Glutamine Introduction

Glutamine is an amino acid that falls into the category of uncharged polar side chain amino acids. Glutamine is formed in the body from glutamate. This chemical reaction (glutamate to glutamine) is catalyzed by an enzyme called glutamine synthetase. [1] For the conversion to occur, it is driven by the hydrolysis of ATP (adenosine triphosphate), where ATP combines with an ammonium ion to form ADP (adenosine diphosphate); releasing one phosphate molecule and a hydrogen ion. This conversionary process is critical, as it is a major pathway for the detoxification of ammonia in the brain, muscle, and liver. The result of this coupled reaction, leaves glutamine with an amide linkage with ammonia at the end of the γ-carbon.

When dietary proteins are broken down (turned over) in the body, the amino acids release as a result of a chemical reaction called hydrolysis. They become part of a free group of amino acids referred to as the amino acid pool. This pool is relatively small, consisting of approximately 100 grams in the average adult male. However, glutamine and glutamate contribute to about 50% of this pool. [1] This is reflective of glutamate and glutamine participation in ammonia transport. Free amino acids go on to form body proteins, other non-protein derivatives, or participate in catabolism. As mentioned, glutamine provides a non-toxic storage and transport form for ammonia. Once it reaches the kidneys, it is removed and deaminated by the enzyme, glutaminase, and converted to both glutamate and ammonia.

Glutamine also participates in the synthesis of purine nucleotides in the body. These compounds are the backbone of DNA and RNA. Without these biochemicals, proteins could not be synthesized, cells could not divide, and human life would cease to exist. Glutamine plays a role in various bodily functions, including maintenance of intestinal structure and function, and immunity. Glutamine plays a supportive role during biochemical stress and sepsis as well.

In the past, drugs were developed to target glutamine destruction, due to the fact that some cancer cells use this amino acid as a fuel source. [2] However, because glutamine is necessary for vital bodily functions, many adverse effects resulted.

Glutamine Food Sources

Glutamine is found in an array of plants and animal tissue. However, it is susceptible to degradation when cooked. Good sources of glutamine include raw spinach and parsley. [3] Glutamine in supplemental form as a powder must remain dry or it will degrade.

Glutamine Uses

The efficacy of Glutamine as a therapeutic agent has been demonstrated in numerous health conditions. One of the more interesting applications for glutamine is in the care of critically ill and post-operative patients who have been hospitalized as a result. A study of 84 patients in an intensive care unit who could not receive enteral nutrition, were randomly divided into a glutamine parenteral formula or control group. [4] After six months, the patients receiving the glutamine formula demonstrated significantly improved survival rates. Furthermore, total ICU and hospital costs were reduced when compared to the control group.

Another study showed a significant reduction in the median post-intervention ICU and hospital patient costs, in those being administered glutamine formula. [5] A similiar randomized double-blind, placebo-controlled study in patients following major abdominal surgery demonstrated comparable findings. [6] In this study, patients were given either a total parenteral nutrition (TPN) solution containing 0.3 g/kg/day L-alanyl-L-glutamine, or a control solution. Subjects taking the glutamine solution exhibited improved nitrogen balance and improved lymphocyte recovery, as well as a shorter post-operative hospital stay versus the control group. A review of glutamine therapy in hospitalized patients concluded that glutamine supplemented TPN solutions improved nitrogen balance following cholecystectomy (gallbladder removal), and improved recovery following bone marrow transplantation. [7]

Chemotherapy can cause many adverse effects. There are many substances which continue to be investigated as possible therapies to make chemotherapy tolerable. Glutamine is one such compound that has received some interest for addressing chemotherapy. As it is important for maintenance of gastrointestinal structure and function, induced stomatitis and gastrointestinal toxicity are the conditions of primary interest regarding glutamine’s administration in persons receiving chemotherapy treatments.

One study of 14 patients with stomatitis following a course of chemotherapy was conducted to examine the effect of glutamine supplementation. [8] Subjects were given 4 grams of L-glutamine as an oral suspension, twice daily, starting the first day of chemotherapy, for a duration of 28 days; or until 4 days after symptoms from chemotherapy had resolved. The results showed that the severity of stomatitis was decreased in 12 out of 14 patients, and the mean number of days was also reduced. Another study demonstrated decreased duration and severity of chemotherapy induced diarrhea, and reduced need for parenteral nutrition when administered 6 grams of L-glutamine, orally, three times daily. [9]

Other conditions for which glutamine has been found useful include; alcohol withdrawal, peptic ulcers, neuropathies from chemotherapy, especially Taxol, recovery following intense physical exercise, depression, coronary heart disease, autoimmune diseases, malnourishment in children, colitis, and sickle cell anemia. [10-20]

Glutamine Dosages

There is no established Recommended Dietary Allowance (RDA) for glutamine. It is not an essential nutrient, meaning it can be made in the body. Normal doses of glutamine, that have been reported in study, range from 1 - 20 grams per day.

Glutamine Deficiencies and Toxicities

Glutamine Deficiency

Glutamine is biosynthesized in the body from glutamate, therefore it is not considered an essential amino acid. However, when bodily functions that require glutamine increase, the supply of glutamine may be low which would require an elevated external supply. Manganese is a cofactor in the formation of glutamine. If dietary consumption of this mineral is low, glutamine levels may not be optimal.

Glutamine deficiency induced by experimental cancer pharmaceutical agents causes weight loss, headaches, depression, loss of appetite, and cramps.

Glutamine Toxicities

Glutamine is generally considered safe, but long term studies of high doses of glutamine have yet to be conducted. Persons with liver disorders, kidney problems, Reye’s syndrome, or conditions resulting in ammonia accumulation, must avoid glutamine supplementation. [3]


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