Glutamine Supplements: Beneficial or a Waste of Money

I remember when glutamine was one of the hottest supplements around. One of the go-to supplements for anyone interested in strength training, or in exercise in general for that matter. Not only could it make you bigger and stronger, it also kept the respiratory infections away and helped you recover faster after your grueling workouts.

Over the years, study after study revealed that glutamine didn’t really live up to the hype. Gains in muscle mass from glutamine supplementation turned out to be a thing only during severly catabolic states like sepsis and large-scale burns. Upper respiratory infections ignored your glutamine supplement and put you to bed anyway. Today, the hype has calmed down a bit.

What does the current scientific evidence have to say about glutamine supplements for gaining muscle mass and strength, your immune system and your performance? Keep reading and you will find out.

What is Glutamine?

L-glutamine, or simply glutamine for short, is a nonessential amino acid. This means that your body can make glutamine on its own without you having to supply it through your diet. Sometimes, glutamine is considered conditionally essential. Conditionally essential amino acids are amino acids that become essential under certain conditions.1

One example of such a condition is when you are exposed to a severely stressful or catabolic condition. We’re not talking about 10 sets of biceps curls here, but sepsis, critical illnesses, injuries or medical emergencies. During these conditions, your muscles are depleted of glutamine. The needs of your intestines and immune functions take precedence over your muscle protein synthesis. When this happens, your body can’t keep up and synthesize glutamine at the same rate that glutamine is depleted. A case of supply and demand, and the demand becomes larger than the supply. In other words, you need glutamine from outside sources.2

Not all scientists agree that glutamine is a conditionally essential amino acid, though. Some refer to it as a commercially essential amino acid and advice against a general recommendation of glutamine supplementation for therapeutic use, regardless of medical condition.3

Glutamine Synthesis and Function

Your body can produce glutamine on its own with a little help from an enzyme called glutamine synthetase. Glutamine synthetase acts like a catalysator for the condensation of glutamate and ammonia into glutamine, using energy from adenosine triphosphate. Glutamine is mostly synthesized in your muscles. From there, glutamine is transferred to other tissues in need of it. Your lungs, brain, and liver can also synthesize glutamine, although to a much lesser extent.

Glutamine might be the most versatile of all the amino acids. It plays a number of important roles, many of which are essential to keep your body in a functional state. Glutamine is a so-called proteinogenic amino acid, meaning that it is part of your protein turnover and is used to synthesize new tissue. In addition, glutamine regulates pH-levels in your body and is used as an energy source for many different cells. It also contributes nitrogen to a number of processes, and maintains the function and integrity of the mucous membranes in your gut and intestines. Just to mention some of the important bodily functions glutamine is involved with.

Glutamine is very important for your immune system. Glucose might be the main fuel for most of the cells in your body, but not for the cells of the immune system, like macrophages, lymphocytes and neutrophils. These all use glutamine as fuel to a larger extent than glucose during stressful situations.4

A low level of glutamine in the blood has a negative effect on your immune system. If this happens during extreme situations like sepsis, burns, or during extensive surgery, it leads to a higher risk of complications and even mortality.

The Most Abundant Amino Acid

Glutamine is the most abundant amino acid in your body. Normally, your body produces between 40 and 80 grams of glutamine per day.5 Glutamine turnover depends on the needs of your body. During stress and catabolic conditions, glutamine requirements increase, which in turn leads to an increase in both glutamine synthesis and breakdown.

A healthy person weighing about 70 kilograms has 70–80 grams of glutamine stored in his or her body at any given time.6 Glutamine levels are particularly high in the musculature and in the liver. Around 40–60% of the total amino acid pool in these tissues is composed of glutamine.7 In both your blood and other tissues, glutamine concentrations are 10–100 times higher than the concentration of any other amino acid.

Exercise and Your Glutamine Levels

Illness and trauma are not the only things that can reduce plasma glutamine levels. Long-duration and/or high-intensity exercise can, as well. Glutamine supplementation prevents this fall in plasma concentrations of glutamine. Almost 30 years ago, scientists took notice of this effect and postulated that taking a glutamine supplement pre- or post-exercise might help the immunodepression that occurs during recovery from physical exertion. Later research has failed to confirm this theory. The glutamine/immune system connection does not seem to be that simple, but more about that later. Supplement companies took these more or less vague associations and used them to claim that glutamine in supplement form can improve your training results in a number of ways.

Let’s take a look at how many of these claims have scientific evidence to support them.

Body Composition and Muscle Growth

Since glutamine constitutes such a large part of the amino acid content of your body in general and your muscles in particular, it is easy to assume that dietary or supplemental glutamine is important for building muscle.

However, research shows that you don’t need nonessential amino acids to stimulate muscle protein synthesis.8 If you add nonessential amino acids to a source of protein, like a protein shake or a regular meal, nothing extra happens.

This also applies to glutamine. In one study, young men received 0.3 grams of glutamine per kilogram of body weight along with carbohydrate and essential amino acids after a strength training session.9 A control group ingested the same amount of carbohydrate and amino acids. Following the workout, muscle protein synthesis increased significantly in both groups, but the added glutamine didn’t do anything.

Studies on the effects of glutamine on body composition and muscle protein synthesis aren’t limited to the hours following a workout.

A randomized double-blind placebo controlled study gave 31 young men either a massive daily dose of 0.9 grams of glutamine per kilogram of body weight or placebo in the form of maltodextrin over the course of 6 weeks. During this time, they followed a whole body resistance training program. The results after 6 weeks of training and supplementation showed a 2% increase in fat-free mass in both groups, with no significant differences between groups.10

In another randomized study, wrestlers received either placebo or 0.35 grams of glutamine per kilogram of body weight and day during 12 days of calorie deficit.11 The wrestlers lost body weight, body fat, and fat-free mass during these 12 days. Dual-energy X-ray absorptiometry did not show any differences between groups.

Two studies have suggested greater gains in fat-free mass while supplementing with glutamine during a strength training program, although these studies might not be quite as well-controlled and well-designed as we would prefer.

In one of them, previously untrained male students engaged in strength training 3 times per week over the course of 8 weeks.12 During this time, they also ingested either 0.35 grams of glutamine per kilogram of body weight and day or placebo. The glutamine group increased their fat-free mass a bit more, although this study didn’t measure changes in muscle mass specifically.

In the second study, the researchers gave either glutamine or placebo in the form of sugar to soccer players half an hour before training over the course of 8 weeks.13 The players who received glutamine improved their body composition more than those who got the sugar pill. However, this study has limitations like a small number of participants and the fact that body composition was measured using bioimpedance, a method with a larger margin of error than, for example, DXA.

A 2019 meta-analysis reviewed the studies mentioned above and a few more.14 After analyzing and compiling the results of all these studies, they found no association between glutamine supplements and either fat-free mass or body fat. They did find an association between glutamine and body weight. Supplementing with glutamine might reduce body weight a bit, but without changing the ratio between fat-free mass and body fat.

glutamine

In summary, you probably shouldn’t expect to gain any muscle mass or lose any body fat by supplementing with glutamine. In short: glutamine likely won’t improve your body composition.

Glutamine and Your Immune System

Upper respiratory infections are common in athletes undergoing intense and prolonged exercise, like marathon running. One of the causes behind the association between exhaustive exercise and infections could be the decline in white blood cells following training and physical exertion. Glutamine fuels white blood cells. Therefore, it seems like logical reasoning to assume that glutamine supplements might prevent both the fall of plasma glutamine and white blood cell count after a workout or a race.

Let’s say the observed fall in plasma glutamine after physical exertion is directly tied to a compromised immune system. You should then in theory be able to limit or prevent this effect by supplementing with glutamine before, during or after a workout.

An attractive thought. That would be a simple and cheap way to decrease the risk of catching a cold during intensive training. Research doesn’t really support it, though.

In one study, healthy men performed 3 cycling sessions in a row, separated by 2 hours of rest, at 75% of VO2 max.15 The sessions lasted 60, 45, and 30 minutes, respectively. After each session, they received 0.1 grams of glutamine per kilogram of bodyweight. The supplement prevented a decrease in plasma glutamine, as expected. However, it did not prevent a depressed white blood cell count or other markers of immune function.

Several other studies have investigated if supplementing with glutamine before and after prolonged exercise prevents a depressed immune system.16 17 18

Glutamine in amounts large enough to prevent the fall in plasma glutamine did nothing for various markers of immune function. Natural killer cells, a type of lymphocyte that contains viral infections while the immune system creates T cells that can clear them, decreased despite the glutamine. In addition, neutrophil count, an important part of the innate immune system, remained unchanged.

There are more studies than those. None of them have been able to consistently show reduced rates of colds and upper respiratory infections in athletes. Long distance runners did self-report fewer upper respiratory infections with a glutamine supplement than without, the week following a race.19 However, blood samples did not show any significant differences in leukocyte or lymphocyte count compared to placebo.

In summary, glutamine supplements probably won’t be able to help you avoid colds. The majority of the research fails to see an association between glutamine supplementation and markers for immune function and infection risk. A recent meta-analysis also concludes that glutamine does not influence white blood cell count and has no effect on the immune system of athletes.20

Glutamine and Physical Performance

Can glutamine help you perform better? Will glutamine supplementation allow you to run faster and longer, or to lift more and heavier?

Aerobic Training

Glutamine does not seem to have any effect on aerobic capacity, your ability to perform in activities requiring oxygen, like running, cycling, or any other aerobic, cardiovascular exercise. A meta-analysis found no evidence that supplementing with glutamine improves oxygen uptake, oxygen consumption, or energy expenditure in endurance athletes.21

Neither does glutamine increase your heart rate, which means that it can’t improve blood flow to your working muscles.

Anaerobic Training

As for anaerobic training, where we find strength training, there isn’t enough research to say anything for sure. The same meta-analysis was unable to reach any conclusion because of a lack of data.

However, if we take a closer look at individual studies, we find a number of them in which glutamine improves strength and power.

In one study, glutamine supplementation partially prevented loss of strength following muscle-damaging exercise in the form of 100 depth jumps. In addition, the glutamine group wasn’t as sore the days after the exertion.22

Another study demonstrated improved strength recovery following eccentric leg extensions, when the participants consumed a glutamine supplement.23

This hold true when we look at power indices. Twelve men performed a number of Wingate tests, and recovery markers improved significantly when they ingested glutamine compared to placebo.24

In a double-blind study, 28 male subjects ran 3 sprint interval sessions separated by an hour of rest. 25 Each session incorporated 6 35-meter sprints. Two hours before the sessions, the participants drank either water plus glutamine, water plus carbohydrate, water plus glutamine and carbohydrate, or placebo in the form of artificially sweetened water. The group who drank the water containing both carbohydrate and glutamine improved their performance the most. That group lost the least amount of anaerobic power as the sprint intervals progressed compared to the other groups.

At the same time, several studies have failed to reveal any improvements in strength, anaerobic performance, and vertical jump capacity after supplementing with glutamine compared to placebo.26 27

As you can see, the research isn’t conclusive. Some studies show performance improvements following glutamine supplementation, while others don’t. There simply isn’t enough data to say anything for sure. That is why the previously mentioned meta-analysis didn’t come to any conclusion. That being said, there is some research supporting glutamine as an ergogenic aid for anaerobic activities. However, there are few, in any, studies looking at regular strength training.

Even if it turns out that glutamine doesn’t improve anaerobic performance directly, it might still regulate mechanisms that do:

  • Glutamine functions as a buffer, possibly counteracting the muscle acidosis produced by exercise.28
  • Glutamine improves glycogen synthesis both in the muscles and in the liver following exercise.29 This means that you can recover faster after a hard workout. Another study failed to replicate those results, though.30
  • Glutamine supplementation seems to suppress plasma lactate levels during exercise, which could help performance.31

In summary: are you considering glutamine as a way to improve aerobic performance or to become a better endurance athlete? Forget it. Glutamine does not seem to have any such effect. When it comes to strength, power, and anaerobic performance, things aren’t as clear-cut. There isn’t enough qualitative evidence to say anything for sure. There are more studies suggesting some positive effects than there are studies finding no effect. Keep in mind that we are not talking dramatic differences here. At least no studies have found glutamine supplements to be detrimental for physical performance.

Safety

There are no established safe upper levels for supplemental glutamine. An average mixed diet will give you anywhere from 3 to 6 grams of glutamine per day. These numbers are based on a protein intake of 1.6 grams of protein per kilogram of bodyweight and day. At the same time, numerous athletes and bodybuilders consume 40 grams or more of glutamine per day in the form of supplements.

Short term studies do not indicate any negative effects from 20–30 grams of glutamine per day in healthy individuals. Unfortunately, there are no long term studies confirming that intakes like these are safe in the long run. Doses up to 0.65 grams of glutamine per kilogram of bodyweight and day do not have any negative effect in clinical settings.32

Researchers speculate if very large intakes of glutamine over a long period of time might disrupt the transfer of other amino acids to different tissues. This might create an imbalance in plasma amino acids or even increase the risk of cancer.33

Note that these are not effects shown in any clinical study, merely speculation. However, there are glutamine turnover mechanisms which could, in theory, increase the risk of negative health effects. Current research has not established that large intakes of glutamine over long periods of time is absolutely safe.

An intake of 14 grams per day seems to be safe and harmless for healthy individuals.34

That is currently the closest we have to an upper limit recommendation. Many people take a lot more glutamine than that every day, and have done so for extended periods of time, without any apparent ill effects. However, the precautionary principle and the lack of long term research prevents us from making any definitive statements about the safety of higher intakes.

Dosage

Most glutamine manufacturers recommend that you take around 5 grams of glutamine 1 to 4 times daily, in between meals. There is no scientific support for any superiority of this kind of supplementation protocol, but it seems to be industry standard.

Optimal dosage to induce muscle growth is unknown, probably because glutamine simply doesn’t seem to affect muscle growth. A number of studies have used glutamine dosages well in excess of these, without any effects on muscle mass or muscle hypertrophy.

Due to the lack of scientific evidence contraindicating the label recommendations, we can’t see any reason to suggest any other dosage protocols.

Summary and Conclusions

  • Glutamine is the most abundant amino acid in your muscles. While this makes it sound as if glutamine would be crucial to muscle growth, this does not seem to be the case. Since your body can produce the glutamine it needs, when it needs it, there is no need to supplement. If you do use a glutamine supplement, nothing special happens in this regard.
  • Glutamine does not seem to improve body composition or increase muscle mass in athletes.
  • Supplementing with glutamine does not improve the immune function in athletes. It will likely not prevent you from catching a cold during periods of intense training.
  • Glutamine does nothing to improve endurance and maximal oxygen uptake. For aerobic and endurance training purposes, glutamine is a waste of money.
  • Glutamine might benefit strength and power. If that is the case, we are mostly talking about improved recovery of strength and indices of power after a workout, not increased maximum strength. There is not enough data to say anything for sure, though. Current research is a bit all over the place, with some studies showing an effect and others not.
  • If you are healthy, your body can produce the glutamine it needs on its own. There is no scientific support for claims that glutamine supplementation can increase muscle mass, improve immune function, or increase performance.

All in all, don’t expect glutamine to improve your training results in any noticeable way. Even if the effects of glutamine supplementation are modest at best, there have been no reported side effects.


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References

  1. Is Glutamine a Conditionally Essential Amino Acid? Nutrition Reviews, Volume 48, Issue 8, August 1990, Pages 297–309.
  2. Glutamine supplementation. Annals of Intensive Care volume 1, Article number: 25 (2011).
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  4. The Journal of Nutrition, Volume 131, Issue 9, September 2001, Pages 2515S–2522S. Why Is L-Glutamine Metabolism Important to Cells of the Immune System in Health, Postinjury, Surgery or Infection?
  5. The Journal of Nutrition, Volume 138, Issue 10, October 2008, Pages 2040S–2044S. Clinical Use of Glutamine Supplementation.
  6. JPEN J Parenter Enteral Nutr. 1990 Jul-Aug;14(4 Suppl):63S-67S. Properties of glutamine release from muscle and its importance for the immune system.
  7. Nutrients 2018, 10(11), 1564. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation.
  8. The Journal of Nutritional Biochemistry, Volume 10, Issue 2, February 1999, Pages 89-95. Nonessential amino acids are not necessary to stimulate net muscle protein synthesis in healthy volunteers.
  9. The Journal of Nutritional Biochemistry, Volume 10, Issue 2, February 1999, Pages 89-95. Nonessential amino acids are not necessary to stimulate net muscle protein synthesis in healthy volunteers.
  10. European Journal of Applied Physiology, December 2001, Volume 86, Issue 2, pp 142–149. Effect of glutamine supplementation combined with resistance training in young adults.
  11. J Sports Sci Med. 2003 Dec; 2(4): 163–168. Glutamine Supplementation did not Benefit Athletes During Short-Term Weight Reduction.
  12. J Human Sport and Exercise, Vol 7, No 2. The effects of glutamine supplementation on performance and hormonal responses in non-athlete male students during eight week resistance training.
  13. Journal of Physical Education and Sport 11(3):313-316 · September 2011. Effect consumption of glutamine supplement on aerobic power, anaerobic power and body composition of soccer player.
  14. Clin Nutr. 2019 Jun;38(3):1076-1091. The effect of glutamine supplementation on athletic performance, body composition, and immune function: A systematic review and a meta-analysis of clinical trials.
  15. Medicine & Science in Sports & Exercise. 30(6):856-862, June 1998. Effect of glutamine supplementation on changes in the immune system induced by repeated exercise.
  16. Am J Physiol Cell Physiol. 2001 Oct;281(4):C1259-65. Effect of glutamine supplementation on exercise-induced changes in lymphocyte function.
  17. J Appl Physiol (1985). 2001 Aug;91(2):832-8. Effect of glutamine and protein supplementation on exercise-induced decreases in salivary IgA.
  18. Int J Sport Nutr Exerc Metab. 2000 Mar;10(1):39-50. Effect of oral glutamine supplementation on human neutrophil lipopolysaccharide-stimulated degranulation following prolonged exercise.
  19. Nutrition, Volume 13, Issues 7–8, July–August 1997, Pages 738-742. The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise.
  20. Clin Nutr. 2019 Jun;38(3):1076-1091. The effect of glutamine supplementation on athletic performance, body composition, and immune function: A systematic review and a meta-analysis of clinical trials.
  21. Clin Nutr. 2019 Jun;38(3):1076-1091. The effect of glutamine supplementation on athletic performance, body composition, and immune function: A systematic review and a meta-analysis of clinical trials.
  22. Journal of Exercise Science & Fitness, Volume 9, Issue 2, December 2011, Pages 116-122. Glutamine Supplementation in Recovery From Eccentric Exercise Attenuates Strength Loss and Muscle Soreness.
  23. Int J Sport Nutr Exerc Metab. 2015 Oct;25(5):417-26. The Influence of Oral L-Glutamine Supplementation on Muscle Strength Recovery and Soreness Following Unilateral Knee Extension Eccentric Exercise.
  24. Current Topics in Nutraceutical Research 11(1):55-62 · February 2013. L-glutamine supplementation: Effects on endurance, power and recovery.
  25. Asian J Sports Med. 2013 Jun; 4(2): 131–136. Effect of Glutamine and Maltodextrin Acute Supplementation on Anaerobic Power.
  26. J Int Soc Sports Nutr. 2012; 9: 4. L-alanyl-L-glutamine ingestion maintains performance during a competitive basketball game.
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  30. Applied Physiology, Nutrition, and Metabolism, 2006, 31(5): 518-529. Addition of glutamine to essential amino acids and carbohydrate does not enhance anabolism in young human males following exercise.
  31. European Journal of Applied Physiology, July 2012, Volume 112, Issue 7, pp 2443–2453. L-Arginine but not L-glutamine likely increases exogenous carbohydrate oxidation during endurance exercise.
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  33. JPEN J Parenter Enteral Nutr. 2013 Sep;37(5):607-16. Side effects of long-term glutamine supplementation.
  34. Regulatory Toxicology and Pharmacology, Volume 50, Issue 3, April 2008, Pages 376-399. Risk assessment for the amino acids taurine, l-glutamine and l-arginine.

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