function. The release of C is stimulated by
adrenocorticotrophic hormone (ACTH), which is over secreted in response to the
increased sensitivity of the hypothalamus-pituitary axis (HPA) to stress. The
rise in C occurs roughly 15-30 minutes after ACTH is released.
In metabolism, C
causes increases in protein degradation in muscle and connective tissue, amino
acid transport into the liver, liver glycogen synthesis, gluconeogenesis (which
results in the sparing of blood sugar and protein stores), and lipolysis.
On the flip side, C
reduces protein synthesis, amino acid transport to muscle, and glucose uptake
and utilization.
As with
testosterone, hypertrophy protocols elicit the greatest C response, probably
due to the volume (sets X reps) which contributes to overall stress levels on
the body. The longer the workout goes on for, the greater C response, which is
why many strength and conditioning experts suggest limiting your workouts to no
more than one hour.
Testosterone:Cortisol
Ratio
Both cortisol and
testosterone are made from the same raw material (pregnenolone), so minimizing
stress, or anything that could lead to elevated levels of cortisol during parts
of the day that don’t require it to be elevated, is in your best interest to
create the most anabolic internal environment from a hormonal standpoint.
Growth Hormone (GH)
Unlike steroid
hormones (T and C amongst others) GH represents a family of proteins (over 100
molecular isoforms have been identified), rather than a single hormone complex.
GH influences muscle growth by increasing protein synthesis by facilitating
amino acid transport, and reducing muscle protein breakdown, increasing the
metabolism of glucose, as well as by stimulating the release of a family of
polypeptides from the liver which are known for their anabolic effects upon
muscle tissue (ex. by mediating the production of IGF-1). GH is also lipolytic
(stimulates lipolysis), therefore improving body composition!
Like T and C,
hypertrophy protocols seem to elicit the greatest GH response.
IGF-1
IGF-1 is a
polypeptide hormone with structural similarities to insulin, produced by the
liver, and plays a key role in mediating metabolic and anabolic responses
during altered energy states. It also has a role in bone and muscle anabolism
among many other physiological processes.
MGF, which is one of
IGF-1’s isoforms, is preferentially upregulated in response to mechanical
signalling 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 [a form of cell
signalling in which a cell secretes a hormone or chemical messenger that binds
to autocrine receptors on the same cell (auto), a cell nearby (para), leading
to changes in the cell] 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.
IGF-1 also mediates
the actions of GH – IGF-1 is to GH, what insulin is to carbohydrates.
Insulin
Insulin is believed
to have a strong anabolic effect upon muscle growth, repair and recovery. The
actions of insulin mediate the adaptive processors involved in tissue
regeneration and growth, whereas other anabolic hormones directly influence
cellular reactions and protein accretion, by either binding directly inside the
cell (steroid hormones, ex. T and/or C), or on the outside to the cell membrane
(peptide hormones, ex. GH).
Protein
Roughly 65% of the
body’s protein is found within skeletal muscle, and as stated above, muscle is
made up of 20-25% protein. The synthesis of new proteins following strength
training involves the incorporation of amino acids into proteins primarily
involved in muscle contraction (actin and myosin AKA myofibrillar proteins)
which make up roughly 80% of all muscle protein.
The synthesis of new
proteins occurs when signals within the muscle stimulate the assembly of a
specific sequence of amino acids into a chain, which eventually forms the new
protein.
BCAA’s are
associated with increased muscle protein synthesis and decreased protein
breakdown. Leucine, in particular, stimulates the anabolic signalling pathways
in the muscle that lead to muscle protein synthesis. Leucine is an insulin
secretagogue (a substance that causes another substance to be secreted) and the
hyperinsulinemia (a condition in which there are excess levels of circulating
insulin in the blood) elicited by leucine ingestion is what attenuates
(reduces) rates of protein breakdown.
Timing
The acute protein
synthetic response is dependent on the type and amount of protein ingested, the
timing of protein consumption in relation to the workout, and co-ingestion of
other nutrients (ex. carbohydrates), in addition to the type of workout itself.
Carbohydrates
The influence of
carbohydrates on NMPB is likely due to the resulting insulin response. At rest,
insulin stimulates anabolic signalling processes and can stimulate increases in
protein synthesis provided amino acid availability is maintained. This means,
the ingestion of carbohydrates, which elicits increases in plasma insulin, may
be beneficial to the anabolic response. Insulin also increases total blood
flow, redistributes blood to the muscle bed, and therefore also increases amino
acid delivery and uptake into skeletal muscle. However, large increases in
muscle protein synthesis occur with amino acid ingestion in the presence of low
insulin concentrations. Therefore, carbohydrate ingestion coupled to large
elevations in circulating insulin does not appear to be imperative for large
increases in muscle protein synthesis.
Moderate increases
in insulin increase NMPB in the period after exercise by reducing protein
breakdown. An attenuation of muscle protein breakdown will further improve
NMPB, leading to muscle protein accretion. Therefore, although the addition of
a small/moderate amount of carbohydrate to the ingestion of an amino acid
source after exercise may have little effect upon rates of muscle protein
synthesis per se, improvements in NMPB may occur through the inhibition of
protein breakdown.
Cell Volume
Adequate hydration
can result in the cells swelling AKA volumizing, which causes the cell to grow
because, as the liquid exerts pressure against the cell wall, it’s perceived as
a threat to cellular integrity to which the cell responds by reinforcing its
structure (i.e. growth). Cell swelling (intracellular hydration) inhibits
protein breakdown, stimulates protein synthesis, as cell volume is the main
driver of amino acid transport, also stimulating glycogen synthesis, and
activating mTOR, thus creating an anabolic environment by positively affecting
NMPB.
The role of
glutamine in getting leucine into the cell to turn on protein synthesis
While leucine is
required to activate mTOR, all the leucine in the world is of little value if
it can’t get into the cell in the first place to activate the gene. So the real
question now becomes, ‘how do we get leucine into the cells’?
Glutamine is
necessary for cell volumization, priming muscles for glycogen synthesis, while
inhibiting protein breakdown, and most importantly, is required for leucine to
get into the cell to activate mTOR through the tertiary active transport
system. In contrast, glutamine depletion results in a reduction of cell volume,
and a reduced ability of leucine to activate protein synthesis.
Membrane-bound ion
channels and transport proteins regulate what gets in and out of the cell. It’s
the transport proteins that enable leucine to get into the cell and turn on
protein synthesis. Here’s how the tertiary active transport system works:
The sodium potassium
pump (membrane bound pump) uses ATP to move 2 potassium ions into the cell, and
3 sodium ions out of the cell. The increased concentration of sodium outside
the cell activates a specific transport protein that couples sodium with
glutamine causing an influx back into the cell, which brings in water as well,
causing the cell to swell, putting it into an anabolic state, priming the
protein synthesis machinery for activation. When glutamine builds to
sufficiently high levels inside the cell a different transport protein is activated,
which shuttles glutamine out of the cell in exchange for leucine which is the
trigger for protein synthesis.
Other relevant roles
of glutamine
Glutamine is
considered the fuel of the immune system because it is so rapidly taken up by
immune cells, and intense workouts cause glutamine depletion. After a workout,
an inflammatory response is mounted, which allows immune cells to traffic into
muscle tissue to begin the repair/rebuild process. This is why glutamine
requirements are increased after a workout, where the local immune response may
be competing for the availability of glutamine to prime muscle cells for amino
acid uptake and protein synthesis.
HOW TO PRACTICALLY
APPLY ALL THIS INFORMATION TO MAKE YOUR CELLS GROW AS LARGE AS HUMANLY POSSIBLE
As stated earlier,
if you can manipulate each of the above factors in your favour you’re putting
yourself in a damn good position to add as much lean muscle to your frame as
your body will allow. Here’s a brief summary of how you can do that.
1. The
absolute most important thing you can do is to make sure you ingest more
calories each day than you burn, to create a positive energy balance. It’s that
simple; if you don’t eat at least as many calories as you burn, you will NOT
build more muscle than you already have, even if all your nutrients come from
protein.
2. Because
the rate of protein synthesis in the post workout period is greatly influenced
on the fed state of the individual, eating frequently to consistently give rise
to anabolic signalling, and preventing periods of fasting in which rates of
protein breakdown will exceed rates of protein synthesis, is advised.
3. As
far as the AMPK-mTOR signalling pathways are concerned, there are a few choices
you are in control of making to ensure that mTOR expression is maximized, and
AMPK expression is minimized. Providing your body with amino acid and
carbohydrate intake before, during, and after training, blunts AMPK mediated
inhibition of mTOR, as well as increasing the expression of the transport proteins
involved in getting leucine into the cell, priming the cell for maximum amino
acid uptake and activation of protein synthesis. As far as training parameters
are concerned, mTOR starts to be inhibited after 60 seconds of continuous
tension during a set, and workouts that go beyond one hour (possibly due to
glycogen depletion which increases AMP, and therefore activates AMPK, and then
inhibits mTOR). Therefore, since full recovery between sets will reduce
metabolic demand and enable you to give maximal effort and produce maximal
tension every set, full recovery between sets reduces metabolic demand and
enable you to give maximal effort and produce maximal tension every set.
4. Aside
from the positive effect on the AMPK and mTOR signalling pathways as it relates
to protein synthesis, amino acid and carb consumption also causes more of the
transport proteins responsible for getting glutamine into the cell to be
displayed on the cell membrane ready to drive more glutamine into the cell,
resulting in more cell volume, which drives more leucine into the cell,
ultimately leading to more protein synthesis. While protein consumption
increases the expression of transport proteins, insulin allows them to be
displayed on the cell surface, ready to shuttle new amino acids into the cell.
Insulin increases the capacity for cellular amino acid transport.
5. As
for the major anabolic hormones are concerned, hypertrophy protocols seem to be
ideal to maximize all of them (T, GH, IGF-1) the most (which is perhaps why bodybuilders
display the greatest amounts of hypertrophy out of all strength trained
athletes). The duration of the workout however can ultimately influence how
much of an anabolic response you will get, as the longer the workout goes on,
the greater the cortisol response (along with AMPK becoming increasingly
expressed), therefore reducing the anabolic potential.
6. Aside
from AMP being increased as a result of glycogen depleting exercise leading to
greater AMPK expression, the transport proteins responsible for getting leucine
into the cell are also inhibited by a low pH (which is a result of anaerobic,
glycogen depleting strength training), resulting in increased protein
breakdown. Low pH also results in reduced amino acid uptake, which suppresses
mTOR activation of protein synthesis. Beta-alanine is something that can be
taken to increase muscle carnosine levels, and act as a natural acid buffer
limiting the decrease in pH from training, as well as preventing the
attenuation of amino acid transport after a workout.
7. And
last but certainly not least, as stated earlier, muscles are primarily made up
of water (as is the entire body), therefore highlighting the importance of
adequate hydration. The more water that you can get into your muscles, the bigger
they will get. But just drinking water alone isn’t enough. You need to make
sure that you’re getting enough electrolytes like sodium and potassium, as well
as glutamine and leucine, so that your cells can “turn on” protein synthesis
and begin swelling/building up.
*If your blood
pressure and body composition are in the optimal range, then sodium and
carbohydrate consumption should only positively affect building muscle as long
as everything else is being followed accordingly.
It should go without
saying, but common sense isn’t all that common these days, so I’ll reinforce
that EVERYTHING suggested in this article is based upon BUILDING MUSCLE! If you
are trying to lean out for summer, or a physique type competition, than
dramatic changes to the suggestions above ought to be made, so don’t think that
by doing everything suggested means you will look like a bodybuilder (or
something of the sort). The fact is, bodybuilders (or any physique competitor
for that matter) go through dramatic dieting phases in which the goal is NOT to
build as much muscle as possible, because they have already done that and now
want to make sure it is visible!
Is it really that
simple?
The answer to that
is yes... and no. If you follow the guidelines presented in this article then
building muscle will happen, just as it’s supposed to, at the rate your body
will allow. If you are providing your body with the materials it needs to build
muscle (protein, carbs, vitamins, minerals, water, etc.), at precisely the most
important times (pre, peri, post workout), and are effectively activating mTOR
as much, and as frequently as possible while minimizing AMPK, and also
generating the most positive anabolic (T, GH, IGF-1, MGF) hormonal response as
possible while minimizing catabolic hormones (C), and still can’t build muscle,
then you just may be shit outta luck, because those are without a shadow of a
doubt, the most influential factors regarding muscle building. Building muscle
really is that simple (don’t confuse ‘simple’ with ‘easy’), as most things in
life are.
Everybody’s likely
heard of the “KISS” principle (Keep It Simple Stupid) at some point in their
life. As it relates to building muscle, the bridge that lies between where
you’re at now and where you ultimately want to be will be your ability to
consistently do what is needed, day in, day out, until you get there. There’s
nothing fancy about it, and there’s no real shortcuts. You have to do things
right, and you have to do them right all the time. I’ll end it with two quotes;
An excerpt of Vince
Lombardi’s speech about winning – “Winning is not a sometimes thing; it’s an
all the time thing. You don’t win once in a while; and you don’t do things
right once in a while. You do them right all the time”.
As the great
Aristotle once said – “We are what we repeatedly do. EXCELLENCE, then, is not
an act, but a habit”.
If you have any
questions about any of the theories or principles presented in this article,
feel free to contact me at ben@paramounttraining.ca. I'm available for
online consulting and personalized program design, as well as one on one
training if you are located in the Greater Toronto Area (GTA).
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