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Glutamine
Glutamine, or L-glutamine, is an amino acid derived from another amino acid, glutamic acid. Glutamine plays a role in the health of the immune system, digestive tract, and muscle cells, as well as other bodily functions. It appears to serve as a fuel for the cells that line the intestines. Heavy exercise, infection, surgery, and trauma can deplete the body's glutamine reserves, particularly in muscle cells.
The fact that glutamine does so many good things in the body has led people to try glutamine supplements as a treatment for various conditions, including preventing the infections that often follow endurance exercise, reducing symptoms of overtraining syndrome, improving nutrition in critical illness, alleviating allergies, and treating digestive problems.
Sources
There is no daily requirement for glutamine because the body can make its own supply. As mentioned earlier, various severe stresses may result in a temporary glutamine deficiency.
High-protein foods such as meat, fish, beans, and dairy products are excellent sources of glutamine. Typical daily intake from food ranges from approximately 1 to 6 g.
Therapeutic Dosages
Typical therapeutic dosages of glutamine used in studies ranges from 3 to 30 g daily, divided into several separate doses.
Therapeutic Uses
Endurance athletes frequently catch
cold
after completing a marathon or similar forms of exercise. Preliminary evidence, including one small
double-blind, placebo-controlled
trial, suggests that glutamine supplements might help prevent such infections.
1-5
Another small double-blind, placebo-controlled trial suggests that glutamine might support standard therapy for
angina
.
34Note
: Angina is too dangerous a disease for self-treatment. If you have angina, do not take glutamine (or any other supplement) except on the advice of a physician.
Because, as noted above, cells of the intestine use glutamine for fuel, the supplement has been tried as a supportive treatment for various digestive conditions, with mixed results. Tested uses include reducing diarrhea caused by the drug
nelfinavir
(used for treatment of
HIV
),
37
digestive distress caused by
cancer chemotherapy
,
15,16
and symptoms of
inflammatory bowel disease
.
9-14
Glutamine appears to help reduce leakage through the intestinal wall.
7,8,38
On this basis, glutamine has also been suggested as a treatment for
food allergies
, according to the idea that in some people whole proteins leak through the wall of the digestive tract and enter the blood, causing allergic reactions (so-called leaky gut syndrome). However, as yet there is no reliable evidence that glutamine actually provides any benefits for food allergies.
Preliminary evidence suggests glutamine combined with
antioxidants
or other nutrients may help people with
HIV
to
gain weight
.
17,18
Glutamine (often combined with other nutrients) also appears to be useful as a nutritional supplement for people undergoing recovery from
major surgery
or critical illness.
6,39
Glutamine has been tried as an
ergogenic aid
for bodybuilders, but two small trials failed to find any evidence of benefit.
35,36
Based on glutamine's role in muscle, it has been suggested that glutamine might be useful for athletes experiencing
overtraining syndrome
. As the name suggests, this syndrome is the cumulative effect of a training regimen that allows too little rest and recovery between workouts. Symptoms include depression, fatigue, reduced performance, and physiological signs of stress. Glutamine supplements have additionally been proposed as treatment for
attention deficit disorder
,
ulcers
, and as a "
brain booster
." However, there is little to no scientific evidence for any of these uses.
What Is the Scientific Evidence for Glutamine?
Infections in Athletes
Endurance exercise temporarily reduces
immunity
to infection. This effect may be due in part to reduction of glutamine in the body, although not all studies agree.
19-23,34
A double-blind, placebo-controlled study evaluated the benefits of supplemental glutamine (5 g) taken at the end of exercise in 151 endurance athletes.
24
The results showed a significant decrease in infections among treated athletes. Only 19% of the athletes taking glutamine got sick, as compared to 51% of those on placebo.
For other approaches to this problem, see the article titled
Sports and Fitness Support: Aids to Recovery
.
Recovery From Critical Illness
One small double-blind study found that glutamine supplements might have significant nutritional benefits for seriously ill people.
25
In this study, 84 critically ill hospital patients were divided into two groups. All the patients were being fed through a feeding tube. One group received a normal feeding-tube diet, whereas the other group received this diet plus supplemental glutamine. After 6 months, 14 of the 42 patients receiving glutamine had died, compared with 24 of the control group. The glutamine group also left both the intensive care ward and the hospital significantly sooner than the patients who did not receive glutamine. Benefits have been seen in other controlled trials as well.
40
HIV Support
One double-blind, placebo-controlled study of 25 people found that use of glutamine at 30 g daily for 7 days reduced diarrhea caused by the protease inhibitor nelfinavir.
41
In addition, combination supplements containing glutamine may help reverse HIV-related weight loss. For example, a double-blind, placebo-controlled study found that a combination of glutamine and
antioxidants
(vitamins
C
and
E
,
beta-carotene
,
selenium
, and
N-acetyl cysteine
) led to significant weight gain in people with
HIV
who had lost weight.
26
Another small double-blind trial found that combination treatment with glutamine,
arginine
, and
beta-hydroxy beta-methylbutyrate
(HMB) could increase muscle mass and possibly improve immune status.
27
Cancer Chemotherapy
There is mixed evidence regarding whether glutamine can reduce the side effects of
cancer chemotherapy
. A double-blind, placebo-controlled trial of 70 people undergoing chemotherapy with the drug 5-FU for colorectal cancer found that glutamine at a dose of 18 g daily improved intestinal function and structure, and reduced the need for antidiarrheal drugs.
28
However, a double-blind trial of 65 women undergoing various forms of chemotherapy for advanced breast cancer failed to find glutamine at 30 g per day helpful for reducing diarrhea.
29
Based on a review of several studies, there is some preliminary evidence that glutamine may help relieve the pain associated with nerve damage (peripheral neuropathy) caused by some chemotherapy drugs.
43
Angina
Researchers conducted investigations in rats and found that glutamine could protect the heart from damage caused by loss of oxygen.
34
Based on these findings, they went on to evaluate the effects of glutamine in ten people with chronic
angina
who were also taking standard medication. In this double-blind, placebo-controlled trial, each participant received a single oral dose of glutamine (80 mg per kg of body weight) or placebo 40 minutes before a treadmill test. A week later, each participant received the opposite treatment.
The results showed that use of glutamine significantly enhanced the ability of participants to exercise without showing signs of heart stress. Based on the results in rats, researchers suggest that a higher dose of glutamine would be worth trying.
Crohn's Disease
Because glutamine is the major fuel source for cells of the small intestine, glutamine has been proposed as a treatment for
Crohn's disease
, a disease of the small intestine.
30
However, two double-blind trials enrolling a total of 30 people found no benefit.
31,32
Sports Performance
A double-blind, placebo-controlled trial of 31 people ranging from 18 to 24 years of age evaluated the potential benefits of glutamine as a
sports supplement
for improving response to resistance training (weight lifting).
35
Participants received either placebo or glutamine at a dose of 0.9 g per kg of lean tissue mass. After 6 weeks of resistance training, participants taking glutamine showed no relative improvement in performance, composition, or muscle protein degradation.
Similarly, negative results were seen in a small double-blind, placebo-controlled trial of weightlifters using a dose of 0.3 g per kg of total body weight.
36
Safety Issues
As a naturally occurring amino acid, glutamine is thought to be a safe supplement when taken at recommended dosages. There is strong evidence that glutamine is safe at levels up to 14 g per day, although higher dosages have been tested without apparent adverse effects.
42
Nevertheless, those who are hypersensitive to monosodium glutamate (MSG) should use glutamine with caution, as the body metabolizes glutamine into glutamate. Also, because many anti-epilepsy drugs work by blocking glutamate stimulation in the brain, high dosages of glutamine might conceivably overwhelm these drugs and pose a risk to people with
epilepsy
.
In one case report, high doses of the supplement L-glutamine (more than 2 g per day) may have triggered episodes of mania in two people not previously known to have
bipolar disorder
.
33
In a small randomized trial including 30 older people, L-glutamine did not cause any clinically significant changes in lab tests. The researchers did urge caution, though, since there were some statistically significant changes for certain kidney levels.
44
Maximum safe dosages for young children, pregnant or nursing women, or those with severe liver or kidney disease have not been determined.
Interactions You Should Know About
If you are taking:
- Antiseizure medications, including carbamazepine , phenobarbital , phenytoin (Dilantin) , primidone (Mysoline) , and valproic acid (Depakene) : Use glutamine only under medical supervision.
- Nelfinavir or other protease inhibitors for HIV, or cancer chemotherapy drugs: Use of glutamine may reduce intestinal side effects.
References
1
Castell LM, Poortmans JR, Newsholme EA. Does glutamine have a role in reducing infections in athletes? Eur J Appl Physiol Occup Physiol. 1996;73:488-490.
Castell LM, Poortmans JR, Newsholme EA. Does glutamine have a role in reducing infections in athletes? Eur J Appl Physiol Occup Physiol. 1996;73:488-490.
2
Castell LM, Newsholme EA. Glutamine and the effects of exhaustive exercise upon the immune response. Can J Physiol Pharmacol. 1998;76:524-532.
Castell LM, Newsholme EA. Glutamine and the effects of exhaustive exercise upon the immune response. Can J Physiol Pharmacol. 1998;76:524-532.
3
Rohde T, MacLean DA, Hartkopp A, et al. The immune system and serum glutamine during a triathlon. Eur J Appl Physiol . 1996;74:428-434.
Rohde T, MacLean DA, Hartkopp A, et al. The immune system and serum glutamine during a triathlon. Eur J Appl Physiol . 1996;74:428-434.
4
Rowbottom DG, Keast D, Morton AR, et al. The emerging role of glutamine as an indicator of exercise stress and overtraining. Sports Med . 1996;21:80-97.
Rowbottom DG, Keast D, Morton AR, et al. The emerging role of glutamine as an indicator of exercise stress and overtraining. Sports Med . 1996;21:80-97.
5
Castell LM, Newsholme EA. The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise. Nutrition. 1997;13:738-742.
Castell LM, Newsholme EA. The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise. Nutrition. 1997;13:738-742.
6
Griffiths RD, Jones C, Palmer TE. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition . 1997;13:295-302.
Griffiths RD, Jones C, Palmer TE. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition . 1997;13:295-302.
7
van der Hulst RR, van Kreel BK, von Meyenfeldt MF, et al. Glutamine and the preservation of gut integrity. Lancet . 1993;341:1363-1365.
van der Hulst RR, van Kreel BK, von Meyenfeldt MF, et al. Glutamine and the preservation of gut integrity. Lancet . 1993;341:1363-1365.
8
Zoli G, Care M, Falco F, et al. Effect of oral glutamine on intestinal permeability and nutritional status in Crohn's disease [abstract]. Gastroenterology . 1995;108:A766.
Zoli G, Care M, Falco F, et al. Effect of oral glutamine on intestinal permeability and nutritional status in Crohn's disease [abstract]. Gastroenterology . 1995;108:A766.
9
Alverdy JC. Effects of glutamine-supplemented diets on immunology of the gut. JPEN J Parenter Enteral Nutr .1990;14(suppl 4):109S-113S.
Alverdy JC. Effects of glutamine-supplemented diets on immunology of the gut. JPEN J Parenter Enteral Nutr .1990;14(suppl 4):109S-113S.
10
Fox AD, Kripke SA, Berman JR, et al. Reduction of the severity of enterocolitis by glutamine-supplemented enteral diets. Surg Forum . 1987;38:43-44.
Fox AD, Kripke SA, Berman JR, et al. Reduction of the severity of enterocolitis by glutamine-supplemented enteral diets. Surg Forum . 1987;38:43-44.
11
Fujita T, Sakurai K. Efficacy of glutamine-enriched enteral nutrition in an experimental model of mucosal ulcerative colitis. Br J Surg . 1995;82:749-751.
Fujita T, Sakurai K. Efficacy of glutamine-enriched enteral nutrition in an experimental model of mucosal ulcerative colitis. Br J Surg . 1995;82:749-751.
12
van der Hulst RR, van Kreel BK, von Meyenfeldt MF, et al. Glutamine and the preservation of gut integrity. Lancet . 1993;341:1363-1365.
van der Hulst RR, van Kreel BK, von Meyenfeldt MF, et al. Glutamine and the preservation of gut integrity. Lancet . 1993;341:1363-1365.
13
Akobeng AK, Miller V, Stanton J, et al. Double-blind randomized controlled trial of glutamine-enriched polymeric diet in the treatment of active Crohn's disease. J Pediatr Gastroenterol Nutr . 2000;30:78-84.
Akobeng AK, Miller V, Stanton J, et al. Double-blind randomized controlled trial of glutamine-enriched polymeric diet in the treatment of active Crohn's disease. J Pediatr Gastroenterol Nutr . 2000;30:78-84.
14
Den Hond E, Hiele M, Peeters M, et al. Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn's disease. JPEN J Parenter Enteral Nutr . 1999;23:7-11.
Den Hond E, Hiele M, Peeters M, et al. Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn's disease. JPEN J Parenter Enteral Nutr . 1999;23:7-11.
15
van der Hulst RR, van Kreel BK, von Meyenfeldt MF, et al. Glutamine and the preservation of gut integrity. Lancet .1993;341:1363-1365.
van der Hulst RR, van Kreel BK, von Meyenfeldt MF, et al. Glutamine and the preservation of gut integrity. Lancet .1993;341:1363-1365.
16
Daniele B, Perrone F, Gallo C, et al. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial. Gut. 2001;48:28-33.
Daniele B, Perrone F, Gallo C, et al. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial. Gut. 2001;48:28-33.
17
Shabert JK, Winslow C, Lacey JM, et al. Glutamine-antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial. Nutrition . 1999;15:860-864.
Shabert JK, Winslow C, Lacey JM, et al. Glutamine-antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial. Nutrition . 1999;15:860-864.
18
Clark RH, Feleke G, Din M, et al. Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study. JPEN J Parenter Enteral Nutr . 2000;24:133-139.
Clark RH, Feleke G, Din M, et al. Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study. JPEN J Parenter Enteral Nutr . 2000;24:133-139.
19
Rohde T, MacLean DA, Hartkopp A, et al. The immune system and serum glutamine during a triathlon. Eur J Appl Physiol . 1996;74:428-434.
Rohde T, MacLean DA, Hartkopp A, et al. The immune system and serum glutamine during a triathlon. Eur J Appl Physiol . 1996;74:428-434.
20
Rowbottom DG, Keast D, Morton AR. The emerging role of glutamine as an indicator of exercise stress and overtraining. Sports Med . 1996;21:80-97.
Rowbottom DG, Keast D, Morton AR. The emerging role of glutamine as an indicator of exercise stress and overtraining. Sports Med . 1996;21:80-97.
21
Castell LM, Newsholme EA. Glutamine and the effects of exhaustive exercise upon the immune response. Can J Physiol Pharmacol. 1998;76:524-532.
Castell LM, Newsholme EA. Glutamine and the effects of exhaustive exercise upon the immune response. Can J Physiol Pharmacol. 1998;76:524-532.
22
Castell LM, Newsholme EA. The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise. Nutrition. 1997;13:738-742.
Castell LM, Newsholme EA. The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise. Nutrition. 1997;13:738-742.
23
Mackinnon LT, Hooper SL. Plasma glutamine and upper respiratory tract infection during intensified training in swimmers. Med Sci Sports Exerc. 1996;28:285-290.
Mackinnon LT, Hooper SL. Plasma glutamine and upper respiratory tract infection during intensified training in swimmers. Med Sci Sports Exerc. 1996;28:285-290.
24
Castell LM, Poortmans JR, Newsholme EA. Does glutamine have a role in reducing infections in athletes? Eur J Appl Physiol Occup Physiol. 1996;73:488-490.
Castell LM, Poortmans JR, Newsholme EA. Does glutamine have a role in reducing infections in athletes? Eur J Appl Physiol Occup Physiol. 1996;73:488-490.
25
Griffiths RD, Jones C, Palmer TE. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition . 1997;13:295-302.
Griffiths RD, Jones C, Palmer TE. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition . 1997;13:295-302.
26
Shabert JK, Winslow C, Lacey JM, et al. Glutamine-antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial. Nutrition . 1999;15:860-864.
Shabert JK, Winslow C, Lacey JM, et al. Glutamine-antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial. Nutrition . 1999;15:860-864.
27
Clark RH, Feleke G, Din M, et al. Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study. JPEN J Parenter Enteral Nutr . 2000;24:133-139.
Clark RH, Feleke G, Din M, et al. Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study. JPEN J Parenter Enteral Nutr . 2000;24:133-139.
28
Daniele B, Perrone F, Gallo C, et al. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial. Gut. 2001;48:28-33.
Daniele B, Perrone F, Gallo C, et al. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial. Gut. 2001;48:28-33.
29
Bozzetti F, Biganzoli L, Gavazzi C, et al. Glutamine supplementation in cancer patients receiving chemotherapy: a double-blind randomized study. Nutrition. 1997;13:748-751.
Bozzetti F, Biganzoli L, Gavazzi C, et al. Glutamine supplementation in cancer patients receiving chemotherapy: a double-blind randomized study. Nutrition. 1997;13:748-751.
30
van der Hulst, RR, van Kreel BK, von Meyenfeldt MF, et al. Glutamine and the preservation of gut integrity. Lancet. 1993;341:1363-1365.
van der Hulst, RR, van Kreel BK, von Meyenfeldt MF, et al. Glutamine and the preservation of gut integrity. Lancet. 1993;341:1363-1365.
31
Den Hond ED, Hiele M, Peeters M, et al. Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn's disease. JPEN J Parenter Enteral Nutr. 1999;23:7-11.
Den Hond ED, Hiele M, Peeters M, et al. Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn's disease. JPEN J Parenter Enteral Nutr. 1999;23:7-11.
32
Akobeng AK, Miller V, Stanton J, et al. Double-blind randomized controlled trial of glutamine-enriched polymeric diet in the treatment of active Crohn's disease. J Pediatr Gastroenterol Nutr. 2000;30:78-84.
Akobeng AK, Miller V, Stanton J, et al. Double-blind randomized controlled trial of glutamine-enriched polymeric diet in the treatment of active Crohn's disease. J Pediatr Gastroenterol Nutr. 2000;30:78-84.
33
Mebane AH. L-Glutamine and mania [letter]. Am J Psychiatry. 1984;141:1302-1303.
Mebane AH. L-Glutamine and mania [letter]. Am J Psychiatry. 1984;141:1302-1303.
34
Khogali SE, Pringle SD, Weryk BV, et al. Is glutamine beneficial in ischemic heart disease? Nutrition. 2002;18:123-126.
Khogali SE, Pringle SD, Weryk BV, et al. Is glutamine beneficial in ischemic heart disease? Nutrition. 2002;18:123-126.
35
Candow DG, Chilibeck PD, Burke DG, et al. Effect of glutamine supplementation combined with resistance training in young adults. Eur J Appl Physiol. 2001;86:142-149.
Candow DG, Chilibeck PD, Burke DG, et al. Effect of glutamine supplementation combined with resistance training in young adults. Eur J Appl Physiol. 2001;86:142-149.
36
Antonio J, Sanders MS, Kalman D, et al. The effects of high-dose glutamine ingestion on weightlifting performance. J Strength Cond Res. 2002;16:157-160.
Antonio J, Sanders MS, Kalman D, et al. The effects of high-dose glutamine ingestion on weightlifting performance. J Strength Cond Res. 2002;16:157-160.
37
Huffman FG, Walgren ME. L-Glutamine supplementation improves nelfinavir-associated diarrhea in HIV-infected individuals. HIV Clin Trials . 2003;4:324-329.
Huffman FG, Walgren ME. L-Glutamine supplementation improves nelfinavir-associated diarrhea in HIV-infected individuals. HIV Clin Trials . 2003;4:324-329.
38
Quan ZF, Yang C, Li N, Li JS. Effect of glutamine on change in early postoperative intestinal permeability and its relation to systemic inflammatory response. World J Gastroenterol . 2004;10:1992-1994.
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39
Garcia-de-Lorenzo A, Zarazaga A, Garcia-Luna PP, et al. Clinical evidence for enteral nutritional support with glutamine: a systematic review. Nutrition . 2003;19:805-811.
Garcia-de-Lorenzo A, Zarazaga A, Garcia-Luna PP, et al. Clinical evidence for enteral nutritional support with glutamine: a systematic review. Nutrition . 2003;19:805-811.
40
Garcia-de-Lorenzo A, Zarazaga A, Garcia-Luna PP, et al. Clinical evidence for enteral nutritional support with glutamine: a systematic review. Nutrition . 2003;19:805-811.
Garcia-de-Lorenzo A, Zarazaga A, Garcia-Luna PP, et al. Clinical evidence for enteral nutritional support with glutamine: a systematic review. Nutrition . 2003;19:805-811.
41
Huffman FG, Walgren ME. L-Glutamine supplementation improves nelfinavir-associated diarrhea in HIV-infected individuals. HIV Clin Trials . 2003;4:324-329.
Huffman FG, Walgren ME. L-Glutamine supplementation improves nelfinavir-associated diarrhea in HIV-infected individuals. HIV Clin Trials . 2003;4:324-329.
42
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43
Amara S. Oral Glutamine for the prevention of chemotherapy-induced peripheral neuropathy. A nn Pharmacother. 2008 Aug 12.
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44
Galera SC, Fechine FV, Teixeira MJ, Coelho ZC, de Vasconcelos RC, de Vasconcelos PR. The safety of oral use of L-glutamine in middle-aged and elderly individuals. Nutrition. 2010;26(4):375-381.
Galera SC, Fechine FV, Teixeira MJ, Coelho ZC, de Vasconcelos RC, de Vasconcelos PR. The safety of oral use of L-glutamine in middle-aged and elderly individuals. Nutrition. 2010;26(4):375-381.
