L-Glutamine

Overview

L-glutamine is the most prevalent amino acid in the blood, accounting for 30-35 percent of the amino acid nitrogen in the plasma. Because L-glutamine contains two ammonia groups, one from its precursor, glutamate, and the other from free ammonia in the bloodstream, one of L-glutamine's roles is as a "nitrogen shuttle," helping to protect the body from high levels of ammonia.

Human cells readily synthesize L-glutamine via the enzyme L-glutamine synthetase, which is found in high concentration in skeletal muscle, liver, brain, and stomach tissue. Because of the body's capacity to synthesize this amino acid, and because of the relative amount of L-glutamine in the body compared to other amino acids, it has long been thought that L-glutamine was not a necessary component of the diet. In fact, approximately 5 - 10 grams per day of L-glutamine is consumed in the diet. Under normal circumstances, dietary intake and synthesis of L-glutamine is adequate and balanced with demand. (1) In situations where a particular tissue is in greater need of L-glutamine, inter-organ transfer of L-glutamine usually makes up for increased site-specific requirements. However, under certain pathological circumstances, the body's tissues need more L-glutamine than the overall amount supplied by diet and de novo synthesis. During catabolic stress, for instance, intracellular L-glutamine levels can drop more than 50 percent, and plasma concentration can fall 30 percent. (2) It is under these and other circumstances that supplemental L-glutamine becomes necessary.

L-glutamine can be converted to other amino acids, to glucose in the liver, and contributes to nucleotide, amino sugar, and protein biosynthesis. L-glutamine is one of three amino acids involved in glutathione synthesis. Glutathione, an intracellular antioxidant and hepatic detoxifier, is comprised of glutamic acid, cysteine, and glycine. (3)

Dosage Info

Dosage Range

500-4,000mg, 3 times daily.

Oral rinse: 16gm in 240ml normal saline, swish and expectorate, 4 times a day (for radiation therapy-induced mucositis and chemotherapy-induced stomatitis).

Most Common Dosage

500-1,000mg, 3 times daily.

Dosage Forms

Powder, capsules, tablets, and liquid.

Adult RDI

None established

Adult ODA

None established

Active Forms

L-glutamine.

Absorption

L-glutamine is readily absorbed from the intestinal tract.

Toxicities & Precautions

General

L-glutamine is generally considered to be safe in recommended dosages.

Side Effects

L-glutamine may cause diarrhea in a small percentage of people. If this occurs, a dose reduction may be required or the use of L-glutamine discontinued.

Functions in the Body

Non-essential amino acid

Human cells can readily synthesize it via activity of the enzyme L-glutamine synthetase, which is found in high concentration in skeletal muscle, liver, brain, and stomach tissue. (4) Because of the body's capacity to synthesize this amino acid, and because of the relative amount of L-glutamine in the body compared to other amino acids, it has long been thought that L-glutamine was not a necessary component of the diet.

Cellular energy, growth and repair

In times of metabolic stress, L-glutamine (non-essential amino acid) is released into circulation, where it is transported to the tissue in need. (5)

DNA synthesis

Aids in induction of mRNA and DNA. (6)

Immune support

Reported to increase immune function via increased NK cell activity or neutrophil activation; increased macrophage activity. (7) Aids in decreasing intestinal permeability, thereby affecting immune system health. (8)

Clinical Applications

Intestinal Health

The gastrointestinal tract is by far the largest user of L-glutamine in the body. The small intestine accounts for the largest uptake of L-glutamine of any organ, absorbing this amino acid from the lumen of the gut as well as from the bloodstream. Epithelial cells that line the small intestine (termed enterocytes) use L-glutamine as their principal metabolic fuel, eventually converting it to ATP and energy. (9) Since enterocytes have little L-glutamine synthesizing activity and contain a great amount of glutaminase (metabolizes L-glutamine), these cells of the gastrointestinal tract are very dependent on a constant supply of L-glutamine.

The gastrointestinal tract is continuously exposed to the exterior environment of the body via food, liquid, and swallowed salivary and mucus secretions, and therefore contains a large number of immune cells along its length. L-glutamine's positive effects on the GI tract appear to stem from its ability to "feed" immune cells as well as mucosal cells. (10) A decrease in L-glutamine can result in atrophy of the gut mucosa, decreased gut-associated lymphoid tissue (GALT), and increased intestinal permeability. (11) Injury of any tissue excluding the intestines shunts L-glutamine away from the blood and into these tissues, making less L-glutamine available for the intestines. As L-glutamine is depleted, wound healing is impaired, intestinal permeability increases, and the risk of microbial translocation, sepsis, and multiple organ failure increases significantly. (12) Intestinal permeability can be caused by a variety of factors, including trauma (surgical, burns, others), (13) antibiotic use, (14) and some common food allergies such as cow’s milk (15) and gluten (wheat) sensitivity.

It has been reported that intestinal mucosal cellular levels of L-glutamine are decreased in problems associated with the GIT, including ulcerative colitis, IBS, and Crohn’s Disease. (16) L-glutamine has been reported effective in these problems associated with the GIT. (17) , (18) Although current studies with L-glutamine in the treatment of ulcers are lacking, an older double-blind study reported that 22 of 24 ulcer patients treated with L-glutamine, 400mg, four times daily, exhibited complete healing within four weeks, which was documented and verified with x-rays.

Cortisol Induced Protein Catabolism

L-glutamine has been reported to block catabolism of muscle tissue in elevated cortisol states. This could provide benefits in tissue wasting or catabolic phenomena in addition to finding value in managing the metabolic effects of stress. (19)

Liver Protection

Supplemental L-glutamine can support hepatic glutathione levels, which help protect the liver and enhance hepatic detoxification. (20)

Athletic Performance

Plasma L-glutamine levels have been found to be decreased in endurance athletes who train too often and at such high intensity that muscles do not fully recover between workouts. (21) , (22) These athletes tend to have a higher incidence of infectious diseases and allergies, and have been noted to have swollen lymph nodes and experience slower wound healing. (23) They also have reduced markers of immune function compared to athletes not over-training. (24) It has been suggested that decreased plasma L-glutamine may stem from a loss of L-glutamine stores from skeletal muscle while exercising, which are not given the chance to rebuild before the next workout. This may reduce the long-term availability of L-glutamine for immune cells and fibroblasts. Low-intensity exercise does not seem to be associated with L-glutamine depletion from skeletal muscle or a deleterious effect on the immune system. (25) Athletes undergoing a strenuous workout schedule may be able to reduce the risk of infections by supplementing with L-glutamine. (26) , (27) In a study supplementing creatine monohydrate and glutamine, athletes experienced a significant increase in their body mass, lean body mass, and initial rate of power production during multiple cycle ergometer bouts. (28)

Growth Hormone Secretagogue

L-glutamine in doses of two grams taken at one time can stimulate the release of growth hormone, which may partly be responsible for its anabolic effects. (29)

Alcoholism

Changes or imbalances in plasma amino acid patterns during withdrawal from ethanol has been reported in clinical studies. (30) L-glutamine, along with riboflavin, has been reported effective in relieving symptoms of alcoholism, including termination and treatment of abstinence. (31)

In alcoholics, enzymatic and non-enzymatic mixed-function oxidase systems have been reported to generate an oxidant that catalyzes the inactivation of L-glutamine synthetase, with subsequent decreasing of L-glutamine levels. (32) Through its inhibitory effect on L-glutamine synthetase activity and resulting excitotoxicity of the CNS, alcohol may contribute to neuronal death and possibly to dependence on alcohol. (33)

Cancer

One area of L-glutamine research that has recently gained attention is the effect of L-glutamine on cancer therapy regimens. Interestingly, L-glutamine is the main fuel for most rapidly growing tumors, which have high glutaminase activity, similar to small intestine enterocytes. (34) Tumor growth can deplete skeletal muscle L-glutamine, providing less fuel for enterocytes and creating a catabolic state. It is suggested the tumor can become a "glutamine trap," further enhancing systemic L-glutamine loss. (35) Researchers investigated the consumption of L-glutamine by colonic tumors and noted these tumors did not extract L-glutamine at a greater rate than normal intestinal tissue, regardless of the tumor size, type, differentiation, classification, or vascularization. (36) Regardless of the speed of uptake, the mass of the tumor could potentially rob L-glutamine from all healthy tissue.

There has been some concern about supplementing cancer patients with L-glutamine. It was thought that supplementation may increase tumor growth. In vitro cell culture studies report a dependence on L-glutamine and increased cellular growth with the addition of L-glutamine. (37) , (38) In vivo data has been reported to be the opposite. (39) , (40) In fact, an animal study demonstrated the opposite finding that L-glutamine supplementation reduced tumor growth. (41) In this study, tumor growth was reduced by 40 percent, and a 30 percent increase in NK activity was noted as well. The authors concluded that support of host L-glutamine stores may improve immunity, specifically NK cell activity, thereby potentially decreasing tumor growth.

Laboratory studies have been conducted utilizing L-glutamine in conjunction with radiation and chemotherapy, with promising results. (42) , (43) One study reported oral L-glutamine significantly reduced the duration and severity of radiation-induced oral mucositis in the radiotherapy of head and neck cancer. (44) A slurry of 16 gm of L-glutamine in 240ml of normal saline four times a day was used as an oral rinse for patients. Oral L-glutamine has also been administered to patients with chemotherapy induced stomatitis, with a significant reduction in oral pain and mucosal inflammation. (45) , (46) However, one study reported the use of oral L-glutamine in a preparatory regimen to decrease GI toxicity of chemotherapy and radiation associated with bone marrow transplant. (47) GI structure and function were not improved, as determined by the number of days required until oral intake resumed, length of hospitalization, number of days and highest grade of mucositis, and quantity and number of days of diarrhea.

Improves Immune Function

A laboratory study reported that increased L-glutamine in the diet enhanced the ability of macrophages to respond to stimulation in terms of cytokine production. (48) These observations suggest that increasing the availability of L-glutamine orally could promote immune responses involving macrophage-derived cytokines. L-glutamine also aids in increasing immune health by decreasing intestinal permeability. Lymphocytes respond to L-glutamine supplementation by proliferating, as well as producing, more lymphocyte-derived cytokines in vitro. (49) NK cell activity has also been reported to be increased with L-glutamine use. (50)

Wound Healing

Fibroblasts, lymphocytes, and macrophages use L-glutamine as a metabolic fuel, as well as using it for nucleotide synthesis, which regulates cellular proliferation. L-glutamine depletion can slow fibroblast growth, while adequate L-glutamine can stimulate growth and cellular proliferation in vitro. The dependence on L-glutamine in fibroblasts makes this nutrient a component of the healing response in wounds. (51) Wounds such as burns, surgical and traumatic wounds, cuts, and others may heal faster with the supplementation of L-glutamine. (52) , (53)

Symptoms and Causes of Deficiency

L-glutamine is not an essential nutrient for humans, and a deficiency condition has not been identified. However, it is considered conditionally essential in a variety of pathologic conditions.

Dietary Sources

L-glutamine can be found in beans, brewer's yeast, brown rice bran, caseinate, dairy products, eggs, fish, lactalbumin, legumes, meat, nuts, seafood, seeds, soy, whey, whole grains, hydrolysis of gluten, beet root, or other proteins.

References

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