GLUTAMINE: A CONDITIONALLY ESSENTIAL AMINO ACID WITH REMARKABLE
IMPLICATIONS FOR HEALTH AND PERFORMANCE
Bill Misner Ph.D.*
The human body replenishes its glutamine needs from pre-glutamine
amino acid substrates in the muscles and lungs. It also may be replenished
by glutamine-rich foods or supplements when the body fails to keep up with
the supply and demand process. Deficiencies in glutamine may occur as a
result of trauma, cancer, and extreme endurance exercise training. Since it
is the main fuel source for miles and miles of intestinal enterocytes,
millions of specific immune cells such as lymphocytes, macrophages, and
fibroblasts, it is scavenged from the blood stream circulating glutamine to
"feed" these cells. Glutamine is recruited for the Krebs Cycle to produce
energy [see figure 1]. How then is glutamine catabolized in the energy
cycle? Mitochondria enzymatically manufactures glutamine from other amino
acids [especially BCAA's], for transfer of energy through ATP end product
within the Krebs cycle.
GLUTAMINE DEPLETION CYCLE* [Figure 1]
GLUTAMINE
¯
GLUTAMINASE Þ NH4 [Nitrogen +]
¯
GLUTAMATE
¯
TRANSAMINASE Þ PYRUVATE + ALANINE
¯
ALPHA-KETOGLUTARATE
¯
ATP Þ KREBS CYCLE
¯
ENERGY!
* 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. [1]
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. [2] Another
researcher concludes, "Chronic overexercising depletes glutamine from
skeletal muscle causing the body to not recover completely by the next
workout." [3]
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. [4]
What applications will resolve exercise-induced glutamine deficiency?
CONCLUSION
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].
REFERENCES
[1]-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.
[2]-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.
[3]-Nick GL., Medicinal Properties in Whole Foods. Townsend Letter,
April 2002:149.
[4]-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 E-CAPS Inc.
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