Glutamine The Essential Nonessential Amino Acid Part

by Michael Gündill

The amino acid glutamine has a unique and key role in the muscle-building process. It's intimately linked to growth. The more glutamine your muscles contain, the more they'll grow. Therefore, you should attempt to load your muscles with glutamine. Unfortunately, that's easier said than done, and you face two major obstacles: 1) Intense training depletes glutamine stores, and 2) most of the glutamine you take in through food or supplements doesn't make it into the blood, much less to the muscle. The question, then, is, How do you force your muscles to accept glutamine when they refuse to let it in?

Weightlifting Wastes Glutamine Stores

Every time you train, you put a great strain on your glutamine reserves, with both blood and muscle glutamine becoming depleted. Muscles will respond by manufacturing new glutamine from other amino acids, especially the branched-chain amino acids (BCAAs); however, it's usually not sufficient to keep up with the accelerated glutamine wasting, and, of course, it also causes a shortage of BCAAs. As the body cannot synthesize BCAAs, you have to get them from food or supplements. Conversely, since they're glutamine precursors, taking supplemental BCAAs is a way to restore your body's glutamine reserves.

Training-induced glutamine wasting doesn't stop when your workout is over. It lasts a very long time and keeps accelerating in the postworkout period as your glutamine-manufacturing capacity becomes exhausted. It's up to you to provide enough glutamine or glutamine precursors to fill the gap between the depletion and the supply. Dietary amino acids alone won't be strong enough to fully ensure against a temporary glutamine shortage. You have to recruit the power of your endocrine system to help in the glutamine manipulation.

What Happens to Dietary Glutamine

Most of the glutamine you take in through food doesn't survive to enter your blood. It does increase your blood glutamine level,1 but between 60 and 80 percent of dietary glutamine is taken up by the intestine and never reaches the blood. The 20 to 40 percent that's left is handy to have, but it won't be enough to meet the postworkout demand.

Why Would Glutamine Enter the Muscle Anyway?

Even if you could find a way to increase the level of glutamine in your blood, the real goal is to load your muscles with it. Not only would it refill the glutamine reserves, but it would also stimulate or support extra muscle growth. In theory, it's possible to coax the blood glutamine into entering your muscles, but in practice things aren't that simple for bodybuilders. The surface of each muscle cell contains glutamine transporters, or pumps, which are small holes in the cell membrane that open up to act as a channel for glutamine. Like vacuum cleaners they can be turned on and turned off.

In theory, when muscle glutamine levels are low, the glutamine pumps are turned on, and when you have an excess of muscle glutamine, they're turned off. Obviously, the off state is a major obstacle to loading your muscles with glutamine. It's a problem similar to the creatine pumps that stop working whenever muscle creatine levels reach a critical threshold.

Although you might wish that in the post-train-ing period the starving muscles would easily take up the dietary glutamine, it doesn't work that way. The glutamine transport from the blood to the muscle is said to be sodium dependent, which means

that the muscle takes up the glutamine and some sodium. Once they're inside the cell, the glutamine is held back while the salt is pushed out. Even so—and despite what you may hear via the bodybuilding grapevine—eating extra salt won't help you with glutamine manipulation unless you're taking powerful diuretics.

The elegantly designed machinery works well unless the newly arrived salt isn't leaving the cell fast enough to match the rate of sodium entry. If the pumps that are forcing the salt out of the cell are overwhelmed, the ones that are pumping the extracellular salt into the mus -cle stop working, and when they stop bringing salt into the cell, they also stop pumping in glutamine.

There are several reasons why glutamine entry into the muscle is blocked after a workout. For one thing, high Cortisol levels will impair it. For another, the muscle cells are already loaded with sodium. As a general rule, whenever there's an excess of sodium in the muscle, a wasting process is at work.

The unwanted invasion of sodium is due to several causes. During training muscle burn stimulates the entry of sodium in exchange for the acid responsible for the burning sensation. After training the wear and tear inflicted on the muscle cells precipitates the leak of blood sodium into the muscle. Although glutamine entry is sodium dependent, sodium doesn't necessarily bring glutamine along with it when it enters the muscle cell. In other words, sodium entry is not dependent on glutamine. While sodium can freely leak into the muscle, the process by

There are several reasons why glutamine entry into the muscle is blocked after a workout. For one thing, high Cortisol levels will impair it.

When Cortisol is high, all glutamine stores become depleted. It's important to keep your Cortisol level under close scrutiny, as there's no way a dietary intake of amino acids or glutamine can counter its powerful negative influence.

which it is pumped out of the cell is energy, or ATP, dependent.

Unfortunately, ATP levels are reduced in the postworkout period, so the pump can't eliminate the sodium as fast as is required. The sodium loading ultimately translates into the slight muscle swelling that's apparent in the few days following a workout. It means that muscle glutamine entry is impaired—or at least slowed—not only during the workout but also for a long time afterward. That contrasts with the glutamine wasting, which is high during the same period.

Cortisol: Glutamine's Most Dangerous Enemy

Although a normal basal Cortisol level can participate in muscle growth, an excess impairs the process. Intense training tends to bring you closer to that dangerous threshold. When Cortisol is high, all glutamine stores become depleted. Cortisol forces your intestine and liver to increase their glutamine consumption, and it works with glucagon in the liver to destroy the glutamine. On top of that, Cortisol favors sodium accumulation in the muscle, which may explain in part why Cortisol severely impairs glutamine entry into the muscles while accelerating its exit. The result is a depletion of muscle glutamine in addition to the depletion caused by training. Consequently, it's important to keep your Cortisol level under close scrutiny, as there's no way a dietary intake of amino acids or glutamine can counter its powerful negative influence.

Insulin Transports Glutamine

If some hormones cause glutamine depletion, others have the opposite effect. Insulin is your first ally in glutamine manipulation. Glutamine is one of the few amino acids whose entry into the muscle can be enhanced by insulin, and you can certainly see the advantage of that. Any attempt to load up on glutamine should take advantage of the insulin-booster effect.

Some of the favorable actions of insulin are brought about by its influence on sodium. Insulin helps your muscles get rid of the extra sodium, which is a very interesting property in light of the sodium invasion that follows training. What's more, the anabolic effects of insulin and glutamine reinforce each other and can only be maximum when both are present.

The Mighty GH

Growth hormone (GH) was made to work along with glutamine, and vice versa. Bodybuilders have long been aware of the close relationship between the two because of the fact that oral glutamine can increase GH.1 On the other hand, they may not be aware that GH also increases glutamine levels in both blood and muscles without the ne-

cessity of any particular dietary change. Therefore, GH is truly the mighty ally you're looking for in glutamine manipulation.

One of the ways GH works is to limit the wasting of glutamine in the liver, where it can be transformed into urea. The urea is ultimately excreted in the urine, which means the glutamine is wasted simply because there's a catabolic process at work. Research has shown that GH shunts the "extracted glutamine nitrogen from urea via hepatic gluta-mate release."3 The newly formed glutamate can be transformed into glutamine in the muscle. So, instead of allowing glutamine to be urinated as a waste product, GH favors the recycling of it.

GH also has another major preserving effect on glutamine in the kidneys. As discussed in Part 1 of this series, one of the reasons glutamine degradation is accelerated after training is that lactic acid accumulates in the blood. That lowers plasma pH and forces the kidneys to extract circulating glutamine at a very fast pace. GH helps your kidneys to get rid of the acid load and as a result reduces their need for glutamine.4 Oral glutamine synergizes with GH at that point, not only by increasing the GH level but also by helping the hormone get rid of the acid that's generated by training.1 Other favorable effects of GH on glutamine are brought about indirectly by the elevation of insulinlike growth factor (IGF-1), a peptide that shares many of the positive actions of insulin on glutamine.

Testosterone Boosters to the Rescue

Research has shown that an elevation of androgen spares muscle glutamine content in catabolic situations. While part of that action of testosterone is likely to be direct, androgen precursors will synergize with many of the hormones discussed above as well. A good GH booster will work well with testosterone. Phosphatidylserine and vitamin C, which help control the secretion of Cortisol, will synergize with the prohormones to prevent the glutamine-wasting actions of corticoids.

Techniques for Glutamine Manipulation

Effective glutamine manipulation will include three distinct steps:

  1. Reduce the training-induced glutamine wasting.
  2. Refill the glutamine stores to prevent a shortage of glutamine.
  3. Attempt glutamine loading.

The first two steps are meant to combat some of the catabolic effects of training and enhance recovery. The third step is more aggressive, as it attempts to boost anabolism through dietary and endocrine manipulation rather than training. In fact, it tries to duplicate what you're already doing with creatine.

Here's a rundown of how to take those steps.

1) Reduce the training-induced glutamine wasting. At this point your best ally is the carb drinks. Blood glucose levels tend to fall during

Research has shown that GH shunts the "extracted glutamine nitrogen from urea via hepatic glutamate release." The newly formed glutamate can be transformed into glutamine in the muscle. So, instead of allowing glutamine to be urinated as a waste product, GH favors the recycling of it.

Drinking a casein drink or a casein-and-whey formula before a workout ensures the slow but long-lasting release of both glutamine and BCAAs while you train. If you can afford a glutamine supplement, use it before, rather than during, your workout.

  1. As a result, insulin secretion is repressed while the secretions of Cortisol and glucagon are enhanced. You want to reverse the situation, which is easily accomplished by increasing your carb intake before your workout and using a carb drink through the session. Studies have shown that carb drinks boost glutamine output at the end of a workout by cleaning out many of the waste products that accumulate in the muscles during exercise. That's a double advantage you shouldn't neglect. A preworkout stack of both GH and testosterone boosters along with phosphatidylserine and vitamin C will enable you to go beyond what you can achieve with a simple dietary manipulation.
  2. Refill the glutamine stores to prevent a shortage. The proteins derived from casein are usually the richest in glutamine; however, many manufacturers of whey supplements add extra glutamine to their proteins to make up for the comparative disadvantage. Drinking a casein drink or a casein-and-whey formula before a workout ensures the slow but long-lasting release of both glutamine and BCAAs while you train. If you can afford a glutamine supplement, use it before, rather than during, your workout. If you're on a tight budget, though, skip the glutamine at this point in your supplement schedule. Oral BCAAs are cheaper and more appropriate to the situation. As glutamine precursors, they're rapidly transformed into glutamine in the muscles. BCAAs have the advantage of building up the glutamine stores while bypassing the intestine barrier and the problem of getting into the muscle.2

Once your workout is over, have a shake made of fast-acting whey protein instead of going home with an empty stomach. If your whey is reinforced with glutamine, it's not crucial that you also take glutamine pills at this point either. The protein drink will combat the short-term post-training glutamine depression.6 I like to add creatine in order to help refill muscle ATP, which will be essential for the transport of muscle glutamine.

You should eat a normal meal 30 to 45 minutes after your post-train-ing protein drink. If you train in the morning, you can have a meal rich in both proteins and carbs. If you train at night, you want to be very careful about your carb intake at that hour if you want to remain reasonably lean. That's where glutamine pills can come in handy. To help your body fight the training-induced long-term wasting, take two grams of glutamine every hour for four hours—and skip the BCAAs, as they're said to compete with glutamine for entry into the muscle. You can help accelerate the entry of glutamine into the muscle by also using compounds that help accelerate the pumping of sodium out of the cell. Insulin release after carb intake is one.

3) Attempt glutamine loading. This may well be the most controversial aspect of the process. Is it possible to load your muscles with glutamine to force them to grow? Most specialists would agree that it's very hard to boost glutamine beyond normal levels in the muscles. A simple dietary ingestion of it is bound to produce limited results because of the absorption and muscle-entry problems. The experts usually recommend very high doses of glutamine to bypass those problems. The high doses reflect the limitations of our knowledge about the amino. The powerful effects of GH demonstrate that relatively small doses of glutamine can boost muscle glutamine considerably. Until science provides us with more appropriate tools for delivery, however, taking high doses of at least 15 grams a day is the only way to go.

In a very recent study researchers were able to load subjects' muscles with glutamine without increasing glutamine doses. Instead, they used a very interesting compound called dichloroacetate (DCA).7 Under various conditions DCA can increase muscle performance in humans. It did increase muscle glutamine levels rapidly. That's the good news. The bad news is that it was used on burn patients and failed to increase protein synthesis. Nevertheless, it is certainly a very promising compound for bodybuilders.

Here are some key points about glutamine to remember:

  • GH is of utmost importance for preserving glutamine and loading the muscles with it.
  • Insulin accelerates glutamine transport, which is usually a rate-limit-ing step.
  • You must keep Cortisol levels under control, or your dietary glutamine will all be wasted.

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 Welbourne, T. (1998). An oral glutamine load enhances renal acid secretion and function. Am J Clin Nutr. 67:660.

2 Wu, G. (1998). Intestinal mucosal amino acid catabolism. J Nutr. 128:1249.

3 Welbourne, T. (1989). Growth hormone effects on hepatic glutamate handling in vivo. Am J Physiol. 257:E959.

4 Welbourne, T. (1991). Growth hormone accelerates tubular acid se-cretion. Am J Physiol. 260: R1036.

5 Galassetti, P. (1998). Enhanced muscle glucose uptake facilitates nitrogen efflux from exercised muscle. JAppl Physiol. 84:1952.

6 Saris, W.H.M. (1997). Ingestion of drinks containing protein hy-drolysate prevents the postexercise reduction of plasma glutamine. IntJ Sports Med. 18: S115.

7 Ferrando, A.A. (1998). Acute dichloroacetate administration increases skeletal muscle free glutamine concentrations after burn injury. Ann Surg. 228:249.

  • GH is of utmost importance for preserving glutamine and loading the muscles with it.
  • Insulin accelerates glutamine transport, which is usually a rate-limiting step. •You must keep Cortisol levels under control, or your dietary glutamine will all be wasted.
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