Glutamine The Essential Nonessential Amino Acid Part

by Michael Gündill

Bodybuilders know about the importance of proteins. Yet it seems that some amino acids are more important than others in the muscle-building process. Glutamine has earned a reputation as king of the anabolic aminos—but is it jus -tified? What's the big deal about glutamine, and how can you use it to your advantage?

Why Does Glutamine Stand Out?

Glutamine's importance is both quantitative and qualitative. Two-thirds of the free amino acids inside your muscles is glutamine. Muscles are not only a reservoir but also a major manufacturer. Most of the glutamine in your bloodstream is made in the muscles and organs, such as the liver. You can't get it directly from your meals, as it's digested and altered in the intestine. Many of the other amino acids, especially the branched-chain aminos (BCCAs), serve as precursors in glutamine synthesis.

Qualitatively, glutamine has a unique role in the muscle-building process. In the mid-'80s researchers discovered a very close relationship between free intramuscular glutamine levels and the protein synthesis rate. The higher the level of free glutamine inside your muscle, the faster the muscle grows. What's still unclear is whether the phenomenon is a cause or a consequence of anabolism: Is muscle growth accelerated because glutamine is high, or is glutamine upregulated to serve as raw material to support fast growth?

A popular hypothesis about the relationship between glutamine and growth is the muscle-swelling theory. Muscle anabolism can be accelerated by the swelling of the cells, which means water, ions and amino acids suddenly entering the cell, causing it to expand. The state of cellular hydration is supposed to influence its growth rate. The greater the hydration, the higher the protein synthesis rate. Cell shrinkage, on the other hand, is supposed to favor catabolism.

The relationship exists only if the swelling is not caused by cellular damage or trauma. Research has shown that the entry of glutamine into the muscle cell can increase its volume, inducing growth,1 but cellular swelling can also accelerate the entry of glutamine into the muscle—which leaves us with the debate about whether it's the cause or the consequence.

Here are two key points to remember about glutamine:

  • Glutamine makes up two-thirds of the muscle's free amino acid content.
  • You should keep muscle glutamine as high as possible because it either induces or supports growth.

Integrins: The Mechanosensitive Molecules

A mechanosensitive molecule senses how much tension is applied to muscle cells in order to modulate their growth rate. If you remain inactive, lying in bed for days, your muscle mass shrinks because of a lack of tension. As you train, the muscle contractions cause a great strain on the cellular membranes, triggering growth. It's a fascinating process, one in which integrins are believed to play an important part.

Integrins are thought to be mechanosensors. They are chains that are hooked up to both the muscle cells and the extracellular matrix; that is, the very tough structure that holds all the muscle cells together. When a muscle cell is either flexed or swollen, great pressures are applied to the integrins, as they're forced to prevent the whole structure from bursting. In addition to their structural role, however, they're also regulatory receptors. In other words, integrins transduce, or convert, train-ing-induced tension into chemical signals that re-

Glutamine makes up two-thirds of the muscle's free amino acid content, and you should keep muscle glutamine as high as possible because it either induces or supports growth.

suit in muscle growth.

It's interesting to note that whenever integrin functions are blocked, cell swelling cannot stimulate glutamine transport.2 That points up the importance of integrins' role in the growth process whenever mechanical forces—like weight training—are the main stimulator. It also links glutamine not only to growth but also to the transduction of training-in-duced tension into anabolism. So, in theory at least, glutamine may be far more important for bodybuilders than was previously thought.

Is Glutamine Truly Anabolic?

It would be too easy if researchers could agree on the mechanisms by which glutamine is linked to growth. Some claim it's both anabolic and anticatabolic, while others can detect only an anabolic or a protective influence.

Darmaun and co-workers at a research center in Florida gave glutamine intravenously to healthy adults, and the results showed that anabolism was increased with no effect on catabolism.3 Recently, he reported an experiment that's even more relevant for bodybuilders.4 He used a chemical named phenylbutyrate to deplete glutamine in the blood by 26 percent, which translated into an estimated 11 percent decrease in the protein synthesis rate. No obvious change in catabolism was detected. Please keep those two figures in mind as you read the following.

Another group of scientists managed to increase the intramuscular content of glutamine in men, which resulted in an increased muscle protein synthesis. Those findings tend to show that glutamine is a direct growth mediator—although they could also mean that the anabolic drive is restricted because a relative shortage of glutamine represents a bottleneck.

Is Glutamine Anticatabolic at All?

According to the studies mentioned above, glutamine doesn't have much impact on catabolism; however, other researchers did detect that effect. Two factors are usually suspected of causing the discrepancies. One is the way in which protein turnover is measured. The other is the methodology used, meaning the time of day, method of glutamine administration, doses, subjects, etc. An experiment by Perriello, et al., in which fasting subjects were given glutamine intravenously, showed that above all, glutamine reduced catabolism.5 The lesson for bodybuilders is that when you fast (at night, for example), the relative shortage of glutamine supply will increase muscle loss.

Here are two more points to remember:

  • Glutamine is either anabolic or else a shortage of it impairs anabolism.
  • Adequate glutamine supply may prevent catabolism.

Training-Induced Glutamine Deficit

Growing bodybuilders slowly build up their muscle glutamine stores, which can hide wide and dangerous short-term fluctuations. Each time you train, you deplete your glutamine reserves for several hours. That's a very unfortunate consequence of training, and you have to combat it.

Glutamine depletion follows a strange biphasic course. The first drop is the blood glutamine, and it occurs early in the workout. To make up for the deficit, your muscle starts manufacturing new glutamine from other amino acids, such as the BCAAs. That leads to the depletion of the other anabolic aminos. Eventually, the newly manufactured glutamine passes into the blood, which creates a shortage of muscle glutamine. If the glutamine manufacture is quick enough to compensate for the wasting of circulating glutamine, blood fluctuations may go undetected.6 If the wasting is considerably stronger than the muscle manufacture, as frequently occurs during weight training, the drop in blood glutamine will be readily apparent. Australian researcher D. Keast detected a drop of 55 percent in blood glutamine immediately after a very intense interval workout.7 He demonstrated that muscle glutamine synthesis capacities can be greatly overwhelmed during and immediately after intense training.

Even more worrisome is the fact that the effect is very long lasting. In studies conducted at the University of Birmingham, England, Walsh and co-workers were not able to detect any fall in blood glutamine immediately after exercise, probably because they used a slightly lower training intensity than Keast.6

That means the muscle manufacturing capacities were able to keep up with the blood glutamine wasting for a while. Unlike Keast, who did a single post-training analysis, however, Walsh kept repeating his glutamine measures. He discovered that blood glutamine was 16 percent below normal five hours after the workout. It would seem that glutamine wasting eventually overwhelms the manufacturing capacities, perhaps as wasting continues accelerating and/or the synthesis process is exhausted. So, if you train at 6 p.m. for two hours, at 1 a.m., while you're sleeping, all your glutamine stores will be depleted.

According to the phenylbutyrate study discussed above, a lasting shortage of glutamine causes the protein synthesis rate to be depressed for a long while after training if no specific measures are taken. Since the overnight fasting also causes glutamine depletion, the two wasting processes combine to exacerbate catabolism. Needless to say, if you retrain your muscles while glutamine stores are still low, you'll get yourself into serious trouble. Your muscle will never have a chance to recover, which will lead to chronic overtraining.

The key points to remember here are as follows:

  • Weight training depletes glutamine stores.
  • It's a very long-lasting depletion.
  • It's likely to be even more pronounced if you train at night.

Australian researcher D. Keast detected a drop of 55 percent in blood glutamine immediately after a very intense interval workout. He demonstrated that muscle glutamine synthesis capacities can be greatly overwhelmed during and immediately after intense training.

Why Is Glutamine Destroyed During a Workout?

Training enhances the body's glutamine use through four major pathways. Intense training tends to rapidly increase the output of Cortisol, which is a major waster of glutamine. That instantaneously increases the intestine's need for glutamine, which accelerates the extraction of it from the blood. Cortisol promotes the degradation of glutamine in the liver, further depleting blood glutamine.

Training increases your body's consumption of carbs, so the blood levels of both glucose and insulin are likely to decline. That causes the internal manufacture of carbs from noncarbohydrate molecules through a process called gluconeogenesis. Both the liver and kidneys attract amino acids—chiefly as alanine and glutamine—to transform them into carbohydrates.

Another major function of blood glutamine is to maintain the acid/base equilibrium. As you weight train, your muscles produce lactic acid, which passes into the blood and acidifies it. You can tell when that happens because your muscles burn at the end of an intense set.

The kidneys detect a drop in blood pH, forcing them to attract blood glutamine at an increasing pace. The renal consumption of glutamine can be enormous, which indirectly increases the bicarbonate level. Once the newly manufactured bicarbonate reaches the blood, it serves as a buffer and so binds the blood acid to render it neutral. That causes the blood pH to increase and the acid/base balance to be restored.

Another probable cause of the long-term depletion of blood glu-

Another probable cause of the long-term depletion of blood glutamine is the activation of the immune system by training. The immune tamine is the activation of the immune system by training. The immune cells use glutamine as fuel, which taxes the body reserves even further.

The Case for Glutamine Supplementation

I hope I've given you a better understand of glutamine's role in your body. A key point is that training reduces both blood and muscle glutamine. While the muscles of some bodybuilders have sufficient glutamine to cover the immediate training-induced wasting, that's not the case for many. In a matter of a few hours they run short of glutamine because of the delayed actions of training, a shortage that's likely to occur in the middle of the night, when blood glutamine tends to be depressed for other reasons. So anabolism is reduced exactly when it's supposed to be boosted.

You may think that you can escape the problem by adding a few glutamine pills during the postworkout period. It's not that easy, though, and for two reasons: 1) Most of the oral glutamine doesn't make it to the blood, and 2) even if it does, it isn't likely to enter the muscle.

Your goal, therefore, is threefold: 1) minimize the wasting of glutamine during and after training, 2) compensate for the fall in glutamine stores and 3) find out if it's possible to load your muscles with glutamine as you do with creatine in order to upregulate anabolism.

Editor's note: Michael Gilndill is a respected European researcher who specializes in physiology, endocrinology, pharmacology and nutri -tion. He has weight trained for more than 15 years.

References

1 Rennie, M.J. (1996). Responses of glutamine transport in cultured rat skeletal muscle to osmotically induced changes in cell volume. J Physiol (Lond). 492:887.

2 Taylor, P.M. (1998). The integrin-binding peptide GRGDTP prevents osmotically induced modulation of glutamine uptake in rat skeletal muscle. J Physiol (Lond). 509:195P.

3 Darmaun, D. (1996). Effect of glutamine on leucine metabolism in humans. Am J Physiol. 271:E748.

4 Darmaun, D. (1998). Phenylbutyrate-induced glutamine depletion in humans: effect on leucine metabolism. Am J Physiol. 274:E801.

5 Perriello, G. (1997). Regulation of gluconeogenesis by glutamine in normal postabsortive humans. Am J Physiol. 272:E437.

6 Walsh, N.P. (1998). The effects of high-intensity intermittent exercise on the plasma concentrations of glutamine and organic acids. Eur J Appl Physiol. 77:434.

7 Keast, D. (1995). Depression of plasma glutamine concentration after exercise stress and possible influence on the immune system. Med JAust. 162:15.

In a matter of a few hours bodybuilders run short of glutamine because of the delayed actions of training, a shortage that's likely to occur in the middle of the night, when blood glutamine tends to be depressed for other reasons. So anabolism is reduced exactly when it's supposed to be boosted.

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