Glutamine: The Basics
For those of you who are new to the concept of glutamine supplementation, you should know that it's a non-essential amino acid created largely by our muscles. It's also noteworthy that glutamine is the most abundant free amino acid in our bodies, comprising up to 2/3 of the muscle free amino acid pool.(13) This fact, coupled with the idea that muscle is the largest producer of this amino acid, could suggest that supplementation would be beneficial.
One potential problem with this is that glutamine is a non-essential amino acid (meaning that we don't have to consume outside sources containing this amino acid because our bodies can make it on its own), but this is where things get interesting: the use of glutamine by many different cells in our bodies is so great that there may be times when its use exceeds its availability, therefore glutamine has been termed a "conditionally essential" amino acid.(18)
This means that during times of physical stress the body may actually need glutamine from the diet to maintain proper cellular function. Clearly, activities such as resistance training constitute a physical stress on the body, which is one reason that athletes have been targeted for glutamine supplementation.
Another interesting fact about our muscles and glutamine is the issue of transport. For an amino acid to get into or out of our muscles, it has to be transported by specific carriers. Using these carriers, our muscle takes up amino acids according to demand from protein composition (i.e. what our muscles need the most), BUT amino acid release is NOT according to composition.
Alanine and glutamine can account for up to 50% of amino acid release from muscle despite accounting for only about 15% of total muscle protein.(31) Obviously, this is a huge discrepancy—which is normally made up for through glutamine production—but as mentioned earlier, during times of physical stress (i.e. exercise), the synthesis of glutamine is hindered. Everyone knows that lacking even one amino acid can hinder muscle growth, which fortifies the theory of glutamine supplementation by athletes.
Now that you're familiar with the basics behind glutamine supplementation, it's time to delve into the literature and pull out some more specific theories as to the beneficial effects of glutamine supplementation.
Glutamine and Muscle Mass
Interest first arose in glutamine as a supplement when it was found that glutamine enrichment elevated levels of protein synthesis in isolated rat muscles.(21) This isn't surprising since it's also been found that muscle protein synthesis levels can be correlated with free glutamine levels.(17) It's also been shown in vitro using rat skeletal muscle cells that glutamine may decrease protein breakdown.(22)
Additionally, we know that the anabolic/catabolic state of a muscle cell is related to it's hydration status—this simply means that cellular swelling has an anabolic or an anticatabolic effect on the affected cells (including muscle cells). Based on this, it's been found that glutamine supplementation may mediate cell swelling and therefore an anticatabolic effect through either increasing cell swelling or hindering cellular dehydration.(28)
Sure you say, these theories are all well and good in cell cultures or animals, but what about the human studies? Well, studies in humans indicate that glutamine supplementation may improve nitrogen balance in critically ill patients, as well as assist in the prevention of protein synthesis decreases following surgery (a HUGE physical stress) or following a 14-hour fast.(13, 12,24,13) There have even been a couple of studies done on resistance trained subjects (more on that a little later)!
Glutamine and Overtraining
We've all felt the scourge of overtraining: the lethargy, the sickness, and the lack of desire to train. Aside from the horrible feeling associated with overtraining, we also know that the longer we're out of the gym, the longer we go without any anabolic stimulus to our muscles. Based on this, another theory suggesting glutamine supplementation for athletes involves the prevention of overtraining.
Glutamine is used as a fuel source by many cells of our body, including many cells of our immune system. Now if you recall that there are times of stress where the body's production fails to meet its needs for glutamine, you can see that this could negatively affect the immune system. In fact, you may not be surprised to find that blood glutamine levels may be compromised following exercise induced overtraining.(1)
Surveys of endurance athletes supplementing with glutamine following a marathon race showed lower rates of infection than those who didn't supplement.(8,9) As for the applicability to bodybuilding, one study showed that resistance exercise may induce a small transient (ie short-term) negative effect on some cells of the immune system, although plasma glutamine levels weren't examined.(6)
So now we have theories for glutamine supplementation to increase protein synthesis/inhibit protein breakdown, as well as boost immunity following intense exercise. This sounds great, but we have yet to look at glutamine's potential effect to stimulate glycogen replenishment following exercise. Glutamine infusion has been shown to enhance glycogen stores following cycling exercise twice as much as compared to subjects who infused saline or other amino acids.(27) If this happened after weight training, it could even help with our cellular swelling and have the aforementioned postive effect on protein accretion.
Another study supports the use of glutamine for enhancing muscle glycogen. Bowtell et al. found that glutamine supplementation following exercise enhanced glycogen resynthesis in muscle just as well as the ingestion of a glucose polymer.(4)
Sadly at this point, many readers have already gone out and bought their kilos of glutamine, and are now reading only to find out how to use the stuff. You may argue, why not? There's plenty of evidence to support the theories presented! This was exactly the thinking when glutamine was introduced to bodybuilders several years ago. In fact, the journal articles reviewed above are the same research papers that can be found time and again, in any outdated article that's trying to sell you on glutamine. But things have recently changed; new studies have been done on animals, and people involved in resistance training, but the results are less than positive.
What the Glutamine Salespeople Don't Want You To Know:
Glutamine and Protein Synthesis — The other side of the coin
We've seen the theory that glutamine levels in the blood and muscle may decrease during or following exercise, and that this decrease correlates with reduced levels of protein synthesis. Several studies have addressed whether this relationship between glutamine and protein synthesis was a coincidental or a causal (meaning that one caused the other) relationship.
The first study compared the abilities of glutamine and the amino acid alanine to stimulate protein synthesis in rats with artificially reduced blood and muscle glutamine levels.(23) As expected, glutamine infusion increased intramuscular glutamine levels, while alanine didn't. Surprisingly, even depleting muscle glutamine levels by 60% had no effect on protein synthesis. What may also surprise you is that restoring blood and muscle glutamine levels to normal had no effect on protein synthesis compared to rats receiving no glutamine treatment! Additionally, even though whole body protein turnover didn't change, alanine stimulated protein synthesis!
In support of this contention, researchers studied the effect of glutamine supplementation on septic rats. Sepsis is a severely catabolic condition, during which glutamine levels (and protein synthesis) fall. Again, this study showed that despite increasing muscle glutamine levels to even higher than normal, it had no effect on protein synthesis or the catabolic state of the rats.(11)
Cumulatively, these studies show that decreased or increased levels of glutamine in the muscle has no effect on protein synthesis.
Another study, performed on people, examined the effect of adding glutamine to an amino acid mixture on muscle protein synthesis .(30) Ultimately, infusion of the original amino acid mixture increased protein synthesis by nearly 50%, but adding glutamine to this mix had no additional effect. This study is particularly relevant because most consumers of glutamine do so following a workout, along with other amino acids (or a whole protein).
Finally, Wusteman et al., used a drug to reduce muscle protein synthesis, along with muscle glutamine levels, in rats.(29) Much like the Olde Damink et al. study, restoring muscle glutamine levels to normal had no effect on protein synthesis. This study further supports the concept that blood and muscle glutamine levels have no bearing on protein synthesis and protein turnover.
Another One Bites the Dust
You may recall that the theory of exercise induced immunosuppression is often cited, based on the fact that glutamine levels decrease after exercise, as does our immunity.(10)
What we must now address is whether the relationship between the body’s glutamine stores and the effects of exercise on the immune system exhibit a causal or coincidental relationship (just as we did for protein synthesis). A recent review article in "The Journal of Applied Physiology" examined this connection between plasma glutamine and exercise-induced immunosuppression.(15)
The study admitted that there are conflicting reports about plasma glutamine levels following long duration exercise, repeated high intensity bouts, as well as short single high intensity bouts. This indicates that plasma glutamine concentrations may be affected differently depending on the intensity and duration of exercise.
Even data on blood glutamine concentrations following eccentric exercise is mixed, which can relate directly to bodybuilders and their use of heavy loads. Based on the relatively small reductions in plasma glutamine that might occur following exercise, supplementation with glutamine wouldn’t likely affect the immune cells.
More importantly, there are several studies showing that glutamine supplementation doesn't alter exercise-induced suppression of the immune system! The bottom line is that blood glutamine levels, whether they drop or not following exercise, don’t seem to affect immunity to any great extent, which precludes the use of glutamine for this reason.
Another recent review looked at over 75 research papers pertaining to the effect of glutamine on immunity and muscle growth, and came to the following conclusion: "Overall, although glutamine obviously plays important metabolic roles within the body, supplementation does not appear to provide consistent beneficial or therapeutic effects, except during certain catabolic situations. Glutamine availability, therefore, does not seem to be a limitation in many challenge situations."(19)
What about the glycogen?!
Yep, we have one final theory to validate spending God-awful amounts of money on glutamine; that of enhanced glycogen resynthesis following our workouts. In addition to the aforementioned studies showing better glycogen storage, there is also a study showing no effect of oral glutamine on glycogen regeneration following high intensity interval training.(26)
This issue was actually addressed by the authors of the Candow study, who found no strength or mass changes in trained individuals using glutamine (versus a placebo).(7) They suggested that the studies done showing enhanced glycogen recovery used exercise bouts which depleted intramuscular glycogen by 90%(!), while resistance exercise only depletes muscular glycogen by ~36%.
The bottom line is that the jury is still out on glutamine enhancing glycogen resynthesis following resistance exercise, but it seems unlikely that it would have any effect. Toss in the huge amounts of high glycemic carbs that most of us use following our workouts, and it’s almost a sure bet that glutamine won’t do anything for additional glycogen storage under normal dietary situations.
Things That Mom Never Told You About Glutamine Supplementation
It’s important to examine the method used for getting glutamine into the body in the human studies presented. Unfortunately, getting glutamine into our blood and to our muscles is a lot harder than one may expect. It was mentioned earlier that many cells of the body use glutamine for fuel. Well one area of cells that just loves glutamine is the gastrointestinal tract. In fact, it can account for up to 40% of glutamine utilization in the body! Now figure out the first area to come into contact with our "wonder supplement," and you can see that you have to take a whole crap-load of the stuff all at once, just so our gut doesn’t use it all!
Now, dumping 20g of one amino acid into our bodies at once may sound fun to some, but then again we can safely call these people masochists. For the rest of us, this huge glutamine dump may lead to some GI distress, which we all know is NOT fun.
Fortunately, the two studies performed with bodybuilders using relatively high dosages of glutamine (0.3g/kg/d and 0.9g/kg lean mass/d) reported no side effects of any kind.(2, 7) What is unfortunate is that the authors of these studies also showed no positive effect of any kind!
Glutamine and Resistance Trained Athletes: The Studies
One recent study examined the effect of acute glutamine ingestion on weightlifting performance.(2) This study examined the potential buffering effect of glutamine on lactic acid production during resistance exercise (to the point of momentary muscular failure).
One hour following glutamine ingestion (0.3g/kg), glycine ingestion (0.3g/kg), or placebo drink ingestion, the trained subjects performed 2 sets each of leg press (@ 200% body weight) and bench press (@ 100% body weight). This would equate to an average of ~23g of either amino acid ingested all at once, but there were no reports of GI discomfort.
Each subject consumed one of the three supplements before three separate testing sessions separated by a week. There was no effect of glutamine on number of reps performed compared to glycine or placebo ingestion. These results indicate that a high dose of glutamine ingested before exercise has no positive or negative effects on weightlifting performance in trained subjects.
If you’re interested in glutamine for its effect on muscle mass and strength, you’re in luck because a study was done on that, too! This next study is undoubtedly one of the best kept secrets in bodybuilding! In this study, the trained subjects consumed either 0.9g/kg lean body mass/day (average of 45g/day!), or a placebo, in 2 divided doses.(7)
It's noteworthy that using this amount of glutamine would run over 1200$USD per year for a 200lb guy!
By the end of the 6-week period, there were no differences in terms of 1Rep Max on squat or bench between the groups. There were also no differences between groups when it came to the gains in lean body mass (i.e. the amount of muscle they put on) during the trial period. This study was well designed and used the highest amount of glutamine ever studied for these purposes.
Glutamine Ain't All That Bad
After kicking the crap out of glutamine for most bodybuilding purposes, it is important to realize that there are certain situations where glutamine can be useful.
A recent study from the journal "Metabolism" shows that glutamine injections following glucocorticoid (ie catabolic steroid -such as cortisol) treatment can increase protein synthesis in the gastrointestinal system of dogs.(16) Unfortunately, nonoxidative leucine disposal, a measure of whole-body protein synthesis, remained unchanged in the glutamine treated group.
There are a dozen ways you could interpret these findings, but at least we can say that glutamine supplementation may improve protein synthesis in some tissues following gluccocorticoid treatment. In fact, glucocorticoid treatment is one area where glutamine supplementation may really help!
Another study with rats supports this contention, again using corticosteroid administration.(14) Although glutamine infusion had no effect on muscle protein synthesis in the rats not receiving cortisol, there was a beneficial effect in the glucocorticoid treated rats. In fact, glutamine infusion actually attenuated more than 70% of the muscle wasting caused by the cortisol injections!
Along these lines, certain catabolic conditions (such as sepsis) may be another useful situation in which glutamine could help out. One literature review clearly concluded that "The increased intake of glutamine has resulted in lower septic morbidity in certain critically ill patient populations."(3) This means that people with certain catabolic medical conditions may live longer when taking glutamine. Keeping this in mind, we also know that AIDS can be associated with muscle wasting. Recent evidence has arisen to demonstrate that glutamine supplementation may attenuate AIDS-induced muscle wasting.(25)
Overall, these studies show that glutamine could be very helpful for muscle mass during corticosteroid treatment and certain wasting conditions. For those of you who think that your everyday training may be intense enough to simulate a catabolic condition, keep in mind that these people are dying because of their catabolism, so you're really no where near that level.
The only time a bodybuilder even remotely approaches these kind of catabolic conditions is when improperly coming off a cycle of anabolic steroids. In this situation the user has minimal anabolic stimulus from Testosterone and a large amount of cortisol just waiting to eat that muscle (again, this is only when done improperly). In this situation, glutamine supplementation might help, but it's not a situation you should be in anyway.
The other time that glutamine supplementation may be beneficial to bodybuilders is when on a low carbohydrate diet. Glutamine can not only be converted to glucose, but may also have an anapleurotic effect.(5) In other words, it may replenish metabolic intermediates, in this case, ATP (especially important when you're lacking carbs). This is another article unto itself, so I'll leave it at that for now.
You may be asking why you’ve never heard of most of these studies, and why everything you’ve heard about glutamine was always so amazing. I can indirectly answer that by reminding you of one simple fact: no one makes money by showing that supplements don’t work. I’ll leave the rest of the thinking on this matter to you.
Despite this, you may still be skeptical regarding the points mentioned, based on the original dogmatic theories associated with glutamine use (and how long you’ve been hit over the head with them). But then again, that’s why they’re just theories. To paraphrase Homer Simpson: "Sure it may work in theory, but then again even communism works...in theory."
It's the mark of a great person who can devise a theory, drawing from many different ideas, and stick to it. Without this, science would be meaningless. But it's the mark of an even greater person when they can admit, without shame, that their idea is wrong.
Sometimes theories pan out and sometimes they don’t, but we have to be able to let go of them once they're shown to be incorrect. This doesn’t mean that we shouldn’t believe new theories when they first come out; it just means that we have to be conscious about the fact that they aren’t dogma and may be wrong.
Case in point: The theory behind glutamine was so great that I refused to believe the authors of the Candow et al. (2001) study when they told me the results in person. I was an educated bodybuilder and I wasn’t going to let some egghead scientist (who was actually more muscular than I was, and therefore far from being just an "egghead") tell me that I was wrong. Of course, I wanted to believe that glutamine was useful (even though I got nothing from it) and when someone wants to believe something you can’t convince them otherwise.
Since then I’ve had a while to let the results sink in. I know that most believers in glutamine will also have a hard time accepting the reality of the situation
Glutamine is good for hospital patients and rich people with money to waste. If you’re involved in resistance training and already have proper post workout nutrition, along with a moderate carb intake, then glutamine probably won’t do anything for you. In fact, none of the proposed theories dealing with glutamine supplementation have worked out in the athletic world. It’s also one of the most expensive supplements around (simply based on dosage recommendations), so it’s way too costly to use for personal experimentation — especially when the updated scientific literature doesn’t support the theories.
David J. Barr, CSCS, MSc. Candidate, is a Varsity Strength and Conditioning Coach at the University of Waterloo. You can contact him at firstname.lastname@example.org
1. Antonio J, Street C.
Glutamine: a potentially useful supplement for athletes. Can J Appl Physiol 1999 Feb;24(1):1-14
2. Antonio J, Sanders MS, Kalman D, Woodgate D, Street C.
The effects of high-dose glutamine ingestion on weightlifting performance. J Strength Cond Res 2002 Feb;16(1):157-60
3. Boelens PG, Nijveldt RJ, Houdijk AP, Meijer S, van Leeuwen PA.
Glutamine alimentation in catabolic state. J Nutr 2001 Sep;131(9 Suppl):2569S-77S; discussion 2590S
4. Bowtell JL, Gelly K, Jackman ML, Patel A, Simeoni M, Rennie MJ.
Effect of oral glutamine on whole body carbohydrate storage during recovery from exhaustive exercise. J Appl Physiol 1999 Jun;86(6):1770-7
5. Bruce M, Constantin-Teodosiu D, Greenhaff PL, Boobis LH, Williams C, Bowtell JL.
Glutamine supplementation promotes anaplerosis but not oxidative energy delivery in human skeletal muscle. Am J Physiol Endocrinol Metab 2001 Apr;280(4):E669-75
6. Bush JA, Dohi K, Mastro AM, Volek J, Lynch JM, Triplett-McBride, Putukian M, Sebastianelli WJ, Newton RU, Hakkinen K, Kraemer WJ. Exercise and recovery responses of lymphokines to heavy resistance exercise J Str Cond Res 2000 14(3) 344-349
7. Candow DG, Chilibeck PD, Burke DG, Davison KS, Smith-Palmer T.
Effect of glutamine supplementation combined with resistance training in young adults. Eur J Appl Physiol 2001 Dec;86(2):142-9
8. Castell LM, Poortmans JR, Newsholme EA.
Does glutamine have a role in reducing infections in athletes? Eur J Appl Physiol Occup Physiol 1996;73(5):488-90
9. Castell LM, Newsholme EA.
The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise. Nutrition 1997 Jul-Aug;13(7-8):738-42
10. Castell LM.
Can glutamine modify the apparent immunodepression observed after prolonged, exhaustive exercise? Nutrition 2002 May;18(5):371-5
11. Fang CH, James JH, Fischer JE, Hasselgren PO.
Is muscle protein turnover regulated by intracellular glutamine during sepsis? JPEN J Parenter Enteral Nutr 1995 Jul-Aug;19(4):279-85
12. Hammarqvist F, Wernerman J, von der Decken A, Vinnars E.
Alanyl-glutamine counteracts the depletion of free glutamine and the postoperative decline in protein synthesis in skeletal muscle. Ann Surg 1990 Nov;212(5):637-44
13. Hankard RG, Haymond MW, Darmaun D.
Effect of glutamine on leucine metabolism in humans. Am J Physiol 1996 Oct;271(4 Pt 1):E748-54
14. Hickson RC, Czerwinski SM, Wegrzyn LE.
Glutamine prevents downregulation of myosin heavy chain synthesis and muscle atrophy from glucocorticoids. Am J Physiol 1995 Apr;268(4 Pt 1):E730-4
15. Hiscock N, Pedersen BK.
Exercise-induced immunodepression- plasma glutamine is not the link. J Appl Physiol 2002 Sep;93(3):813-22
16. Humbert B, Nguyen P, Dumon H, Deschamps JY, Darmaun D.
Does enteral glutamine modulate whole-body leucine kinetics in hypercatabolic dogs in a fed state? Metabolism 2002 May;51(5):628-35
17. Jepson MM, Bates PC, Broadbent P, Pell JM, Millward DJ.
Relationship between glutamine concentration and protein synthesis in rat skeletal muscle. Am J Physiol 1988 Aug;255(2 Pt 1):E166-72
18. Lacey JM, Wilmore DW.
Is glutamine a conditionally essential amino acid? Nutr Rev 1990 Aug;48(8):297-309
19. Lobley GE, Hoskin SO, McNeil CJ.
Glutamine in animal science and production. J Nutr 2001 Sep;131(9 Suppl):2525S-31S; discussion 2532S-4S
20. Low SY, Taylor PM, Rennie MJ.
Responses of glutamine transport in cultured rat skeletal muscle to osmotically induced changes in cell volume. J Physiol 1996 May 1;492 ( Pt 3):877-85
21. MacLennan PA, Brown RA, Rennie MJ.
A positive relationship between protein synthetic rate and intracellular glutamine concentration in perfused rat skeletal muscle. FEBS Lett 1987 May 4;215(1):187-91
22. MacLennan PA, Smith K, Weryk B, Watt PW, Rennie MJ.
Inhibition of protein breakdown by glutamine in perfused rat skeletal muscle. FEBS Lett 1988 Sep 12;237(1-2):133-6
23. Olde Damink SW, de Blaauw I, Deutz NE, Soeters PB.
Effects in vivo of decreased plasma and intracellular muscle glutamine concentration on whole-body and hindquarter protein kinetics in rats. Clin Sci (Lond) 1999 Jun;96(6):639-46
24. Petersson B, von der Decken A, Vinnars E, Wernerman J.
Long-term effects of postoperative total parenteral nutrition supplemented with glycylglutamine on subjective fatigue and muscle protein synthesis. Br J Surg 1994 Oct;81(10):1520-3
25. Shabert JK, Winslow C, Lacey JM, Wilmore DW.
Glutamine-antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial. Nutrition 1999 Nov-Dec;15(11-12):860-4
26. van Hall G, Saris WH, van de Schoor PA, Wagenmakers AJ.
The effect of free glutamine and peptide ingestion on the rate of muscle glycogen resynthesis in man. Int J Sports Med 2000 Jan;21(1):25-30
27. Varnier M, Leese GP, Thompson J, Rennie MJ.
Stimulatory effect of glutamine on glycogen accumulation in human skeletal muscle. Am J Physiol 1995 Aug;269(2 Pt 1):E309-15
28. Vom Dahl S, Haussinger D.
Nutritional state and the swelling-induced inhibition of proteolysis in perfused rat liver. J Nutr 1996 Feb;126(2):395-402
29. Wusteman M, Tate H, Elia M.
The use of a constant infusion of [3H]phenylalanine to measure the effects of glutamine infusions on muscle protein synthesis in rats given turpentine. Nutrition 1995 Jan-Feb;11(1):27-31
30. Zachwieja JJ, Witt TL, Yarasheski KE.
Intravenous glutamine does not stimulate mixed muscle protein synthesis in healthy young men and women. Metabolism 2000 Dec;49(12):1555-60
31. Zorzano A, Fandos C, Palacin M.
Role of plasma membrane transporters in muscle metabolism. Biochem J 2000 Aug 1;349 Pt 3:667-88