Bodybuilding Nutrition-Anabolid and Anticatabolic Nutrients.pdf

160 Bodybuilding Supplement Guide

Glutamine: The Essential

Nonessential Amino Acid, Part 1

by Michael Gündill

B odybuilders know about the impor-

shrinkage, on the other hand, is supposed to favor

catabolism.

The relationship exists only if the swelling is not

caused by cellular damage or trauma. Research has

shown that the entry of glutamine into the muscle

cell can increase its volume, inducing growth, 1 but

cellular swelling can also accelerate the entry of

glutamine into the muscle—which leaves us with

the debate about whether it’s the cause or the con-

sequence.

Here are two key points to remember about glu-

tamine:

•Glutamine makes up two-thirds of the muscle’s

free amino acid content.

•You should keep muscle glutamine as high as

possible because it either induces or supports

growth.

Why Does Glutamine Stand Out?

Glutamine’s importance is both quantitative and

qualitative. Two-thirds of the free amino acids in-

side your muscles is glutamine. Muscles are not

only a reservoir but also a major manufacturer.

Most of the glutamine in your bloodstream is made

in the muscles and organs, such as the liver. You

can’t get it directly from your meals, as it’s digested

and altered in the intestine. Many of the other

amino acids, especially the branched-chain aminos

(BCCAs), serve as precursors in glutamine synthe-

sis.

Qualitatively, glutamine has a unique role in the

muscle-building process. In the mid-’80s re-

searchers discovered a very close relationship be-

tween free intramuscular glutamine levels and the

protein synthesis rate. The higher the level of free

glutamine inside your muscle, the faster the muscle

grows. What’s still unclear is whether the phe-

nomenon is a cause or a consequence of anabolism:

Is muscle growth accelerated because glutamine is

high, or is glutamine upregulated to serve as raw

material to support fast growth?

A popular hypothesis about the relationship be-

tween glutamine and growth is the muscle-swelling

theory. Muscle anabolism can be accelerated by the

swelling of the cells, which means water, ions and

amino acids suddenly entering the cell, causing it to

expand. The state of cellular hydration is supposed

to influence its growth rate. The greater the hydra-

tion, the higher the protein synthesis rate. Cell

Integrins: The Mechanosensitive

Molecules

A mechanosensitive molecule senses how much

tension is applied to muscle cells in order to modu-

late their growth rate. If you remain inactive, lying

in bed for days, your muscle mass shrinks because

of a lack of tension. As you train, the muscle con-

tractions cause a great strain on the cellular mem-

branes, triggering growth. It’s a fascinating

process, one in which integrins are believed to play

an important part.

Integrins are thought to be mechanosensors.

They are chains that are hooked up to both the

muscle cells and the extracellular matrix; that is,

the very tough structure that holds all the muscle

cells together. When a muscle cell is either flexed

or swollen, great pressures are applied to the inte-

grins, as they’re forced to prevent the whole struc-

ture from bursting. In addition to their structural

role, however, they’re also regulatory receptors. In

other words, integrins transduce, or convert, train-

ing-induced tension into chemical signals that re-

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Bodybuilding Supplement Guide 163

tance of proteins. Yet it seems that

some amino acids are more important

than others in the muscle-building

process. Glutamine has earned a repu -

tation as king of the anabolic aminos—but is it jus -

tified? What’s the big deal about glutamine, and

how can you use it to your advantage?

Glutamine

makes up

two-thirds of

the muscle’s

free amino

acid content,

and you

should keep

muscle

glutamine as

high as

possible

because it

either induces

or supports

growth.

sult in muscle growth.

It’s interesting to note that whenever integrin functions are blocked,

cell swelling cannot stimulate glutamine transport. 2 That points up the

importance of integrins’ role in the growth process whenever mechani-

cal forces—like weight training—are the main stimulator. It also links

glutamine not only to growth but also to the transduction of training-in-

duced tension into anabolism. So, in theory at least, glutamine may be

far more important for bodybuilders than was previously thought.

Training-Induced Glutamine Deficit

Growing bodybuilders slowly build up their muscle glutamine stores,

which can hide wide and dangerous short-term fluctuations. Each time

you train, you deplete your glutamine reserves for several hours. That’s

a very unfortunate consequence of training, and you have to combat it.

Glutamine depletion follows a strange biphasic course. The first drop

is the blood glutamine, and it occurs early in the workout. To make up

for the deficit, your muscle starts manufacturing new glutamine from

other amino acids, such as the BCAAs. That leads to the depletion of

the other anabolic aminos. Eventually, the newly manufactured glu-

tamine passes into the blood, which creates a shortage of muscle glu-

tamine. If the glutamine manufacture is quick enough to compensate

for the wasting of circulating glutamine, blood fluctuations may go un-

detected. 6 If the wasting is considerably stronger than the muscle manu-

facture, as frequently occurs during weight training, the drop in blood

glutamine will be readily apparent. Australian researcher D. Keast de-

tected a drop of 55 percent in blood glutamine immediately after a very

intense interval workout. 7 He demonstrated that muscle glutamine syn-

thesis capacities can be greatly overwhelmed during and immediately

after intense training.

Even more worrisome is the fact that the effect is very long lasting. In

studies conducted at the University of Birmingham, England, Walsh

and co-workers were not able to detect any fall in blood glutamine im-

mediately after exercise, probably because they used a slightly lower

training intensity than Keast. 6

That means the muscle manufacturing capacities were able to keep up

with the blood glutamine wasting for a while. Unlike Keast, who did a

single post-training analysis, however, Walsh kept repeating his glu-

tamine measures. He discovered that blood glutamine was 16 percent

below normal five hours after the workout. It would seem that glu-

tamine wasting eventually overwhelms the manufacturing capacities,

perhaps as wasting continues accelerating and/or the synthesis process

is exhausted. So, if you train at 6 p.m. for two hours, at 1 a.m., while

you’re sleeping, all your glutamine stores will be depleted.

According to the phenylbutyrate study discussed above, a lasting

shortage of glutamine causes the protein synthesis rate to be depressed

for a long while after training if no specific measures are taken. Since

the overnight fasting also causes glutamine depletion, the two wasting

processes combine to exacerbate catabolism. Needless to say, if you re-

train your muscles while glutamine stores are still low, you’ll get your -

self into serious trouble. Your muscle will never have a chance to

recover, which will lead to chronic overtraining.

The key points to remember here are as follows:

•Weight training depletes glutamine stores.

•It’s a very long-lasting depletion.

•It’s likely to be even more pronounced if you train at night.

Australian

researcher D.

Keast detected

a drop of 55

percent in

blood

glutamine

immediately

after a very

intense interval

workout. He

demonstrated

that muscle

glutamine

synthesis

capacities can

be greatly

overwhelmed

during and

immediately

after intense

training.

Is Glutamine Truly Anabolic?

It would be too easy if researchers could agree on the mechanisms by

which glutamine is linked to growth. Some claim it’s both anabolic and

anticatabolic, while others can detect only an anabolic or a protective

influence.

Darmaun and co-workers at a research center in Florida gave glu-

tamine intravenously to healthy adults, and the results showed that an-

abolism was increased with no effect on catabolism. 3 Recently, he

reported an experiment that’s even more relevant for bodybuilders. 4 He

used a chemical named phenylbutyrate to deplete glutamine in the

blood by 26 percent, which translated into an estimated 11 percent de-

crease in the protein synthesis rate. No obvious change in catabolism

was detected. Please keep those two figures in mind as you read the fol-

lowing.

Another group of scientists managed to increase the intramuscular

content of glutamine in men, which resulted in an increased muscle pro-

tein synthesis. Those findings tend to show that glutamine is a direct

growth mediator—although they could also mean that the anabolic

drive is restricted because a relative shortage of glutamine represents a

bottleneck.

Is Glutamine Anticatabolic at All?

According to the studies mentioned above, glutamine doesn’t have

much impact on catabolism; however, other researchers did detect that

effect. Two factors are usually suspected of causing the discrepancies.

One is the way in which protein turnover is measured. The other is the

methodology used, meaning the time of day, method of glutamine ad-

ministration, doses, subjects, etc. An experiment by Perriello, et al., in

which fasting subjects were given glutamine intravenously, showed that

above all, glutamine reduced catabolism. 5 The lesson for bodybuilders

is that when you fast (at night, for example), the relative shortage of

glutamine supply will increase muscle loss.

Here are two more points to remember:

•Glutamine is either anabolic or else a shortage of it impairs an-

abolism.

•Adequate glutamine supply may prevent catabolism.

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Bodybuilding Supplement Guide 165

Another

probable

cause of the

long-term

depletion of

blood

glutamine is

the activation

of the

immune

system by

training. The

immune

cells use

glutamine as

fuel, which

taxes the

body reserves

even further.

Why Is Glutamine Destroyed During a Workout?

Training enhances the body’s glutamine use through four major path-

ways. Intense training tends to rapidly increase the output of cortisol,

which is a major waster of glutamine. That instantaneously increases

the intestine’s need for glutamine, which accelerates the extraction of it

from the blood. Cortisol promotes the degradation of glutamine in the

liver, further depleting blood glutamine.

Training increases your body’s consumption of carbs, so the blood

levels of both glucose and insulin are likely to decline. That causes the

internal manufacture of carbs from noncarbohydrate molecules through

a process called gluconeogenesis. Both the liver and kidneys attract

amino acids—chiefly as alanine and glutamine—to transform them into

carbohydrates.

Another major function of blood glutamine is to maintain the

acid/base equilibrium. As you weight train, your muscles produce lactic

acid, which passes into the blood and acidifies it. You can tell when that

happens because your muscles burn at the end of an intense set.

The kidneys detect a drop in blood pH, forcing them to attract blood

glutamine at an increasing pace. The renal consumption of glutamine

can be enormous, which indirectly increases the bicarbonate level.

Once the newly manufactured bicarbonate reaches the blood, it serves

as a buffer and so binds the blood acid to render it neutral. That causes

the blood pH to increase and the acid/base balance to be restored.

Another probable cause of the long-term depletion of blood glu-

tamine is the activation of the immune system by training. The immune

cells use glutamine as fuel, which taxes the body reserves even further.

In a matter of

a few hours

bodybuilders

run short of

glutamine

because of the

delayed

actions of

training, a

shortage that’s

likely to occur

in the middle

of the night,

when blood

glutamine

tends to be

depressed for

other reasons.

So anabolism

is reduced

exactly when

it’s supposed

to be boosted.

The Case for Glutamine Supplementation

I hope I’ve given you a better understand of glutamine’s role in your

body. A key point is that training reduces both blood and muscle glu-

tamine. While the muscles of some bodybuilders have sufficient glu-

tamine to cover the immediate training-induced wasting, that’s not the

case for many. In a matter of a few hours they run short of glutamine

because of the delayed actions of training, a shortage that’s likely to

occur in the middle of the night, when blood glutamine tends to be de-

pressed for other reasons. So anabolism is reduced exactly when it’s

supposed to be boosted.

You may think that you can escape the problem by adding a few glu-

tamine pills during the postworkout period. It’s not that easy, though,

and for two reasons: 1) Most of the oral glutamine doesn’t make it to

the blood, and 2) even if it does, it isn’t likely to enter the muscle.

Your goal, therefore, is threefold: 1) minimize the wasting of glu-

tamine during and after training, 2) compensate for the fall in glutamine

stores and 3) find out if it’s possible to load your muscles with glu-

tamine as you do with creatine in order to upregulate anabolism.

Editor’s note: Michael Gündill is a respected European researcher

who specializes in physiology, endocrinology, pharmacology and nutri -

tion. He has weight trained for more than 15 years.

References

1 Rennie, M.J. (1996). Responses of glutamine transport in cultured

rat skeletal muscle to osmotically induced changes in cell volume. J

Physiol (Lond). 492:887.

2 Taylor, P.M. (1998). The integrin-binding peptide GRGDTP pre-

vents osmotically induced modulation of glutamine uptake in rat skele-

tal muscle. J Physiol (Lond). 509:195P.

3 Darmaun, D. (1996). Effect of glutamine on leucine metabolism in

humans. Am J Physiol . 271:E748.

4 Darmaun, D. (1998). Phenylbutyrate-induced glutamine depletion in

humans: effect on leucine metabolism. Am J Physiol . 274:E801.

5 Perriello, G. (1997). Regulation of gluconeogenesis by glutamine in

normal postabsortive humans. Am J Physiol . 272:E437.

6 Walsh, N.P. (1998). The effects of high-intensity intermittent exer-

cise on the plasma concentrations of glutamine and organic acids. Eur J

Appl Physiol . 77:434.

7 Keast, D. (1995). Depression of plasma glutamine concentration

after exercise stress and possible influence on the immune system. Med

J Aust . 162:15.

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Glutamine: The Essential

Nonessential Amino Acid, Part 2

by Michael Gündill

that the muscle takes up the glutamine and some sodium. Once they’re

inside the cell, the glutamine is held back while the salt is pushed out.

Even so—and despite what you may hear via the bodybuilding

grapevine—eating extra salt won’t help you with glutamine manipula-

tion unless you’re taking powerful diuretics.

The elegantly designed machinery works well unless the newly ar-

rived salt isn’t leaving the cell fast enough to match the rate of sodium

entry. If the pumps that are forcing the salt out of the cell are over-

whelmed, the ones that are pumping the extracellular salt into the mus -

cle stop working, and when they stop bringing salt into the cell, they

also stop pumping in glutamine.

There are several reasons why glutamine entry into the muscle is

blocked after a workout. For one thing, high cortisol levels will impair

it. For another, the muscle cells are already loaded with sodium. As a

general rule, whenever there’s an excess of sodium in the muscle, a

wasting process is at work.

The unwanted invasion of sodium is due to several causes. During

training muscle burn stimulates the entry of sodium in exchange for the

acid responsible for the burning sensation. After training the wear and

tear inflicted on the muscle cells precipitates the leak of blood sodium

into the muscle. Although glutamine entry is sodium dependent, sodi-

um doesn’t necessarily bring glutamine along with it when it enters the

muscle cell. In other words, sodium entry is not dependent on glu-

tamine. While sodium can freely leak into the muscle, the process by

There are

several reasons

why glutamine

entry into the

muscle is

blocked after a

workout. For

one thing, high

cortisol levels

will impair it.

T he amino acid glutamine has a unique

system to help in the glutamine manipulation.

and key role in the muscle-building

process. It’s intimately linked to

growth. The more glutamine your

muscles contain, the more they’ll

grow. Therefore, you should attempt to load your

muscles with glutamine. Unfortunately, that’s easi-

er said than done, and you face two major obsta-

cles: 1) Intense training depletes glutamine stores,

and 2) most of the glutamine you take in through

food or supplements doesn’t make it into the blood,

much less to the muscle. The question, then, is,

How do you force your muscles to accept glu-

tamine when they refuse to let it in?

What Happens to Dietary

Glutamine

Most of the glutamine you take in through food

doesn’t survive to enter your blood. It does in-

crease your blood glutamine level, 1 but between 60

and 80 percent of dietary glutamine is taken up by

the intestine and never reaches the blood. The 20 to

40 percent that’s left is handy to have, but it won’t

be enough to meet the postworkout demand.

Why Would Glutamine Enter the

Muscle Anyway?

Even if you could find a way to increase the level

of glutamine in your blood, the real goal is to load

your muscles with it. Not only would it refill the

glutamine reserves, but it would also stimulate or

support extra muscle growth. In theory, it’s possi-

ble to coax the blood glutamine into entering your

muscles, but in practice things aren’t that simple

for bodybuilders. The surface of each muscle cell

contains glutamine transporters, or pumps, which

are small holes in the cell membrane that open up

to act as a channel for glutamine. Like vacuum

cleaners they can be turned on and turned off.

In theory, when muscle glutamine levels are low,

the glutamine pumps are turned on, and when you

have an excess of muscle glutamine, they’re turned

off. Obviously, the off state is a major obstacle to

loading your muscles with glutamine. It’s a prob-

lem similar to the creatine pumps that stop working

whenever muscle creatine levels reach a critical

threshold.

Although you might wish that in the post-train-

ing period the starving muscles would easily take

up the dietary glutamine, it doesn’t work that way.

The glutamine transport from the blood to the mus-

cle is said to be sodium dependent, which means

Weightlifting Wastes Glutamine

Stores

Every time you train, you put a great strain on

your glutamine reserves, with both blood and mus-

cle glutamine becoming depleted. Muscles will re-

spond by manufacturing new glutamine from other

amino acids, especially the branched-chain amino

acids (BCAAs); however, it’s usually not sufficient

to keep up with the accelerated glutamine wasting,

and, of course, it also causes a shortage of BCAAs.

As the body cannot synthesize BCAAs, you have

to get them from food or supplements. Conversely,

since they’re glutamine precursors, taking supple-

mental BCAAs is a way to restore your body’s glu-

tamine reserves.

Training-induced glutamine wasting doesn’t stop

when your workout is over. It lasts a very long time

and keeps accelerating in the postworkout period

as your glutamine-manufacturing capacity be-

comes exhausted. It’s up to you to provide enough

glutamine or glutamine precursors to fill the gap

between the depletion and the supply. Dietary

amino acids alone won’t be strong enough to fully

ensure against a temporary glutamine shortage.

You have to recruit the power of your endocrine

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