GLUTAMINE: Once and for all?

GLUTAMINE

“Once and for all…should I spend my cash on a glutamine supplement or not?”

Do you think glutamine is a waste of money?

Can you get more than enough glutamine from the protein in ‘regular’ food?

If you’ve tried glutamine supplements before and never noticed a damn thing, is it just because you’re using it wrong?

I don’t have sh*tty muscle-building genetics. I just need to take more [insert name of dietary supplement here]!

Whatever.

“Glutamine supplements a ‘waste’? Impossible!”

-Anonymous

“Glutamine supplement ads are ‘much ado about nothing’? All hype, and no real substance? Outrageous! Preposterous!”

-Same guy as above

How in the world can you do without glutamine supplements?

Consider the scientific ‘facts’, if you will…

General stuff about glutamine:

n Glutamine is the most abundant (and arguably the most ‘popular’) amino acid inside your body. This extends to both the busy microscopic ‘ocean’ inside your cells (i.e. intracellularly) and the fluid which bathes them (i.e., extracellularly)(de Vasconcelos and Tirapegui, 1998)

n Glutamine and taurine (another frequently misrepresented amino acid) make up more than half of the pool of ‘free’ (i.e., non-protein-bound) amino acids floating about inside skeletal muscle (Bergstrom et al., 1974; Hankard et al., 1995). On a whole-body level, muscle represents about 50-80% of the free amino acid pool.

n A 70-kg man may release anywhere from 60-100 g of glutamine into the circulation per day (Nurjhan et al., 1995). Wow.

n The intracellular concentration of glutamine has been estimated to be around 20 mmol/L (Bergströmet al. 1974). What does that mean? Well, I lost the study that says exactly how much glutamine is outside the cell, but I can tell you that it means that there’s at least 30-fold more glutamine intracellularly than extracellularly. That’s a pretty steep concentration gradient. No wonder it’s so hard to push any more glutamine into your muscle fibers! (Oops! I wasn’t supposed to make remarks like that just yet…)

n What tissues make glutamine? Quite a few: skeletal muscle, brain, heart, lungs, skin, and adipose (fat) tissue (van Acker, 1999). Muscle contains more glutamine synthetase activity than that of glutaminase. Both are enzymes, that is, they are molecules (proteins, in fact) that help make certain biochemical reactions possible. Glutamine synthetase, as its name suggests, is a glutamine ‘maker’. Glutaminase, as its name suggests only to biochemistry students, is a glutamine ‘breaker’. It catabolizes, or degrades, glutamine. This means that muscle tissue is a net producer of glutamine. It ‘spits’ out plenty of it all day long.

n Glutamine synthetase is responsible for connecting ammonia (NH3) to glutamate to yield glutamine. The ammonia for this reaction can be derived from the breakdown of branch-chained amino acids (BCAAs)(yet another unnecessary dietary supplement for the healthy bodybuilder)(Oops! There I go again. I’m sorry. That was rude.)

n As the term ‘synthetase’ only suggests to biochemistry students, the coupling of ammonia to glutamate by glutamine synthetase requires energy, which is supplied by adenosine triphosphate (ATP, the key ‘energy currency’ of all cells). Thus, when blood levels of ammonia rise, BCAA levels may fall as the activity of glutamine synthetase increases. This means that glutamate levels inside the cell may fall. The free pool of glutamate can be replenished by breaking down more BCAAs via so-called ‘transamination’ reactions. What’s that mean? Nothing very important to you or I.

n Glutamine is a ‘conditionally essential’ amino acid, or at least that’s how some scientists describe it. What this means is that under some conditions the demand for it can become oh so great that you just have to supply more of it in the diet, or bodily function will begin to suffer. Are ‘some conditions’ the kind of situations that healthy bodybuilding consuming copious amounts of protein need be concerned about? No. (Okay…the cat’s out of the freaking bag at this point. What the hell…)

n If your muscles are always releasing glutamine, how do they maintain glutamine balance, i.e., avoid running ‘perpetually empty’ on glutamine? Well, under normal conditions, skeletal muscle produces glutamine via de novo synthesis (i.e., glutamine synthetase, BCAA catabolism, coupling of glutamate to ammonia) and by breaking down muscle proteins (not necessarily just myofibrillar) to release their bound glutamine (Mittendorfer et al., 1998). Hence the proposed ‘anti-catabolic’ effects of glutamine. Sure. Okay.

n In the fasted state, some ~70% of glutamine turnover (breakdown and synthesis) can be attributed to muscle. About 60% can be attributed to de novo glutamine synthesis. I lost the references for these points. Just pretend they’re false if you like. By the way, these are estimates, and they involve a bunch of complicated (certainly over my head) assumptions, some of which could be flat out wrong.

Stuff about Glutamine and Glucose

n Glucose is your body’s favorite fuel –top fuel on the totem pole, as I say. Many of you already know that glutamine can be converted into glucose. If you didn’t, you do now. Glutamine and alanine are the 2 key ‘glucose-generating’, or glucogenic, amino acids. The body seems to churn through more glutamine for this purpose each day than it does alanine (Nurjhan et al., 1995; Stumvoll et al., 1999). Is this one of the reasons why we don’t see too many alanine supplements being pushed on us? Or is that in the works? For the consumer’s sake, I hope not.

n Gluconeogenesis is one hell of an ugly name for one hell of an important biochemical process. In particular, it is that process by which glucose is made ‘from scratch’ (de novo), using, appropriately enough, things other than glucose (i.e., amino acids, glycerol, lactate). Glutamine stimulates gluconeogenesis, and, perhaps not surprisingly, the synthesis of glycogen (Bowtell et al., 1999). Glutamine can be a major source of glucose for the synthesis of both skeletal muscle and liver glycogen, such as following exercise (Bowtell et al., 1999).

n In fact, according to some researchers, glutamine occupies a major role as a source of carbon with which to maintain liver glycogen stores (Nurjhan et al., 1995). Wow.

n Thus, the following may not come as that much of a shock: After exercise, glutamine supplementation helps restore depleted glycogen stores in the liver and muscles (Varnier et al., 1995; Bowtell et al., 1999) about as effectively as carbohydrate. Five to eight grams (5-8 g) of glutamine seems to do the trick in healthy persons (Bowtell et al., 1999).

Stuff about Glutamine and Protein Anabolism

n The BCAA leucine is know to be a ‘potent’ stimulator of protein synthesis. NO big deal there, right? After all, as we know from “MELTING POINT” and “Macronutrient Balance” in Edition #1 of The ROB Report, neither food nor dietary supplements can actually bring about a net gain in myofibrillar protein mass –the essential element of making bigger muscles. Consequently, that glutamine may enhance leucine’s ability to stimulate protein synthesis, at least under some experimental conditions (Hankard et al., 1996 and references therein), isn’t really all that exciting, now is it?

n Not that glutamine can’t stimulate protein synthesis by itself, mind you. I remember once receiving some ‘scientific support’ materials from Bill Phillips many years ago (he probably forgot who I am) in which a quote very similar to the following had been highlighted, possibly by some hopeful marketing copywriter: “A striking correlation has been found to exist between the size of the glutamine pool in muscle and the rate of protein synthesis in this tissue.” True, at least in animals (Jepson et al., 1988). This observation has not been reported for any other amino acid, according to these authors.

Glutamine and Nitric oxide (NO): ‘Perpetual pumps?’

n Is there anything this amino acid can’t do? Glutamine is a key precursor to arginine (Windmueller and Spaeth, 1975; 1978). Arginine, in turn, is believed to be the physiological precursor to nitric oxide (NO). You’ve heard all the hype about NO as it pertains to the control of blood vessel diameter (vasodilation), among other things. (Read the Introduction to “I don’t NO” on my Web site under “Books” for more information.) Your muscles release glutamine, which the small intestine can then suck up, and use to synthesize citrulline. Citrulline gets shipped over to the kidney, where it is converted into arginine for NO production, among other fates.

L-Glutamine and Thermogenesis

n In healthy humans, glutamine affects a marked increase in energy expenditure when administered enterally (Hankard et al., 1996). Infusion of this amino acid was associated with a ~17% increase in resting energy expenditure (REE), from 1531 kcal/day to 1842 kcal/day. Glycine infusion, by contrast, produced no significant change in REE. Glutamine, but not glycine, was also shown to stimulate protein synthesis in the healthy subjects used for the study.

_nHankard et al. (1996) comment: “The present study suggests that, in healthy adult subjects, glutamine administration is associated with an increase in protein synthesis. The observed increase in resting energy expenditure with glutamine is consistent with such an increase in protein synthesis, as protein synthesis is an energy costly process. Assuming the cost of protein synthesis as 20% of energy expenditure, the 7% increase in protein synthesis should elicit a 1.4% increase in energy expenditure (0.20 x 7% = 1.4%); the increase in energy expenditure observed upon infusion of glutamine therefore cannot be entirely accounted for by enhanced protein synthesis.”

FINAL CONCLUSION

Protect your loved ones?

Now, I’m not a great copywriter. In fact, I consider my writing skills to be pretty poor. I spend an enormous amount of time just writing e-mails to people like you each day in an effort to help them with training and/or diet. I frequently edit my letters multiple times until they make sense, i.e., they are succinctly coherent and easy to navigate.

That being said, I could have taken many of the scientific ‘facts’ cited above and creatively weaved them into some pseudo-scientific tale of muscle-building hope, one that might have led you to leap for the phone (or get in the car) and purchase a crate of glutamine supplements for you and your loved ones. After all, you don’t want your muscles to wither away, do you?

Instead, I’m going to ‘exploit’ those scientific ‘facts’ in precisely the opposite manner. I’m going to use them as a foundation from which to explain why the ‘real’ foods you already consume –with or without any added protein supplements or meal-replacements (for convenience purposes only)— provide more than enough glutamine to suit even your wildest muscle-building desires. If you’re anything like me, those desires could be over-the-top…

First-hand experience

In wrapping this article up, let me state that I have experimented 'heavily' with glutamine over the years, beginning in the early 1990s. When I say ‘heavily’ I mean consuming it in what I would consider to be large gram quantities (e.g., 30-50 or more grams per day). Never have I noticed any positive effects on my body composition (i.e., muscle growth or fat loss) –the only reason I would consider taking glutamine in the first place.

This doesn’t really surprise me. I think some of you may already have a good idea why.

‘Real’ food is rich in glutamine

Well, for one thing, plant and animal matter suitable for human consumption --'real' food, in short-- is very rich in glutamine. Especially plant food.

The glutamine provided by the food you eat is almost completely broken down by your gut and liver --the 'gatekeepers', as I call them. Even when several grams of glutamine are infused into healthy humans, however, it doesn’t seem to affect muscle glutamine concentrations (e.g., Gore and Wolfe, 2003). This may have to do with that steep concentration gradient we learned about above.

Nevertheless, by feeding your gut and liver glutamine, it is theoretically possible to 'spare' peripheral glutamine-producing tissues (e.g., skeletal muscle, adipose tissue, lungs) the chore of having to produce glutamine for themselves. But again, viewed from that perspective, there’s absolutely no reason you need to take glutamine supplements, since regular foods contain a wealth of this amino acid.

We learned that your muscles can produce glutamine by breaking down (i.e., catabolizing) muscle proteins. These proteins may include, but are not limited to, myofibrillar proteins –the bodybuilder’s ‘Holy Grail’. Protein breakdown releases bound glutamine. Glutamine can also be made 'from scratch', i.e., de novo, such as by using materials obtained from the catabolism of branched-chain amino acids (BCAAs) and a little bit of glucose (for carbon). It’s for these reasons that glutamine is sometimes said to be ‘anti-catabolic’, or ‘muscle sparing’, but, again, the same could be said for any protein-containing food!

Eat more glutamine, burn more fat?

Hankard et al. (1996) provided evidence that enterally infused glutamine increases protein synthesis in healthy volunteers. I cited this paper earlier. Glutamine was also found to increase energy expenditure (~17%; from 1531 kcal/day to 1842 kcal/day). Glycine infusion, by contrast, produced no significant change in energy expenditure or protein synthesis.

You might expect that at least a portion of the 'thermogenic' effect of glutamine observed in the above study could be attributed to the stimulation of protein synthesis, an energy-expensive process, to be sure. I think another part of it was due to the stimulation of gluconeogenesis and glycogen synthesis --both of which glutamine may a more 'preferred' substrate for than glycine. More on this in a moment.

First let’s get this protein synthesis stuff out of the way. It’s stopping traffic. The Hankard et al. study does NOT suggest that glutamine supplementation will increase muscle protein synthesis, let alone muscle mass. We have no idea where in the body protein synthesis was actually being stimulated when these subjects consumed glutamine. Was glutamine stimulating protein synthesis in the gut? In the liver (e.g., incorporation into albumin for export to the periphery)? In the myofibrillar protein compartment of their muscle fibers (i.e., as bodybuilders and like-minded fitness enthusiasts would like)?

Wherever glutamine was increasing protein synthesis, who cares? After all, it will not affect a net gain in myofibrillar protein mass –the sin qua non of building bigger muscle fibers.

As you'll know from reading "Melting Point" in Edition #1 of The ROB Report, all glutamine, any other amino acid, or any food, can do is help you to maintain the myofibrillar protein mass that your muscle fibers establish in response to your workouts interacting against your particular genetic background. Only resistance training, hormones (and drugs that mimic them) can actually provoke a NET increase in myofibrillar protein mass. Again, this is the essential element of muscle fiber hypertrophy.

To repeat, food, protein supplements, glutamine supplements and the like only support the maintenance of whatever myofibrillar protein mass your battle with the weights manages to establish as it interacts with your genes.

Now back to glutamine and burning fat. Glucose is your body’s favorite fuel. One of the most important functions of glutamine is as a source of glucose. You know that your body can convert glutamine into glucose at a very high rate. This is partly why glutamine is such an essential amino acid, despite being 'non-essential' in the diet.

You may have heard me say that no diet is truly 'carbohydrate-free' --except, that is, a --'no diet' (starvation). For instance, every gram of protein you eat is made of amino acids --protein building blocks. Every one of those amino acids consists of an amino group (hence 'amino acid', except for histidine, which has an 'imino' group) attached to a carbon skeleton.

The carbon skeleton of a great many amino acids can be converted very nicely into glucose. Glycerol, which is found in the fat (triacylglycerol) stored on your body and in the food you eat, can also be converted into glucose, as can lactate (released by your muscles and other tissues).

It's because glucose is so essential to your very survival that human beings never lost the metabolic capacity to make glucose from 'non-carbohydrate' precursors --viz., amino acids, glycerol, and lactate. This process is referred to as gluconeogenesis.

It's because of gluconeogenesis, in turn, that we can survive on a 'carbohydrate-free’ diet, i.e., a diet absent of sugars and starches (the conventional definition of ‘dietary carbohydrate’). It's because of gluconeogenesis that we can survive without eating --at least for a while!

Of the amino acids in the diet, glutamine and alanine are two key glucogenic (glucose-generating) ones. Again, glutamine is thought to be more important, quantitatively speaking, than alanine. Perhaps this is because glutamine was so very abundant in the natural diet of our ancestors. As noted above, it is particularly abundant in plant proteins, but also in animal proteins.

Being that it was (and still is) abundant in the diet, it kind of makes sense that the human body evolved the capacity to use glutamine as a gluconeogenic substrate, i.e., with which to produce glucose from. Partly because the body could not afford to do without glucose, it became necessary to maintain the ability to make glutamine de novo. De novo glutamine synthesis, furthermore, reduces the need for the release of protein-bound glutamine, as via the catabolism of muscle or other tissue proteins.

All of this explains why we don't need to consume glutamine in the diet. The human body as always had to make it on its own. It is, consequently, 'non-essential' in the diet, though eating it certainly helps. Thus, viewed from this perspective, nutrients that are ‘non-essential’ in the diet are in fact very essential to your survival.

After your workouts, glutamine can help restore reduced blood glucose and glycogen stores (liver, muscle). Since in this case glutamine is being used as an 'expensive' source of glucose, you may need to take it in the same magnitude of doses (i.e., many grams) as you would dietary carbohydrate. Thus, don't expect to notice anything significant from 500 mg or 1 or 2 grams. Concerning muscle glycogen, 5-8 grams of glutamine consumed post-exercise has been shown to enhance both liver and muscle glycogen re-synthesis (Bowtell et al., 1999).

As I’ve explained before, there is a solid thermodynamic argument to consuming an excess of protein, i.e., more protein than you need to build muscle with. Eating 2.5 grams of protein/kg of body weight (1.14 g/lb) each day will more than accomplish this. Since some of the excess amino acids can be converted into glucose via gluconeogenesis –a process that is fueled by the burning of fat—there may be a substantial fat-burning advantage to eating an ‘excess-protein’ diet.

Enter glutamine and your fat-burning metabolism. Wouldn’t taking a multi-gram ‘whack’ of glutamine post-workout help you recover your muscle and liver glycogen stores –restore your Glucose Economy (whole-body glucose supply) in general— with a fat-burning ‘kick’ to boot? Glutamine’s conversion into glucose, and glycogen, after all, costs energy, and that energy is supplied by the burning of fat. Some of the energy is lost as heat, of course –thermogenesis. Witness the Hankard et al. (1996) study.

Sure. Which brings us back to good ‘ole food. If glutamine can afford you with a fat-burning advantage as it restores your Glucose Economy, and there’s a ‘solid thermodynamic argument’ for why it can, then any whole food or, if you really relish convenience, just about any protein powder or meal-replacement, will more than suffice. Indeed many protein powders sold to consumers these days contain several grams (up to 5 or more) of protein-bound glutamine per serving. Not that this is any better than the glutamine in a chicken breast, a top sirloin steak (my favorite cut), or a bowl of yogurt or cottage cheese (or both, as I frequently do), mind you.

FINAL FINAL CONCLUSION (I mean it. This is really it.)

Folks, save your money for something truly useful. You don’t need glutamine supplements to build as much ‘fat-free’ muscle as humanly possible. You will not hinder your gains if you don’t supplement your diet with this amino acid.

If you eat enough protein (this is really easy to do), then you will get more than enough glutamine to support your muscle-building goals, provided you train properly. If you aren’t eating enough protein, then simply eat more.

I hope this article has provided you with some useful insights. Thanks very, very much for being kind enough to read it.

Respectfully,

Rob

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