Title: Glutamine and Athletics
Key words: Amino acids, glutamate, pathological conditions, overreaching syndrome, overtraining, immune response, post-exhaustive exercise infection
Date: July 2000
Category: 12. Sports
Author: Dr M Draper
Glutamine, the most abundant amino acid in the body, is also one of the most extensively studied, partly because of its association with the functioning of the immune system. It appears that systemic glutamine and enteral glutamate is most extensively utilised by the small intestine. The rapidly dividing enterocytes and cells of the immune system, neutrophils, lymphocytes and macrophages, appear to utilise glutamine -derived energy to maintain membrane integrity and for other cellular processes such as phagocytosis.
About 25% of total plasma glutamine is metabolised during each pass through the mucosal tissue bed1. Only a small amount of ingested glutamine reaches the systemic circulation because of the high extraction (80-95 %) by the tissues of the splanchnic bed, first detailed experimentally in pigs2 and then in humans3. It appears that most of the glutamine in the systemic circulation is derived from muscle tissue4 and if muscle mass is decreased, for instance, due to nutritional depletion (early enteral feeds did not include glutamine) then there is a reduced capacity for glutamine production. After mild to moderate exercise, such as sprinting, the blood levels increase and remain elevated for some hours after exercise. However, with longer periods of exercise, such as prolonged and/or high intensity exercise, in middle distance and marathon runners, triathletes, cyclists, swimmers, cross country skiers and rowers, the levels drop for 3 to 72 hours5.
Cellular Nutrition in the Immune System
Originally it was thought that the lymphocytes and macrophages obtained most of their energy from the oxidation of glucose. However, it has now been shown that freshly isolated lymphocytes and macrophages utilise glutamine at a rate either similiar to, or higher than, that of glucose6. This is supported by the fact that there is high maximal catalytic activity of glutaminase in these cells. This is the key enzyme in the glutamine utilisation pathway. Glutamine also provides nitrogen for the synthesis of nucleotides, purine and pyrimidines that are needed to synthetise new DNA and RNA during proliferation in lymphocytes and mRNA synthesis and DNA repair in macrophages. However, the rate of glutaminolysis in lymphocytes is very markedly in excess of the rates of synthesis of these compounds. The important point appears to be that the cells must be 'primed' with glutamine (or glucose) so they have the capacity to respond to an immune challenge or invasion by a foreign organism7.
Pathological Conditions and Glutamine levels
In man, plasma and skeletal muscle glutamine concentrations are lowered by sepsis, injury, surgery, endurance exercise and overtraining in athletes8. The lowered plasma glutamine concentrations are probably the result of increased demand for glutamine by the liver, kidney, gut and immune system exceeding the supply from diet and muscle. It has been suggested that the lowered plasma glutamine concentration contributes , at least in part, to the immunosuppression which accompanies such situations.
Animal studies have shown that inclusion of glutamine in the diet increases survival to a bacterial challenge. Glutamine or its precursors have been provided, usually by the enteral route, to patients following surgery, radiation treatment, bone marrow transplantation or after serious injury. In most cases the intention was not to stimulate the immune system but to maintain nitrogen balance, muscle mass or gut integrity. Nevertheless, the maintenance of plasma glutamine concentrations in such groups of patients, very much at risk of immune suppression, has the added benefit of maintaining immune function. Indeed the provision of glutamine to patients following bone marrow transplant resulted in a lower level of infection and a shorter stay in hospital than for patients receiving glutamine-free parental nutrition.
Overreaching and Overtraining Syndrome
Overreaching is a normal part of training which consists of hard training followed by adequate rest. This leads to super compensation and an improvement of performance9. The importance of carbohydate loading (up to 10 gms of CHO/kg bodyweight/day before intense exercise) and eating carbohydrate (high glycaemic foods 0.7-1.5 gms/kg) within 30 to 90 minutes of stopping exercise is now accepted nutritional advice to athletes10. This is to replete muscle glycogen and leads to higher blood sugar levels, an attenuated cortisol and growth hormone response and less depression of immune function5. Various studies show low muscle glycogen stores before exercise are linked to early fatigue during activity11,12. It is interesting to speculate that the ability of muscle to synthesise glutamine may be dependent on these glycogen stores and that exercise which depletes glycogen reduces or stops the synthesis of glutamine.
Overtraining Syndrome is a state of prolonged fatigue and underperformance caused by a failure to recover from hard training and competition and is most common in endurance athletes. Symptoms must have lasted at least two weeks despite adequate rest, with no other medical cause identified; athletes take weeks or months to recover in contrast to chronic fatigue syndrome (CFS) in which symptoms must have lasted at least 6 months.
The Immune Response to Exhaustive Exercise
After exhaustive exercise there is an increase in the numbers of white blood cells, especially circulating neutrophils. After a transient increase, there is a reduction in lymphocytes compared with pre-exercise levels13, 14. The adverse effects on the immune system include lower circulating T-lymphocytes, a decreased proliferative ability of lymphocytes, decreased neutrophils, decreased natural killer cells, decreased immunoglobin levels in blood and saliva, and a decreased ratio of CD4 to CD8 cells.
The Clinical Picture of the Overtraining Syndrome
Usually presenting as underperformance, the athletes describe being able to keep up with the pace of the race at the beginning but are unable to lift the pace or sprint for the line with 'nothing left in the tank'. The symptoms presented are fatigue, heavy or tender muscles and depression. Sleep disturbance is often present, along with increased anxiety, irritability, and emotional lability. Loss of appetite, competitive drive and libido are often present. Rapid resting pulse and excessive sweating on minor exertion or at night. Symptoms of minor infection especially of the upper respiratory tract (URTI) often recur each time the athlete returns to training, leading to a cycle of recurrent infection often every month9.Though there is no definitive diagnostic test (similiar to CFS) low levels of plasma glutamine beyond the normally expected period (3 - 72 hours post exercise) and remaining low for months appears to be indicative of the syndrome.
Can glutamine reduce the incidence of post exhaustive exercise infection ?A study by Castell (15) on 200 marathon runners and rowers compared the incidence of infections 7 days after these types of exhaustive exercise in two groups given either 2 drinks with 5 gms of glutamine (group G) or 5gms of malto-dextrin (placebo group P), the first drinks taken immediately afterwards and the second 1 to 2 hours later (15). The blood changes are detailed in the paper and the final outcome was a significantly higher percentage (81% , n = 72) of the glutamine group reporting no infection in the following week, compared with the placebo group (49%, n=79 , p<0.001). A similiar reduction was noticed in triathletes given branch chain aminoacids (precursors of glutamine) for one month16.Williams17 reviewing amino acid supplements comments that the benefits of glutamine on the immune system in various studies are equivocal.
ConclusionModerate exercise can improve immune function; however, excessive or exhausting exercise can leave athletes fatigued and susceptible to infection. Research into how to prevent this scenario shows that the most impressive results are obtained with carbohydrate supplementation18 Future research should, perhaps, look at combinations of carbohydrate with glutamine and micronutrients such as Vitamin C, Zinc, Chromium and perhaps Selenium (especially in the UK) to see if these complexes could improve immune function in endurance athletes.