Intense physical activity or athletic training has been known to lead to decreases in immune system function and consequently made the athlete more susceptible to illnesses such as cold and influenza (Castell, Portmans, and Newsholme 1996).
It is also known that catabolic states due to overtraining can be detrimental to an athlete's goal of muscle gain or muscle preservation and can cause a decrease in exercise performance (Boelens, Nijveldt, Houdijk, Meijer, and Van Leeuwen 2001, Hickson and Wegrzyn 1996).
Research shows that glutamine supplementation can not only help an athlete prevent illness and prevent catabolism of muscle tissue, but it can actually boost growth hormone levels, enhance glycogen storage, and hydrate muscle cells—three components important in protein synthesis or energy metabolism (Antonio and Street, 1999).
The free-form amino acid L-glutamine is becoming widely and increasingly popular among athletes such as bodybuilders and weightlifters. This product can be supplemented with in powder or capsule form and can be found at any health food or nutrition store.
Many sport supplement companies are even fortifying their protein products with additional glutamine. The marketing claims say that glutamine prevents muscle catabolism, promotes muscle anabolism, enhances the immune system, and enhances glycogen stores.
Wound healing, supporting digestive health, helping cancer patients, promoting milk production in lactating women, supporting brain wellness and mental energy, and eliminating alcohol cravings are just a few of the other promoted benefits of glutamine.
These statements imply that glutamine has important implications for athletes engaged in intensive exercise training (Antonio and Street, 1999). As with most sports supplements, you don't know what is science and what is just plain hype and a vehicle to make money. So therein lies the purpose of this research paper; to see if there is any scientific literature or research backing these claims.
Protein, like fats and carbohydrates is a macronutrient, but it is made up of building blocks called amino acids. The overall structure of a protein is determined by the order of amino acids in a chain. Proteins can be broken down into amino acids by the body (catabolic) and then reordered into new proteins (anabolic).
Glutamine is the most abundant of these amino acids in the blood and in the free amino acid pool of skeletal muscle. In fact it makes up approximately 50-60% of the free amino acids in muscle (Roth, 1990). It is stored mainly in the muscles, but can also be found in the liver, lungs, brain, and plasma of the blood. It is used as fuel by tissues such as the small intestine, immune system, and hair follicles.
Although Glutamine is classified as a nonessential amino acid because the body can synthesize it from other amino acids, most consider it to be a "conditionally essential" amino acid because of its high demand in the body at certain times. A pure L-glutamine supplement is dissolvable in a white powder form and has no taste.
Overtraining Syndrome and Immunosuppresion
During exercise or other times of physical stress such as fasting, severe injury, illness, or trauma the demand for plasma glutamine increases markedly. Intense, long duration exercise has been shown to deplete glutamine levels by as much as 34-50% and has also shown to increase the rate of infection and illness (particularly infections of the upper respiratory tract) (Roth, 1982).
It is suggested that these two results of intense sport activities go hand and hand (Castell and Newsholme 1997, Roth 1982). The reason for this, is that various cells of the immune system such as lymphocytes and macrophages depend on glutamine as a primary fuel source, and when a temporary suppression of the immune system occurs, as does with exercise, these immune system cells may call on muscle tissue to supply their glutamine.
Furthermore, demand on muscle tissue and other organs during intense exercise can be so high that the immune system may suffer from a lack of glutamine because it may require more than is supplied by our natural diet or more than we can synthesize (Miller 1999, Newsholme 1994). Consequently, it has been hypothesized that the activity of the skeletal muscles may directly influence the immune system (Keast, Arstein, Harper, Fry, and Morton 1995).
Stressors such as burns, surgery, prolonged exercise, and overtraining cause a marked decrease in glutamine concentration in skeletal muscle and plasma (Newsholme, 1994). Overtraining is a state incurred as a result of increasing training frequency, intensity, or volume while failing to balance these three variables with adequate recover periods. Overtraining syndrome is characterized by increases in cortisol levels (catabolic hormone), poor performance, fatigue, depression, nausea, etc.
Small-scale studies have shown that overtrained athletes have been found to exhibit lower plasma glutamine concentrations than non-overtrained athletes (Castell and Newsholme 1997, Keast, Arstein, Harper, Fry, and Morton 1995).
What this tells us is that because of the high demands for glutamine from the lymphocytes and macrophages during intense training and overtraining syndrome, immune system function may be compromised and contribute to the incidence of infectious disease or slower wound healing. Viral infections such as the everyday cold and flu to HIV all dramatically lower glutamine levels.
Having a glutamine deficiency will lower the levels of our protective T cells and reduce the ability of macrophages to kill viruses and bacteria (Hack, Weiss, Friedmann, Suttner, Schykowski, Erge, Benner, Bartsch, and Drodge 1997). But, not all studies show an effect of glutamine supplementation after intense exercise.
Castell, Poortmans, Leclercq, Brasseur, Duchateau, and Newsholme (1997) reported that there was no effect of glutamine ingestion of lymphocyte distribution in runners who had competed a marathon. Furthermore, glutamine supplementation provided no additional benefit in immune function to exercise-trained rats, but it did to sedentary rats (Shewchuk, Baracos, and Field 1997).
An example of the importance of glutamine in curbing infection and illness is clearly evident in a study done at Oxford University by Castell, Poortmans, and Newsholme (1996). The study compared the health status of more than 150 marathon runners up to one week following a strenuous run. Half of the test subjects were given 5 grams of glutamine after the strenuous bout of exercise, while the other half took a placebo. The end result was that the subjects that were given the glutamine were twice as likely to stay healthy for the 7 days following a strenuous marathon than the placebo group.
One further note is that glutamine also increases the production of glutathione, the most powerful antioxidant in the body. Glutathione in turn protects tissues from oxidative damage and detoxifies harmful substances such as free radicals leading to an increased immune function.
Based solely on glutamines' immune system properties, glutamine supplementation may be very important for athletes who engage in heavy, strenuous, or intense activity. It may allow them to remain healthy and consequently to train more frequently without the down periods of sickness (Greig, Rowbottom, and Keast 1995).
Enhanced Protein Synthesis and Prevention Of Muscle Atrophy
A decreased ratio of testosterone to cortisol is believed to be directly responsible for losses in muscle mass since cortisol promotes the synthesis of glutamine synthetase. By maintaining intracellular concentrations of glutamine within the skeletal muscles, the synthesis of glutamine synthetase mRNA may be inhibited and thus the loss of intracellular nitrogen through glutamine may be prevented.
Furthermore, by enhancing plasma concentrations of glutamine, the demand for free glutamine by other tissues and cells (e.g. the small intestine and immune cells) is attenuated and thus the release of glutamine from muscle tissue is reduced (Antonio and Street, 1999).
In a study done by (Hankard, Haymond, and Darmaun 1996) 7 subjects received 800 micromol/kg/hr of glutamine while 7 others received the same amount of glycine. During the infusion of glutamine, the rate of luecine appearance in the plasma remained unchanged, indicating that glutamine supplementation inhibited the breakdown of muscle protein.
In addition, the oxidation of luecine decreased and nonoxidative leucine disposal increased, indicating an increase in protein synthesis. The Glycine infusion also inhibited protein breakdown but did not result in an increase in protein synthesis.
Further evidence from Boelens, Nijveldt, Houdijk, Meijer, and Van Leeuwen (2001), and Hickson and Wegrzyn (1996), and Hickson and Czerwinski (1995) shows that glutamine is important as an anticatabolic and prevents muscle tissue atrophy (muscle wasting) and prevents downregulation of myosin heavy chain synthesis.
Studies by Haussinger, Lang, and Gerok (1994) and Vom Dahl and Haussinger (1996) suggest that glutamine supplementation may induce an anabolic effect as an osmotically active agent. These two studies indicate that changes in the cellular hydration state (and thus changes in cell volume) may act as a metabolic signal.
An increase in cell volume has been associated with cellular anabolism, while cell shrinkage has been associated with cellular catabolism. The effect of cell hydration by glutamine supplementation was enhanced when the rats in the study were starved for 24 hours (Vom Dahl et al, 1996).
Glucose Regulation and Glycogen Formation
Glutamine also plays a role in glucose regulation. Varnier and Leese (1995) explored this theory with a study done on groups of six subjects who each cycled for 90 minutes at 70 to 140% VO2 max. The exercise protocol was designed to deplete glycogen stores.
Following exercise, the subjects were infused with 30 mg/kg body weight of glutamine, alanine and glycine, or a saline solution. Two hours following exercise, muscle glycogen concentration increased significantly more in the subjects receiving glutamine than the other subjects.
Another study done by Perriello, Nurjhan, Stumvoll, Bucci, Welle, Daily, Bier, Toft, Jenssen, and Gerich (1997) took sixteen postabsorptive human subjects and infused them with glutamine, so that glutamine appeared in the plasma at a rate similar to that observed following a high protein meal.
The amount of glucose formed from glutamine within the subjects increased by seven times, independently of glucagons/insulin regulation. Rennie, Bowtell, Bruce, and Khogali (2001) also reports that intravenous or oral glutamine supplementation promoted skeletal muscle glycogen storage.
The carbon skeleton of glutamine can serve as a gluconeogenic precursor and may regulate gluconeogenesis (glucose synthesis) independently of the insulin/glucagons ratio.
Because glutamine may serve as a precursor to glucose, independently of glucagons regulation, glutamine supplementation may also enhance glycogenolysis (breakdown of glycogen to glucose in the liver) and thus increase muscle glycogen stores even when insulin levels are low (Varnier and Leese 1995, Perriello, Nurjhan, Stumvoll, Bucci, Welle, Daily, Bier, Toft, Jenssen, and Gerich 1997).
The most notable study that showed glutamine had an effect on growth hormone levels was done by Welbourne (1995) when he administered an oral glutamine load to nine healthy subjects. Two grams of glutamine was dissolved in a cola drink and ingested over a 20-min period 45 minutes after a light breakfast.
Forearm venous blood samples were obtained at zero time and at 30-minute intervals for 90 minutes. Eight of the nine subjects responded to the glutamine supplementation with an increase in plasma glutamine at 30 and 60 min before returning to the control value at 90 minutes.
90 minutes after the glutamine load both plasma bicarbonate concentration and circulating plasma growth hormone concentration were elevated. So, supplementing with a small amount of glutamine may elevate alkaline reserves as well as plasma growth hormone.
Ziegler, Benfell, Smith, Young, Brown, Ferrari-Baliviera, Lowe, and Wilmore (1990) indicate that glutamine supplementation is safe for humans short-term. However, there is little data regarding long-term usage (more than a few weeks) of glutamine supplements (Antonio and Street, 1999).
Furthermore, more research is needed which investigate the safety of glutamine supplementation at doses that would be used to promote nitrogen retention in the muscles (0.2-0.6 grams/kg bodyweight) (Ziegler, Benfell, Smith, Young, Brown, Ferrari-Baliviera, Lowe, and Wilmore 1990).
Generally speaking, the consumption of any one, single amino acid in large doses may inhibit the absorption of other amino acids since amino acids tend to compete for transport across the intestinal epithelium. Regardless, Dechelotte, Darmaun, Rongier, Hecketsweller, Rigal, and Desjeux (1991) report that glutamine is absorbed effectively in the small intestine.
Results of the cumulative data on glutamine supplementation show that glutamine may have athletic performance enhancement ability and because of this may serve as an ergogonic aid. Research on glutamine supplementation has shown to increase growth hormone levels, promote glycogen formation, promote protein synthesis, protect the immune system, and have anti-catabolic properties.
All evidence seems to indicate that glutamine can possibly favor recovery in all of these ways. But, little research has been done on resistance training athletes, with the majority of the research having been done with aerobic athletes such as marathon runners and cyclists. Further research is warranted for anaerobic training athletes such as bodybuilders, weightlifters, powerlifters, and other athletes who train in the anaerobic energy system.
Studies incorporating more subjects are also warranted. One other point is that no long term studies or high dosage studies have been done on the safety of glutamine supplementation. As we continue to learn more about the human body and how it reacts to certain compounds we will continue to see new and exciting discoveries which will pave the way for individuals, in this case athletes, to build stronger bodies and improve the quality of their training and the effects of their training.
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