Glutamine is the most abundant of the amino acids in the human body. Its main storage site is in the musculature, where about 60% of all the unbound amino acids are glutamine (glutamine makes up a smaller percentage of muscle protein, the main bound form). Glutamine has been called a "conditionally essential" nutrient (1-6), because it is non-essential in normal situations (manufactured by the body in adequate quantities; not required in the diet), but in severe illness or injury becomes insufficient (there is then a need for supplementation from the diet or other sources).
Dietary glutamine is especially prevalent in wheat and beans and in protein isolates, such as those used for making nutrition bars and beverages: glutamine makes up 6-9% (by weight) of soy protein and milk protein (casein, whey) isolates. Glutamine is manufactured in the body from glutamate and ammonia by the enzyme glutamine synthetase; the process takes place mainly in the skeletal muscles.
The connection of glutamine to the musculature is of special interest. The amount of glutamine in reserve for release as needed is directly related to muscle mass: more muscle mass means more glutamine is available for metabolic processes. It is possible that one of the benefits of muscle-building exercise for good health is the increased availability of glutamine during times of stress. Under conditions of metabolic stress, including injuries, illness, and even severe emotional distress, the level of glutamine in the body declines markedly, which is thought to adversely influence resistance to infectious diseases. Persons who maintain a relatively large muscle mass may have a greater ability to withstand and recover from stressful events. Chronic illness and lack of exercise work together in a vicious cycle: poor health makes it more difficult to exercise, leading to lower muscle mass and lower glutamine stores, contributing to a higher incidence of health problems and slower recovery.
Aside from lack of exercise (which may be a lifestyle choice or the result of paralytic or debilitating diseases and injuries), there are several muscle wasting diseases, including cancer, AIDS, and pulmonary obstructive diseases. In such cases, glutamine levels can be insufficient and contribute to the overall pathology. This deficiency of glutamine, related to muscle wasting, may be partially rectified by consuming extra glutamine daily to replace the muscular manufacture of this amino acid. Additionally, glutamine administration at high doses may be associated with increased production of growth hormone, which contributes to increasing muscle mass.
The reasons that the body retains such high levels of glutamine are not fully known, though the number of biochemical reactions that take place in the body involving glutamine is quite large. Amino acids are defined, in part, by the presence of a nitrogen group in a small acidic molecule. Glutamine has two nitrogen groups, one of which, a terminal NH2, is easily separated and transferred to other molecules (leaving glutamate as the amino acid, which has an oxygen atom in place of the extra nitrogen group). Glutamine has been described as the most important circulating nitrogen shuttle, accounting for about one-third of all amino acid nitrogen transported by the blood. By contributing to the formation of many useful compounds, the circulating glutamine brings metabolic fuel to the various organs
(see Figure 1). It also transports ammonia in a non-toxic form for excretion (the ammonia is linked to glutamate to form the glutamine). In the kidneys, glutamate is the end product when the ammonia is released (to yield urea) under the control of the enzyme glutaminase.
One of the well-established roles of glutamine in human health is its contribution to the integrity of the intestinal mucosa. This role is partly related to the fact that glutamine is a critical nitrogen source for rapidly dividing cells, such as those that line the gastro-intestinal tract. The principal location of glutamine consumption in the body (i.e., where it is broken down to glutamate at the highest rate) is in the small intestine. During times of stress, the small intestine responds by utilizing more glutamine and by more efficiently transporting glutamine that has been ingested.
One of the damaging effects of cancer chemotherapy is the inhibition of these cells that line the gastro-intestinal tract, leading to a variety of adverse symptoms, such as nausea, loss of appetite, and reduced absorption of nutrients. Glutamine has been used therapeutically to protect against the toxic effects of methotrexate and other chemotherapy drugs. Glutamine is a useful adjunct to patients undergoing bone-marrow transplant procedures (e.g., intensive chemotherapy to prevent rejection), for which it is reported to improve recovery, reduce infections, and minimize complications.
Intestinal surgery, such as that done to remove tumors or to remove ulcerated portions of the intestines, greatly damages the normal mucosal production, leading to slow healing. Glutamine has been used as a means of aiding recovery from intestinal surgery. Small intestine disorders, such as ulcers and bleeding (as occurs with Crohn's disease), may also benefit from extra glutamine administration. Glutamine should not be considered a cure-all for gastro-intestinal disorders, or any of the other conditions for which it has been indicated. Rather, if there are indications of glutamine deficiency (e.g., low muscle mass, high levels of stress, persisting and/or severe intestinal disorder), then it is a reasonable therapeutic strategy to apply.
Glutamine is also considered important for the maintenance of the renal tubules, contributing to the healthy function of the kidneys. Glutamine's metabolic activities in the kidneys helps assure elimination of acids from the blood. Although not yet subject to research, kidney-damaging drug therapies might be made more safe by providing extra glutamine, especially in patients who have low muscle mass.
As a fuel for rapidly dividing cells, glutamine makes a contribution to the immune system, especially in the rapid production of white blood cells during an infection. The immune system impairment that occurs after severe burns and surgical interventions is thought to be partly due to a rapid decline in glutamine that is part of the stress reaction, resulting in lowered immunological responsiveness. Supplementation of glutamine has been proposed as a means of preventing this consequence of injuries. Glutamine is already a therapy for patients with multiple organ failure and for multi-trauma patients.
It has been reported that patients who require IV-feedings due to advanced disease conditions show improvement in mood when glutamine is included in the solution. This change may be due to the improvements in overall physiologic conditions brought about by the higher glutamine levels.
The powerful antioxidant glutathione is comprised of three amino acids: glutamate, cysteine, and glycine. Glutamine is described a "glutathione-sparing" agent, helping to maintain adequate levels of glutathione by providing adequate glutamate for its production. Glutathione deficiency tends to arise with glutamine decline (e.g., with muscle wasting) and is compensated for by administering glutamine. Glutathione is thought to contribute numerous protective effects from the adverse effects of oxidative stress and has been proposed, when administered as a supplement, to help inhibit the development of cancer, gastric ulcers, and other diseases. While glutathione taken as a supplement is very expensive and poorly absorbed, glutamine is far less expensive and easily absorbed.