© Degussa News

May 2002

Sports Nutrition:

L-Glutamine

by

Richard A. Passwater, Ph.D.

 

Exercise and competitive sports have a profound effect on muscle protein metabolism. Both increase muscle protein synthesis and muscle protein breakdown. Exercise of any type – using muscles – tears down old muscle cells to build new and stronger muscle cells.

 

The body’s net muscle protein balance (i.e., the difference between muscle protein synthesis and protein breakdown) generally remains negative in the recovery period after a round of golf in the absence of nutrient supplementation. However, it has been demonstrated that ingestion of supplements after exercise or competition stimulates muscle protein synthesis.

 

During exercise protein breakdown increases with no rise in protein synthesis. This means that training and competing can be very catabolic times, no matter what type of exercise you do. Fortunately, during the post-exercise period, this muscle catabolism can be slowed as protein synthesis begins to rise. Normally, this increase still isn’t enough to counter the protein breakdown that’s still occurring. The net result of this workout and post workout catabolism is that muscle recovery and improvement can be hampered unless proper nutrients are readily available in the bloodstream.

 

Catabolism occurs in every person regardless of lifestyle or training level. We can see this because unused muscles, such as those immobilized by casts or those in comatose patients, atrophy. Catabolism is governed by various hormonal systems as well as by mechanical stress. In other words, elevated general stress levels (such as those experienced by people who are overworked) as well as specific mechanical stress (such as that inflicted by exercise) are catabolic. That's why exercise often leads to muscle soreness - the soreness is an indication of muscle damage. Any reduction in catabolism, if the rate of anabolism remains constant, will result in an increase in the rate of muscle growth.

 

            L-Glutamine:

 

                        Glutamine is a “special” amino acid for several reasons. Glutamine is the predominant amino acid in the human body and has a central role in body metabolism as it is involved in more metabolic reactions than any other amino acid. It is so critical to the survival of the body that the body makes sure of its availability independent of diet by storing glutamine in muscles and manufacturing some quantities of glutamine from other amino acids.

 

            Dr. Douglas W. Wilmore of Harvard Medical School has summarized the major role of glutamine in sports nutrition. [Shabert & Ehrlich 1994a] Glutamine is:

 

·                    A key to the metabolism and maintenance of muscle.

·                    The primary fuel, or energy source, for the entire immune system.

·                    Essential for DNA synthesis, cell division and cell growth.

·                    Important for neutralizing toxins in the body.

 

 

 

 

Box 2. Summarizing the benefits of glutamine on muscle recovery

 

·                     Vigorous exercise depletes muscle glutamine levels.

·                     Glutamine is anti-catabolic and helps preserve muscle mass.

·                     Glutamine helps build muscles.

·                     Glutamine helps counteract lactic acid buildup that leads to fatigue and soreness.

·                     Glutamine helps protect against the effects of overtraining.

·                     Glutamine spares and replenishes muscle glycogen levels.

·                     Glutamine assists fat burning.

·                     Glutamine is critical to the immune system.

·                     Glutamine helps improve cellular antioxidant status.

 

 

 

Exercise Depletes Glutamine Levels in Muscles.

 

            Exercise causes metabolic stress in which more glutamine is consumed than the body can produce. The body attempts to maintain an adequate level of glutamine in the blood by releasing stored glutamine from the muscles. Eventually, these stores are depleted.

 

            Dr. Judy Shabert of Harvard Medical School is an expert on glutamine biochemistry. Dr. Shabert states: “Engaging in strenuous physical activity produces metabolic stress. When an individual is metabolically stressed (such as in strenuous exercise or trauma), the muscles produce significantly more glutamine in order to maintain blood (glutamine) levels. Nevertheless, concentrations of glutamine within the muscles may fall by at least 50%. [Roth et al. 1982] If enough glutamine is not taken in through food to meet the body’s demands, the muscles begin to breakdown to supply the body with glutamine.” [Shabert & Ehrlich 1994b]

 

 

            During stress, including strenuous exercise, there is a threefold increase in the release of glutamine from muscles. [Muhlbacher et al. 1984]

 

            Blood levels of glutamine remain stable at the expense of glutamine stored in muscles. [Askanazi et al. 1980] Thus, muscle glutamine stores may be deficient although blood glutamine level is near normal. However, when blood glutamine level is low, the muscle glutamine stores are definitely depleted.

 

Glutamine is Anti-Catabolic and Helps Preserve Muscle Mass

 

            The regulatory properties of a principal glutamine transport system of skeletal muscle may control the balance between muscle protein synthesis and breakdown. [Anon. 1989] Glutamine reduces the rate of muscle degradation and increases levels of plasma arginine, which can increase growth hormone release. [MacLennan et al. 1988] “we do know without a doubt that supplemental glutamine prevents muscle breakdown.” [Shabert & Ehrlich 1994d]

 

            In a seminal study, muscles undergoing breakdown (atrophy) were infused with the standard intravenous amino acid solutions used in hospitals. Muscle breakdown continued and was only minimally attenuated. When glutamine alone was infused, there was appreciably less muscle loss. When glutamine plus the standard amino acid solution were given together, muscle breakdown was essentially prevented. [Kapadia et al. 1985]

Dr. Tomas (sic) Welbourne of Louisiana State University has also demonstrated that supplemental glutamine can reduce muscle breakdown. [Welbourne & Fuseler 1993]

 

Glutamine Helps Build Muscles

 

“Glutamine availability also appears to determine the rate of protein turnover in muscle.” [Welbourne 1995]

 

            Glutamine stores in muscle cells are also highly osmotic substrates that draw water into muscle cells and hold the water. This increases muscle hardness and triggers anabolic mechanisms. [Haussinger et al. 1998] During the cell volumizing process muscle building is “turned on” and muscle breakdown is “turned off.” As glutamine moves into muscle cells it causes rapid increases in cell volume which, in turn, stimulates transport system Nm to keep increasing the rate of transport into the cell [Low et al. 1997, 1998]  The glutamine transporter system Nm found in muscle cells is unique. The transporter Nm does not “down regulate” and return the cell to “normal” as do other transport systems. The muscle cells remain in an expanded and anabolic state. Small increases in cell volume trigger potent muscle building effect. [Low et al, 1996]

 

DNA

            Glutamine has a major role in adding a nitrogen atom to make DNA, which is the template for building muscles.

 

Growth Hormone

 

            “Growth hormone helps build and strengthen muscles and clear acid from body fluids. [Hackman 1997]

 

            Athletes given glutamine in drink form had growth hormone increases of up to 430% during the following 90 minutes over that of those given a placebo. [Welbourne 1995]

 

            Muscle protein synthesis decreases after the metabolic stress of surgery. Several studies have shown that glutamine supplementation restores normal muscle synthesis. [Hammarqvist et al. 1989, 1990; Petersson et al. 1994; Barua et al. 1992]

 

Glutamine Helps Counteract Lactic Acid Buildup that Leads to Fatigue and Soreness.

 

            A limiting factor in performing exercise or other work is the buildup of lactic acid that forms. Lactic acid can cause an acid-burning of muscle cells that is experienced as next-day soreness. The more exercise performed, the more lactic acid produced. Glutamine is a major source of the nitrogen required to help regulate acid/base balance in the body.

 

The body attempts to overcome lactic acid accumulation by neutralizing the hydrogen ions of the acid with ammonia formed in the distal renal tubule cells. This ammonia is produced by de-amidation of amino acids. Thus, the more exercise, the more lactic acid and the more amino acids that have to be catabolized from muscle and the more muscle is destroyed. Glutamine contains a very labile amide group that is easier to remove than amines and amide groups of other amino acids. Thus, the principal source of urinary ammonia is normally the de-amidation of glutamine by the enzyme glutaminase. The ammonia formed within the renal tube cells react directly with hydrogen ions so that ammonium ions rather than hydrogen ions are secreted. [Harper 1969]

 

            Dr. Tomas (sic) Welbourne of Louisiana State University stated in the American Journal of Clinical Nutrition that “Physiological challenges, especially those generating an acid load (such as exercise), may confer a (dietary) essential role on glutamine under these conditions. Glutamine has an unique role in supporting renal bicarbonate production.” [Welbourne 1995] Previously Dr. Welbourne reported his study showing that supplemental glutamine can prevent acidosis. [Welbourne 1993]

 

During strenuous exercise, glutamine release from storage may not be able to counteract the build-up of lactic acid. Researchers have suggested that glutamine supplementation may enable longer, harder workouts with reduced soreness resulting. [Welbourne & Joshi 1990]

 

            Athletes given glutamine in drink form had bicarbonate increases ranging from 12 to 19 percent during the next 90 minutes compared to those given a placebo drink. [Welbourne 1995]

 

 

The increase in bicarbonate plus the buffering action of glutamine itself helps reduce lactic acid accumulation which in turn leads to fatigue and muscle soreness. [Hackman 1997]

 

Glutamine Helps Protect Against the Effects of Overtraining

 

            It has long been recognized that overtraining can result in muscle loss, colds, fever etc. and is counterproductive to athletic training. The overtraining effect is caused by lowered glutamine levels in the muscles. Physical activity directly affects the availability of glutamine to white blood cells needed to combat germs. [Walsh et al. 1998] “Many components of the immune system exhibit adverse change after prolonged, intense exertion. During this “open window” of impaired immunity (which may last for hours, days or indefinitely depending on the immune measure), viruses and bacteria may gain a foothold, increasing the risk for subclinical and clinical infection.” [Nieman 1999]

 

            “Over training in athletes is associated with depressed plasma glutamine concentration and immune system responsiveness as judged by susceptibility to infection. From this perspective, an oral glutamine supplement might prove beneficial in anticipation of such challenges.” [Welbourne 1995]

 

 

            “Glutamine is an important fuel for some key cells of the immune system. Both the plasma concentration of glutamine and the functional ability of immune cells in the blood are decreased after prolonged, exhaustive exercise. Glutamine feeding has had beneficial effects in clinical situations, and the provision of glutamine after intensive exercise has decreased the incidence of infections, particularly of upper respiratory tract infections. [Castell and Newsholme 2001] 

 

“In endurance athletes, the concentration of glutamine in blood is decreased. This decrease occurs concomitantly with relatively transient immunodepression. Provision of glutamine has been found to decrease the incidence of illness in endurance athletes. There is increasing evidence that neutrophils are a major aspect of the immune system affected by glutamine.” [Castell 2002]

 

            “Plasma glutamine responses to both prolonged and high intensity exercise are characterized by increased levels during exercise followed by significant decreases during the post-exercise recovery period, with several hours of recovery required for restoration of pre-exercise levels, depending on the intensity and duration of exercise. If recovery between exercise bouts is inadequate, the acute effects of exercise on plasma glutamine level may be cumulative, since overload training has been shown to result in low plasma glutamine levels requiring prolonged recovery. Athletes suffering from the overtraining syndrome appear to maintain low plasma glutamine levels for months or years. All these observations have important implications for organ functions in these athletes, particularly with regard to the gut and the cells of the immune system, which may be adversely affected.” [Rowbottom et al. 1996]

 

Glutamine Spares and Replenishes Muscle Glycogen Levels

 

            Glycogen stored in muscles is the primary carbohydrate fuel for intense exercise. Glutamine supplementation after exercise stimulates glycogen synthesis in muscles. Volunteers who depleted their muscle stores of glycogen by cycling to exhaustion had rapid and sustained increase of muscle and blood glycogen with glutamine infusion, but not with alanine, glycine or saline infusion. Glutamine promotes muscle glycogen accumulation by mechanisms possibly including diversion of glutamine carbon to glycogen. [Varnie et al. 1995; Hargreaves & Snow 2001; Rennie et al. 2001]

 

Glutamine is just as effective as high-dose carbohydrate supplementation. This is of interest to athletes who desire to restrict their carbohydrate intake. A study has shown that 8 grams of glutamine was as effective in restoring muscle glycogen levels as 61 grams of glucose. The combination was more effective than either alone. [Bowtell 1999]

 

 

Glutamine and Body Composition (Reduced body fat and increased muscle)

 

 

Glutamine supplementation of a high-fat diet reduces body-weight and attenuates hyperglycemia and hyperinsulinemia. [Opara et al. 1996] Subjects taking a glutamine supplement had accelerated fat burning compared to those taking a placebo. Exercise was involved in this study and the increased fat burning is thought to be a factor of the glutamine supplementation. [Welbourne & Joshi 1990, Welbourne 1995]

Glutamine is Critical to the Immune System and Helps Protect Against Infections Ranging From the Common Cold to Bacterial Infections and Inflammation

 

Highly trained athletes develop more than normal amounts of infections due to overtraining. “A little exercise enhances the immune system, but too much decreases blood glutamine levels, promotes fatigue and prevents the immune system from responding appropriately to an infectious insult.” [Shabert and Ehrlich 1994e]

 

Glutamine is essential for immune cells to grow and function. [Eagle 1955, Eagle et al., 1956] Glutamine is critical for the functioning of the antibody immunoglobulin A, leukocytes (white blood cells), neutrophils and other components including various cytokines. [Baskerville et al. 1986] HIV-positive patients have low glutamine stores. This glutamine deficiency is a cause of the lean body mass wasting in AIDS. [Shabert & Wilmore 1996]

 

Reduced glutamine levels lead to impaired immune function because of a reduced capacity of immune cells to proliferate. [Newsholme et al. 1987] Low plasma levels of glutamine mean a decreased availability of glutamine for macrophages and lymphocytes [Boelens et al. 2001]

 

Dr. Tomas (sic) C. Welbourne of the Department of Physiology at Louisiana State University College of Medicine concluded in the American Journal of Clinical Nutrition in 1995 that “Given the fundamental roles played by glutamine in supporting cellular and organ function, it is not surprising to find multiorgan-dependent processes such as the immune and anti-inflammatory response to be dependent, in part, on glutamine.” [Welbourne 1995]

 

“Glutamine is essential during certain inflammatory conditions, such as infection and injury. During inflammatory states, glutamine consumption may outstrip endogenous production and a relative glutamine deficiency state may exist. The overall benefit of providing an appropriate glutamine-supplemented diet to all metabolically compromised patients arises from the multiple anabolic and host-protective effects of this amino acid, of which immunomodulation is only one important facet of glutamine’s essential nature.” [Wilmore & Shabert 1998]

 

 

Glutamine Helps Improve Cellular Antioxidant Status.

 

            Glutamine enhances the body’s production of glutathione. Glutamine is an indirect precursor for glutathione, a major antioxidant within cells. Glutamine is converted to glutamate for the purpose of synthesizing glutathione. Glutamine sustains ATP, phosphocreatine and glutathione. [Rennie et al. 2001]

 

 

 

Important Difference Between Glutamine and Glutamate.

 

            Glutamine is not to be confused with the amino acid glutamate. Glutamate, rather than glutamine, is normally provided in protein supplements for athletes. Glutamine contains the amide group that gives glutamine its special properties.


 

 

 

References

 

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Barua, J. M., et al., “The Effect of Glutamine Supplementation on Muscle Protein Synthesis in Post Surgical Patients Receiving Glutamine-Free Amino Acids Intravenously.” Proc. Nutr. Soc. 51: 104A (1992).

 

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© 2002 Degussa News and Richard A. Passwater, Ph.D.

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