Revisiting Glutamine

By: Jose Antonio, PHD

I wrote about glutamine way back when Bill Clinton was the president of the U.S. of A.1 Yep, while he and Monica were sharing the secrets of the old Cold War,¹ I was slaving away trying to figure out what the heck glutamine could do for you! Back then, I was of the mind that although there was a lot of clinical evidence supporting the need for supplemental glutamine in the maintenance of muscle protein mass and immune system function in critically ill patients, little work had been done that looked at its role vis-à-vis heavy exercise training. I speculated that glutamine has potential usefulness as a dietary supplement for reasons primarily related to the immune system.

Clearly, glutamine is an important amino acid. It is the most abundant free amino acid in the body. Its primary source is skeletal muscle; from there it is released into the bloodstream and transported to a variety of tissues. In fact, several studies have shown that glutamine is important for rat and human neutrophil (a type of white blood cell) function and that these cells utilize glutamine at high rates. Physical exercise has also been shown to induce considerable changes in neutrophil metabolism and function. Because neutrophils represent 50-60 percent of the total circulating leukocyte or white blood cell population and play a key role in inflammation, both physical exercise and glutamine might be expected to regulate the inflammatory process.

Now, let me get to the punchline first. If you’re like those middle-aged men in Florida who take a leisurely stroll around their gated communities three times a week for 30 minutes, taking glutamine would be about as useful as a raincoat in the Sahara desert. But if you¹re someone who busts your butt training like a maniac, whether it’s lifting weights five times a week with some cardio mixed in, or if you are a serious endurance runner doing 60 miles a week of roadwork, then glutamine just might be something worth adding to your supplement arsenal.

Protect Those White Blood Cells

If you remember way back to your biology class, you have two main types of cells in your blood, red blood cells (RBCs) and white blood cells (WBCs). Your RBCs deliver oxygen to your cells while also taking away carbon dioxide. Your WBCs (of which there are several types) help protect your body from foreign invaders; they are an integral part of your immune system. In fact, we know that lymphocytes and neutrophils can die¹ as a result of exercise. So what happens if you supplement exercise with hydrolyzed whey protein, enriched with a glutamine dipeptide (Gln)?

Here’s what happened in a group of serious athletes. Nine triathletes performed two exhaustive exercise trials with a one-week interval in between. Thirty minutes before exhaustive treadmill exercise, each subject ingested 50 grams of maltodextrin (placebo) or 50 grams of maltodextrin plus four tablets of 700 mg of hydrolyzed whey protein, enriched with 175 mg of glutamine dipeptide, dissolved in 250 mL water. What did researchers discover? Supplementation of maltodextrin plus Gln prevented the loss of lymphocyte membrane integrity and the mitochondrial membrane depolarization induced by exercise. In other words, it helped maintain the health of white blood cells.3 Keep in mind again that this is exhaustive exercise— the key word being exhaustive.¹

Lessens Risk of Illness

Perhaps the classic studies regarding glutamine that are cited most often are those published in the Nutrition journal and the European Journal of Applied Physiology. The effects of feeding glutamine were investigated both at rest in sedentary controls and after exhaustive exercise in middle-distance, marathon and ultra-marathon runners and elite rowers, in training and competition. As you will see, researchers are looking at its role in those who exercise long and hard!

Questionnaires established the incidence of infection for seven days after exercise. Here is what researchers discovered: infection levels were highest in marathon and ultra-marathon runners and in elite male rowers after intensive training. Plasma glutamine levels were decreased by approximately 20 percent, 1 hour after marathon running. A marked increase in numbers of white blood cells occurred immediately after exhaustive exercise, followed by a decrease in the numbers of lymphocytes. And giving them glutamine after exercise appeared to have a beneficial effect on the level of subsequent infections.

Specifically, athletes participating in different types of exercise consumed two drinks, containing either glutamine or placebo immediately after and 2 hours after exercise. The percentage of athletes reporting no infections was considerably higher in the glutamine group (81 percent) than in the placebo group (49 percent).5 Another area where glutamine could help is in reducing blood ammonia. Ammonia was linked to the development of fatigue as early as 1922. Also, increases in blood ammonia levels have been reported in rats after swimming and in humans after arm work, maximal cycle ergometry and treadmill exercise.6 Thus, a group of scientists examined the effect of glutamine and/or carbohydrate supplementation on ammonemia in high-level runners.

Fifteen men in pre-competitive training ran 120 minutes (approximately 21 miles) outdoors on four occasions. During the control trial, ammonia increased progressively to approximately 70 percent above rest concentration. However, supplementation with glutamine in these high-level, endurance athletes reduced the accumulation of blood ammonia.

Promotes Glycogen Repletion

One of the lesser-known effects of glutamine is its role in glycogen repletion. In this study, volunteers completed a glycogen-depleting exercise protocol. Again, you’ll notice that this is hard exercise, not a walk around the park! After the exercise bout, the subjects consumed 330 ml of one of three drinks— a glucose polymer solution, 8 grams glutamine in 330 ml glucose polymer solution, or 8 grams glutamine in 330 ml placebo. They found that glutamine alone promoted storage of muscle glycogen to an extent similar to oral glucose polymer. Ingestion of glutamine and glucose polymer together promoted the storage of carbohydrate outside of skeletal muscle, the most feasible site being the liver.8 Very interesting indeed. So you have glutamine lessening the risk of illness, decreasing levels of ammonia, protecting white blood cells, and promoting muscle glycogen repletion.

How Much Should I Take?

Acute intakes of glutamine of approximately 20-30 grams are safe in healthy, adult humans and no harm was reported in one study in which athletes consumed 28 grams of glutamine every day for 14 days. Also, doses of up to 0.65 grams/kg body mass of glutamine (in solution or as a suspension) have been reported to be tolerated by patients and did not result in abnormal plasma ammonia levels.9 Remember the Antonio adage, If it helps or has a neutral effect, try it.

With glutamine, it is clear that taking it could help you. And there’s no harm or risk in trying it. If you look at the totality of scientific evidence, it is evident that glutamine doesn¹t help everybody. But if you work your tail off, and you need that extra immune boost, then add 5-15 grams of glutamine to your post-workout shake!

Jose Antonio, PhD, is vice president of the National Strength and Conditioning Association. He has a PhD in muscle physiology and is chief executive of the International Society of Sports Nutrition.


1. Antonio J, Street C. Glutamine: a potentially useful supplement for athletes. Can J Appl Physiol, Feb 1999;24(1):1-14.

2. Lagranha CJ, Levada-Pires AC, Sellitti DF, Procopio J, Curi R, Pithon-Curi TC. The effect of glutamine supplementation and physical exercise on neutrophil function. Amino Acids, Apr 2008;34(3):337-346.

3. Cury-Boaventura MF, Levada-Pires AC, Folador A, et al. Effects of exercise on leukocyte death: prevention by hydrolyzed whey protein enriched with glutamine dipeptide. Eur J Appl Physiol, Jun 2008;103(3):289-294.

4. Castell LM, Newsholme EA. The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise. Nutrition, Jul-Aug 1997;13(7-8):738-742.

5. 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):488-490.

6. Mutch BJ, Banister EW. Ammonia metabolism in exercise and fatigue: a review. Med Sci Sports Exerc, 1983;15(1):41-50.

7. Carvalho-Peixoto J, Alves RC, Cameron LC. Glutamine and carbohydrate supplements reduce ammonemia increase during endurance field exercise. Appl Physiol Nutr Metab, Dec 2007;32(6):1186-1190.

8. 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, Jun 1999;86(6):1770-1777.

9. Gleeson M. Dosing and efficacy of glutamine supplementation in human exercise and sport training. J Nutr, Oct 2008;138(10):2045S-2049S.


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