By William Misner, Ph.D.
William Misner, Ph.D.
From 1996 until his retirement in 2006, Dr. Bill worked full-time as Director of Research & Development at Hammer Nutrition. Among his many accomplishments, both academically and athletically, he is an AAMA Board Certified Alternative Medicine Practitioner and the author of "What Should I Eat? A Food-Endowed Prescription For Well Being".
GLUTAMINE DEPLETION CYCLE* [Figure 1]
GLUTAMINASE NH4 [Nitrogen +]
TRANSAMINASE PYRUVATE + ALANINE
ATP KREBS CYCLE
* KEY: Enzymes colored in green.
Glutamine is the most abundant free amino acid in human muscle and plasma and is utilized at high rates by rapidly dividing cells, including leucocytes, to provide energy and optimal conditions for nucleotide biosynthesis. As such, it is considered to be essential for proper immune function. During various catabolic states including surgical trauma, infection, starvation and prolonged exercise, glutamine homeostasis is placed under stress. Heavy exercise from overtraining or over-reaching depletes both circulating and muscle stores of glutamine. Glutamine is also the most abundant free amino acid in muscles, generating over 50% of the muscle-bound free amino acids, with alanine a distant 2nd in providing 10% of the free muscle aminos. During and following exercise 60% of the aminos cannibalized during exercise are from glutamine and alanine muscle stores. Generally, the Branched Chain Amino Acids[BCAA] are then selectively induced to replete losses of glutamine and alanine. This is why a number of energy products[such as Hammer Gel], formulate the ingredient BCAA's[Leucine, Valine, Isoleucine] for replacing glutamine and alanine expenditures due to their loss in exercise and their dietary exogenous absence. High protein sources of Glutamine are Hammer Whey Pro[1000 milligrams glutamine/serving], fish, legumes, raw cabbage, raw beets, and other meats. One of the problems with getting enough glutamine is that heating tends to destroy it. Repletion then may depend on our body's capacity to replenish it from other amino acids or exogenous donation in supplemental form. Glutamine is the most abundant amino acid in the bloodstream; at levels as high as 35% amino acid nitrogen. The bloodstream's circulating glutamine is tapped when intestinal enterocytes do not have enough glutamine as their primary source of energy. When the intestinal epithelial cell requirements for glutamine are lacking, muscle glutamine depletion is an indirect result as observed in hospital settings when critically ill patients suffer from muscle-waisting syndrome [Cachexia]. The same syndrome may occur in ENDURANCE ATHLETES WHO OVERTRAIN. When plasma and/or intestinal glutamine levels fail or "get behind", bacteria, fungus and other toxins may translocate across intestinal membranes causing the body to be predisposed to react allergically or to contract gastric stress, irritable bowel, and cold or flu-like illness. With overtraining, immune system failure is accurately measured proportionately to the athlete's circulating glutamine levels.
Falls in the plasma glutamine level (normal range is 500 to 750 mumol/L after an overnight fast) are observed following endurance events and prolonged exercise. These levels remain unchanged or temporarily elevated after short term, high intensity exercise. Plasma glutamine has also been reported to fall in patients with untreated diabetes mellitus, in diet-induced metabolic acidosis and in the recovery period following high intensity intermittent exercise. Common factors among all these stress states are rises in the plasma concentrations of cortisol and glucagon and an increased tissue requirement for glutamine for gluconeogenesis. It is suggested that increased gluconeogenesis and associated increases in hepatic, gut and renal glutamine uptake account for the depletion of plasma glutamine in catabolic stress states, including prolonged exercise. The short term effects of exercise on the plasma glutamine level may be CUMULATIVE, since heavy training has been shown to result in low plasma glutamine levels (< 500 mumol/L) requiring long periods of recovery. Furthermore, athletes experiencing discomfort from the overtraining syndrome exhibit lower resting levels of plasma glutamine than active healthy athletes. Therefore, physical activity directly affects the availability of glutamine to the leucocytes and thus may influence immune function. The utility of plasma glutamine level as a marker of overtraining has recently been highlighted, but a consensus has not yet been reached concerning the best method of determining the level. Since injury, infection, nutritional status and acute exercise can all influence plasma glutamine level, these factors must be controlled and/or taken into consideration if plasma glutamine is to prove a useful marker of impending overtraining. 
Indications of glutamine depletion incidence appear as a higher rate of infections and allergies in subjects whose endurance training is extreme. Researchers compared the effects of exercise at 80% VO2max resulting in fatigue within 1 hour with more prolonged exercise at a lower work rate of 55% VO2max for up to 3 hours on blood neutrophil function and plasma concentrations of cortisol, glutamine and glucose. Eighteen healthy male subjects (19-26 years, VO2max 54-66 ml x kg(-1) x min(-1)) cycled on an electrically braked ergometer at 80% VO2max to fatigue from 18-56 minutes. On another occasion, separated by at least one week, subjects performed exercise on the same ergometer at 55% VO2max for 3 hours or to fatigue, whichever came first. Mean exercise time range to fatigue was 141-187 minutes. Both exercise bouts caused significant elevations of the blood leukocyte count and plasma cortisol concentration and reductions in the in vitro neutrophil degranulation response to bacterial lipopolysaccharide and oxidative burst activity. After exercise at the lower work rate for a longer duration, plasma cortisol concentration was higher, blood leucocyte and neutrophil counts were higher, blood lymphocytes, plasma glucose and indices of neutrophil function were lower than those observed at 80% VO2max. PLASMA GLUTAMINE ONLY FELL SIGNIFICANTLY DURING RECOVERY AFTER THE MORE PROLONGED EXERCISE. These researchers concluded that when exercise is very prolonged, the diminution of innate immune function is greater, or at least as great as that observed after fatiguing exercise at higher work rates. Furthermore, reductions in neutrophil function after exercise at 80% VO2max WERE NOT RELATED to changes in the plasma glutamine concentration, although both plasma glutamine and neutrophil function were decreased at 1 hours and 2.5 hours post-exercise in the long duration exercise trial.  Another researcher concludes, "Chronic overexercising depletes glutamine from skeletal muscle causing the body to not recover completely by the next workout." 
Immunosuppression by athletes involved in heavy training has numerous origins. Training and competitive surroundings may increase the athlete's exposure to pathogens and provide optimal conditions for pathogen transmission. Heavy prolonged exertion is associated with numerous hormonal and biochemical changes, many of which potentially have detrimental effects on immune function. Furthermore, IMPROPER NUTRITION can compound the negative influence of heavy exertion on immunocompetence. An athlete exercising in carbohydrate-depleted state experiences larger increases in circulating stress hormones and a greater perturbation of several immune function indices. The poor nutritional status of some athletes may predispose them to immunosuppression. For example, dietary deficiencies of protein and specific micronutrients have long been associated with IMMUNE DYSFUNCTION. Although it is impossible to counter the effects of all of the factors that contribute to exercise-induced immunosuppression, it has been shown to be possible to minimize the effects of many factors. Athletes can help themselves by EATING A WELL-BALANCED DIET that includes ADEQUATE PROTEIN AND CARBOHYDRATE, sufficient to meet their energy requirements. This will ensure a more than adequate intake of trace elements without the need for special supplements. CONSUMING CARBOHYDRATES (but not glutamine or other amino acids) DURING EXERCISE attenuates rises in stress hormones, such as cortisol, and appears to limit the degree of exercise-induced immunosuppression, at least for non-fatiguing bouts of exercise. 
What applications will resolve exercise-induced glutamine deficiency?
Endurance athletes are predisposed to immune compromise by depressed gastric functions from prolonged aerobic exercise more than short-term sessions. A preventive resolution of this disorder suggests increasing specific glutamine-rich supplements or following dietary-exercise protocols:
A-Glutamine-enhanced whey protein concentrates may be taken post-exercise. [1.5 scoops Hammer Whey Pro per 100 lbs. body weight]
B-Fish, raw legumes, raw cabbage, raw cabbage juice may be ingested post-exercise.
C-Free-form Glutamine should be consumed post-exercise or 3 hours prior. [2000 mg]
D-Carbohydrates should be taken during exercises. [240-280 calories/hour]
E-Short-term "easy" aerobic exercise need to be alternated prior to and following prolonged exercise.
F-Periodic rest days should be imposed post-workout of over 1 hour or if morning resting heart rate exceeds 5 beats per minute above base rate.
G-Do not take Glutamine during exercise due to the initial increase in NH4- [Nitrogen release during glutamine metabolism].
-Walsh NP, Blannin AK, Robson PJ, Gleeson M., Glutamine, exercise and immune function. Links and possible mechanisms. Sports Med. 1998 Sep;26(3):177-91. Review.
-Robson PJ, Blannin AK, Walsh NP, Castell LM, Gleeson M., Effects of exercise intensity, duration and recovery on in vitro neutrophil function in male athletes. Int J Sports Med. 1999 Feb; 20(2): 128-35.
-Nick GL., Medicinal Properties in Whole Foods. Townsend Letter, April 2002:149.
-Gleeson M, Bishop NC. Special feature for the Olympics: effects of exercise on the immune system: modification of immune responses to exercise by carbohydrate, glutamine and anti-oxidant supplements., Immunol Cell Biol. 2000 Oct;78(5):554-61. Review.
*Bill Misner Ph.D is the Director of Research & Product Development for Hammer Nutrition Inc.