What is glutamine as a therapeutic supplement?

Overview

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 of 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.

Requirements and 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 grams (g).

Therapeutic Dosages

Typical therapeutic dosages of glutamine used in studies ranged 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.

Another small double-blind, placebo-controlled trial suggests that glutamine
might support standard therapy for angina. Angina is too dangerous a
disease for self-treatment. A person who has angina should 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 human immunodeficiency virus, or HIV), digestive distress caused by cancer chemotherapy, and symptoms of inflammatory bowel disease.

Glutamine appears to help reduce leakage through the intestinal wall. 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, there is no reliable evidence that glutamine actually provides any benefits for food allergies.

Preliminary evidence suggests that glutamine combined with antioxidants
or other nutrients may help people with HIV to gain weight. 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.

Glutamine has been tried as an ergogenic aid for bodybuilders, but two small trials failed to find any evidence of benefit. 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 and ulcers, and as a “ brain booster.” However, there is little to no scientific evidence for any of these uses.

Scientific Evidence

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.

A double-blind, placebo-controlled study evaluated the benefits of supplemental glutamine (5 g) taken at the end of exercise in 151 endurance athletes. The results showed a significant decrease in infections among treated athletes. Only 19 percent of the athletes taking glutamine got sick, compared with 51 percent of those on a placebo.

Recovery from critical illness. One small double-blind study found that glutamine supplements might have significant nutritional benefits for seriously ill people. In this study, eighty-four 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 six months, fourteen of the forty-two patients receiving glutamine had died, compared with twenty-four 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.

HIV support. One double-blind, placebo-controlled study of
twenty-five people found that use of glutamine at 30 g daily for seven days
reduced diarrhea caused by the protease inhibitor nelfinavir. 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. 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.

Cancer chemotherapy. There is mixed evidence regarding whether
glutamine can reduce the side effects of cancer chemotherapy.
A double-blind, placebo-controlled trial of seventy 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. However, a double-blind trial of sixty-five women undergoing
various forms of chemotherapy for advanced breast cancer failed to find glutamine
at 30 g per day helpful for reducing diarrhea. 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.

Angina. Researchers conducted investigations in rats and found that glutamine could protect the heart from damage caused by loss of oxygen. 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 forty 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. However, two
double-blind trials enrolling a total of thirty people found no benefit.

Sports performance. A double-blind, placebo-controlled trial of thirty-one people ranging from eighteen to twenty-four years of age evaluated the potential benefits of glutamine as a sports supplement for improving response to resistance training (weight lifting). Participants received either a placebo or glutamine at a dose of 0.9 g per kg of lean tissue mass. After six 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.

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.

Nevertheless, those who are hypersensitive to monosodium glutamate
(MSG) should use glutamine with caution, as the body
metabolizes glutamine into glutamate. In addition, because many antiepilepsy 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. In a small randomized trial including thirty 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. Maximum safe dosages for young
children, pregnant or nursing women, and those with severe liver or kidney disease
have not been determined.

Important Interactions

Persons taking antiseizure medications, including carbamazepine, phenobarbital,
phenytoin (Dilantin), primidone (Mysoline), and valproic acid (Depakene), should
use glutamine only under medical supervision. Persons taking nelfinavir or other
protease
inhibitors for HIV, or cancer chemotherapy drugs should note
that concurrent glutamine may reduce intestinal side effects.

Bibliography

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Antonio, J., et al. “The Effects of High-Dose Glutamine Ingestion on Weightlifting Performance.” Journal of Strength and Conditioning Research 16 (2002): 157-160.

Candow, D. G., et al. “Effect of Glutamine Supplementation Combined with Resistance Training in Young Adults.” European Journal of Applied Physiology 86 (2001): 142-149.

Clark, R. H., et al. “Nutritional Treatment for Acquired Immunodeficiency Virus-Associated Wasting Using Beta-Hydroxy Beta-Methylbutyrate, Glutamine, and Arginine.” JPEN: Journal of Parenteral and Enteral Nutrition 24 (2000): 133-139.

Daniele, B., et al. “Oral Glutamine in the Prevention of Fluorouracil-Induced Intestinal Toxicity.” Gut 48 (2001): 28-33.

Galera, S. C., et al. “The Safety of Oral Use of L-Glutamine in Middle-Aged and Elderly Individuals.” Nutrition 26, no. 4 (2010): 375-381.

Khogali, S. E., et al. “Is Glutamine Beneficial in Ischemic Heart Disease?” Nutrition 18 (2002): 123-126.

Quan, Z. F., et al. “Effect of Glutamine on Change in Early Postoperative Intestinal Permeability and Its Relation to Systemic Inflammatory Response.” World Journal of Gastroenterology 10 (2004): 1992-1994.

Shao, A., and J. N. Hathcock. “Risk Assessment for the Amino Acids Taurine, L-Glutamine, and L-Arginine.” Regulatory Toxicology and Pharmacology 50, no. 3 (2008): 376-399.