As
human beings, we tend to want to be physically fit, and
look good in any clothes we wear. However, having a good body,
and staying fit is not an easy task. Every year, supplements are out on the
market, offering people ways possibilities in which they canto increase
muscle mass, and be more energyetic.
For a bodybuilder or anyone that is serious about their workout, more energy
and muscle mass is the main goal.
In recent years, glutamine supplements have
been the most sold on the marketvery popular.
According to advertisements of these supplements, glutamine can increase anabolic hormone
levels, such as
testosterone by 430%, prevent muscle breakdown, improve immune system,
increase protein synthesis, and improve intestinal health.
The object of this study is to review the how glutamine pathway
works
in muscles, the benefits of glutamine in the body, and studies of
glutamine intake. By doing this review, the intentions are to understand and to evaluate
if
what it is said onregarding the advertisements about glutamine
supplementation is true or not.
Glutamine
(Gln) is defined as a nonessential amino acid. Skeletal muscles are the primary
sites for the synthesis and storage of Glutamineglutamine. GGlutamine
contributes
composes
to about sixty percent of the free
amino acids, within the skeletal muscle. Glutamine
It is
also known to be a fuel for enterocytes, cells located in the intestine, and some
cells of the immune system.[1]
Glutamine is also the most abundant amino
acid within the plasma. Glucocorticoid hormones, such as cortisol, are released
during times of stress in the muscle. These hormones promote and
promote the proteolysis of muscle proteins and the release of
glutamine into the plasma to satisfy the increased demand for free glutamine.
Glutamine is required for the synthesis of
nucleotides. This is important for the division of cells such as enterocytes
and the immune cells. For the immune system, cells such as the lymphocytes and
macrophages depend on glutamine as their primary fuel source. [2]
The dDecreases in
plasma and the muscle glutamine pool have been found in life-threatening
conditions associated with muscle wasting, such as in sepsis, cancer cachexia,
burn injury, and trauma.[3]
Glutamine is metabolized via glutamate and α-ketoglutarate, which enters
The Citric Acid (TCA)Cycle. The excess nitrogen from glutamine is either
released as ammonia or transaminated onto a carbon skeleton, thusas a result
producing alanine or asparagine.[4] (see figure 1)
Figure 1: Ammonia converted to
Urea18

Glutamine
is involved in different regulations in our body. There are mainly
three, which are the regulation
of cell functions, regulation
of lymphocyte function, and and regulation
of momocyte function.which
are shown in the following The following table obtained from a study6
done on Glutamine,
lists some examples of these regulative functions.
Table 1:
Regulative Potency of Glutamine
Regulation of cell functions
Serves as
precursor of glutathione
Regulates cell
size Stimulates heat
shock protein formation
Regulation of lymphocyte function
Stimulates
lymphokine-activated killer cells Inhibits apoptosis
Regulation
of momocyte function
Stimulates
RNA synthesis
Stimulates antigen
presentation Increases
expression of surface antigens Influences
differentiation |
Glutamine supplements are advertised as being able to increasing
increase
hormone levels, decrease the risk of over training, increase protein
synthesis, and improve the immune system. According to these advertisements,
glutamine indirectly promotes growth by increasing the hydration state of
muscle cells. By swelling the cells with water, the breakdown of protein,
glycogen, and glucose is inhibited. By avoiding the dehydration of the cell, the
shrinking of the cellcell shrinkage is avoided.,
which
if it
happens could cause aShrunken cells go into a catabolic state, or and the result is the
breakdown of protein in the muscle.[5]
It has been mentioned by these
advertisements that glutamine works by sparing saving the
muscle tissue from being catabolized in order to provide glutamine for other
cells in the body. This then, allows
the muscle tissue to use gGlutamine
to synthesize new protein tissue. It has also been mentioned by
them that enough insulin and glutamine together
seem to work better at volumizingtogether to increase
the volume of the cell.
Is Glutamine as good as it is advertised?
In 1959, H. Eagle
reported that gGlutamine
is essential for growth of mammalian cells in culture media. In his experiment,
growth of cells was achieved at concentrations of 2mM/L.[6]
Glutamine is important as a
constituent of proteins, and as a central metabolite for amino acid
transamination via α-ketoglutarate and glutamic acid.
Recent studies have found that glutamine is
released mainly from skeletal muscle and delivered to the intestine, blood
cells, liver, and kidneys.[7]
Under starvation and catabolic states, glutamine delivers nitrogen from the
skeletal muscles to all other glutamine dependent organs.6 This also
means that when an athlete is exercising hard, his need of synthesis of
glutamine is important for theincreased due to the
needs of supply to the other organs. However,
because of the hard training, glutamine sometimes is not synthesized fast
enough.
Glutamine via glutamate,
cysteine, andor glycine is
the precursor amino acid for the synthesis of glutathione. Glutathione is present in the cell, in reduced and oxidized forms.
The ratio of the reduced to oxidized form of gGlutathione
is the most important regulator of the cell’s redox potential. A decrease in Gglutathione is
important because its decrease is associated with physical
exercise, aging, and Hepatitis C infection. 6 It was foundA that the preservation
of hepatic Glutathione levels could be preserved by Glutamine
administration was found in studies ofin rats that had
acetaminophen toxicity.[8]
As mentioned previously, the rate of release
of Glutamine from skeletal muscle increases in starvation, acidosis, trauma,
and muscle stress. This indicates that there is an increase of demand for
glutamine, which ends up
being an excess of to theexceeding the
person’s
capability to synthesize glutamine. However, recommendations of glutamine
supplementation are is said to promote protein synthesis and
inhibit protein catabolism in muscle.[9], wThis
supplementation can aid to satisfy thehich can satisfy the demand of glutamine.
In a study done in rats[10],
a diet with supplemented glutamine was given to the rats. When the rats were
examined, they exhibited high plasma glutamine concentrations.,
whereas
rRats
that were fed a carbohydrate and protein diet showed the lowest plasma glutamine
concentrations. Muscle and liver glutamine concentrations were also higher in
the rats that were feed glutamine-supplemented diets. This
study concluded that by supplementing glutamine to the rats
in situation of catabolic stress was beneficial.
Plasma and mMuscle gGlutamine
concentrations are often decreased in critical illnesses. In a recent study[11],
made
in athletes undergoing intensive, and
prolonged
training. These athletes suffered
an increased risk of infection; this was, due to an apparent immunosuppresion.
In particular, upper respiratory infections that is
common in intensive prolonged training than in sedentary people that would
generally benefit from, which areare more common in people who have intensive prolonged
training, than
in sedentary people. that would generally benefit from, moderate regular
exercise. The study was evaluatedconducted on a group of two
hundred athletes. These athletes were divided in four different groups, which
were marathon, ultra-marathon, mid-distance runners, and rowers. InAfter commando-style training of the ultra-marathon runners, and the rowers, after commando-style
training, their plasma glutamine
levels were lower than the glutamine levels of in the marathon, and mid-distance runners. All of the athletes were also
evaluated for infections for a period of seven days. As expected the
athletes with the lower
plasma glutamine levels (20 %),
had more infections than the athletes with higher levels of plasma glutamine. (12-15 %). In
this study, in another
group of athletes, divided in two groups, were either given glutamine
supplements to one group, andor placebo. to the other group. The result was
that tThe group that had the glutamine supplements (about 80%) reported fewer infections than the group with
placebo (about 48%)). . According
to this study, gGlutamine
ssupplementation
appeared to decrease the number of infections after prolonged exercise and
intensive training. This means that gGlutamine
helps to improve the immune system.
Besides increasing the rate of muscle
protein synthesis in surgical patients, a Gglutamine-enriched
total parenteral nutrition,
has decreased the number of infections in bone marrow transplant patients.[12]
Glutamine
feeding in cColorectal cancer patients after surgery,surgery may also
considerably improve after a gGlutamine-enriched
parenteral
nutrition.[13]
Glutamine supplementation should have a
significant influence on the metabolism of branched-chain amino
acids (BCAAs))
metabolism..3
To confirm this,
situation
a study was done on intact and endotoxemic rats (rats treated with
tumor necrosis factor-a). The infusion of gGlutamine
and aAlanine
decreased the plasma BCAAs levels, and improved protein balance
associated with a higher decrease in whole-body
proteolysis than in protein synthesis.[14]
There
is not much evidence known about the side effects due
to problems involving glutamine
supplementation
intake. However, gGlutamine
has a great regulative potency, which in some cases can interfere with some
normal processes if it i’s
present in excess. One of the processes of concern is apoptosis. Glutamine
inhibits apoptosis.6,
which
as we knowProgrammed, cell death is important in
some aspects, for the development of other functionsfor example, the development of the embryos, and the control of
cells with DNA damage., or the development of finger bones.
In a study[15],
was found that fFeeding excess Glutamine lead to high
ammonium production in batch, fed-batch, and chemostat cultures (types of cell lines
and culture medium), which reduces cell number, visibility, and
productivity.[16]
The decrease in
the cell number contradicted on what advertisements had mentioned
previously about glutamine increasing cell volume. It was found that Anabolic
reactions involving Glutamine are situated in the cytosol, while glutamine
catabolism is situated in the mitochondria..4
Excess glutamine can
also be a risk to the body, because it can introduce excessive ammonia in the
body. In
theory two moles of ammonium can be produced per mole of glutamine consumed.4 Also, the consumption of any
single amino acid in large doses can inhibit the absorption of other amino
acids, since amino acids tend to compete for transport across the intestinal
epithelium.
As it has been
studied, Glutamine has many functions in the body. The intention
of this study was to find out if gGlutamine
supplements would have the effect in the
body as they have been advertised. As it was reviewed, gGGlutamine
has shown to aid in the increases of muscle
size by preventing the catabolism of proteins. It was also shown that
gGGlutamine
supplementation apparently would decreases infections in athletes,athletes; which
meant thatthus,. Gglutamine can helps to improve
the immune system.
We can now conclude
that gGlutamine
supplements can may work as they are advertised, because they
follow the natural glutamine pathwayas the studies previously mentioned, it can
increase cell volume, and improve the immune system. However, although gGlutamine
supplements have been proven to work, it is important to take in account the
dosage that it is going to be used, to avoid the
production of excessive ammonia in the body.. As previously
mentioned, Since we have learned that eexcess glutamine
can leads
to high ammoniaum
production.,
itIt is necessary
to keep the dosage low enough to avoid excess ammonium in the body. In theory two moles of ammonium can be produced per
mole of glutamine consumed.4 Another
reason to control the concentration of glutamine is because ofdue to
competition of amino acids. As previously mentioned Tthe consumption
of any single amino acid in large doses has the chance tocan inhibit the
absorption of other amino acids, since amino acids tend to compete for the
transport across the intestinal epithelium. However, the concentration of gGlutamine
supplement cannot be too low, because the muscle tissue needs enough to prevent
protein breakdown. In other words, the amount of Glutamine needed depends on
the intensity of the exercise that the muscle receives.
In
general Glutamine supplements are good for athletes that want to increase
muscle size, and energy. The recommended dosage can be of about 15-35 grams,
which can preserve muscle glutamine, provide fuel for cells with rapid
turnover, and improve overall nitrogen balance.[17]
[1] Newsholome Eric, DSC and Gil Hardy. Supplementation of Diets with Nutritional Pharmaceuticals.
Nutrition Vol. 13, No. 9, 1997.
[2] Glutamine description. www.geocities.com/Hotsprings/Spa/9971/glutamine.html. Read on 2/28/02.
[3] Holeček, Milan, MD. Relation Between Glutamine, Branched-Chain Amino Acid, and Protein
Metabolism. Nutrition 18:130-133, 2000.
[4] Vriezen Nienke, Bastian Romein, Karol Ch, A.M. Luyben. Effects of Glutamine Supply on Growth and
Metabolism of Mammalian Cells in Chemostat Culture. Biotechnology Bioengeneering
54: 272-286, 1997.
[5] “Glutamine” Protect Muscle Catabolism – Get Leaner, Fuller, Harder, and Increase Protein Synthesis.
http://www.afordablesupplements.com/glutamine_article.asp. Read on 2/16/02.
[6] Roth, Erich, Rudolf Oehler, Nicole Manhart, Ruth Exner, Barbara Wessner, Eva Strasser, and Andreas
Spittler. Regulative Potential of Glutamine – Relation to Glutathione Metabolism.
Nutrition 18:217-221, 2002.
[7] Abumrad NN, Williams P, Fexes-Steed, et al. Inter-organ Metabolism of Amino Acids in Vivo.
Diabetes Metabolism Rev 1989; 5:213.
[8] Hong RW, Rounds JD, Helton WS. GlutaminePreserves Liver Glutathione after Lethal Hepatic Injury.
Annual Surgery 1992; 215:114.
[9] Jepson MM, Bates PC, Broadbent P, Pell JM, Millward DJ. Relationship between Glutamine
Concentration and Protein Synthesis in Rat Skeletal Muscle. American Journal of Physiology 1998:255:E166.
[10] Boza, Julio J, Marco Turini, Denis Moënnoz, Frank Montigon, Jacques Vuichoud, Nathalie Gueissaz,
Gerard Gernaud, Etienne Pouteau, Christelle Piguet-Welsch, Paul André Pinot, and Oliver Ballèvre. Effect of Glutamine Supplementation on Tissue Proteins Synthesis Rate of Glucocorticoid-Treated Rats. Nutrition 17:35-40, 2000.
[11] Castell, LM, Poortmands SR, Newsholome EA. Does Glutamine Have a Role in Reducing Infections in
Athletes. European Journal of Appl Physiology 1996;73:488.
[12] Ziegler TR, Young LS, Benfell K. Clinical and Metabolic Efficiancy of Glutamine Supplemented
Parenteral Nutrition After Bone Marrow Transplant. Ann Intern Med 1992;116:821.
[13] Newsholome, Eric, and Gil Hardy. Supplementation of Diets with Nutritional Pharmaceuticals.
Nutrition 13;837-839, 1997.
[14] Holeček, Milan, Skopec, F, Skalska, H, Sprongl L. Effect of Alanyl-Glutamine on Leucine and Protein
Metabolism in Endotoxemic Rats. JPEN 2000;24:215.
[15] Butler, M, Spier, RE. The Effects of Glutamine Utilization and Ammonia Production on The Growth of
BHK cells in Microcarrier Culture. Journal of Biotechnology 1:187-196, 1984.
[16] Butler, M, Spier, RE. The Effects of Glutamine Utilization and Ammonia Production on The Growth of
BHK cells in Microcarrier Culture. Journal of Biotechnology 1:187-196, 1984.
[17] Furst, P. Evidence for a Nutritional need for Glutamine in Catabolic Patients. Kidney Int 36:5287-92,
1989.
18 Nelson, David L.
Michael M. Cox. Lehninger Principles of
Biochemistry. New York 2000. Worth
Publishers. p. 625.
Copyright © 2002 Rudy Escobar and Koni Stone
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