Glutamine Supplements:Is it True Do they Work?

By Rudy Escobar

 

 

Introduction

     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.

The Functions of Glutamine

     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 purine and pyramidine

Serves as precursor of glutathione

Interferes with L-arginine and nitric oxide metabolism

Regulates cell size

Stimulates heat shock protein formation

Increases cytotoxicity of tumor necrosis factor-α

Activates extracellular signal-regulated kinases

Regulation of lymphocyte function

Stimulates Con-A and PHA-induced proliferation

Late activation by stimulation of the expressions of CD25, CD71, and CD45RO

Stimulates interferon-γ secretion

Stimulates lymphokine-activated killer cells

Inhibits apoptosis

Stimulates intestinal immunity (GALT)

Increases proportion of natural killer cells in the spleen

Regulation of momocyte function

Stimulates RNA synthesis

Increases interleukin secretion

Stimulates phagocytosis of opsonized Escherichia coli and ox erythrocytes

Stimulates antigen presentation

Increases expression of surface antigens

Influences differentiation

 

    

Benefits of Taking Glutamine Supplements According to Advertisements

 

     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]

 

The Faults of Glutamine

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 is 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.

 

 

Conclusion

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]

 

 

 

 

 

 

 

 

 

 

 

 

References



[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

  Back to the Stanislaus Journal of Biochemistry 2002 Table of Contents