What theSalespeople Don't Want You To Know:
Glutamine and Protein Synthesis ó 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 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 bodyís 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 wouldnít 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, donít 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 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 itís almost a sure bet that glutamine wonít do anything for additional glycogen storage under normal dietary situations.
Things That Mom Never Told You About Glutamine Supplementation
Itís 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 doesnít 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 youíre interested in glutamine for its effect on and strength, youíre 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 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 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 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 youíve never heard of most of these studies, and why everything youíve 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 donít work. Iíll 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 youíve been hit over the head with them). But then again, thatís why theyíre 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 donít, but we have to be able to let go of them once they're shown to be incorrect. This doesnít mean that we shouldnít believe new theories when they first come out; it just means that we have to be conscious about the fact that they arenít 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 wasnít 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 canít convince them otherwise.
Since then Iíve 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, which is why I didnít just try to convincingly show that glutamine wasnít as great as everyone thought; I tried to overwhelmingly demonstrate it.
Glutamine is good for hospital patients and rich people with money to waste. If youíre involved in resistance training and already have proper post workout nutrition, along with a moderate carb intake, then glutamine probably wonít do anything for you. In fact, none of the proposed theories dealing with glutamine supplementation have worked out in the athletic world. Itís also one of the most expensive supplements around (simply based on dosage recommendations), so itís way too costly to use for personal experimentation ó especially when the updated scientific literature doesnít support the theories.
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