United Press International, Asia, China
10-16-07
Health Watch: Glutamine is more than just an amino acid
DR. PRADNYA KULKARNI
Recent studies have shown a strong correlation between levels of a "nonessential" amino acid called "glutamine" in the human body and the survival of patients in intensive care units. Glutamine is one of the 20 amino acids present in the human body and is labeled as non-essential because it can be easily synthesized in our body.
Dr. Richard Griffiths of the University of Liverpool in Britain was the first to publish trials on the intravenous use of glutamine in ICU patients. He studied a group of critically ill patients fed by parentral nutrition -- a process where nutritional formulas containing salts, glucose, amino acids, lipids, and vitamins are directly injected into the patient's blood through tubes, bypassing the usual process of eating. Patients were divided into two groups -- one received glutamine in their nutrition while the other did not.
Patients were monitored for a period of 6 months even after discharge.
Griffiths noted fewer deaths in the group that had received glutamine versus those who had not. None of the glutamine recipients died from multiple organ failure and few suffered fungal infections. The findings surprised ICU specialists and intensivists.
According to Griffiths, an ICU admission is a state of great stress, which has serious consequences on the patient's health. His study proved that including parenteral glutamine in the nutritional management had positive outcomes on the recovery of such patients.
Dr. Christiane Goeters from the department of Anaesthiology and Intensive
Care at the University of Munster in Germany conducted a similar study on a larger group of ICU patients and re-asserted the importance of glutamine and its role in the reduction of deaths in critically ill patients.
Glutamine is manufactured abundantly in the human body where muscles tend to be its most important source. However, glutamine levels diminish following major surgeries, trauma, or sepsis. Studies have shown that there is a high turnover of blood glutamine in ICU patients and the demand for this amino acid increases during stress.
Historically, glutamine was not considered important in parenteral nutrition, as its behavior was not extensively studied. In addition, pharmaceutical problems in

making a glutamine solution, as it neither soluble in water nor stable in a solution, made manufacturing it for intravenous use difficult.
In order to fight infections that ICU patients generally develop, like pneumonias and organ failures or those caused by severe burns and accident injuries, the body needs a healthy army of fighter immune cells, comprising white blood cells called lymphocytes, monocytes, and neutrophils. Researchers believe that glutamine is a major fuel for these cells. Studies by Dr. Rudolf Oehler from
Surgical Research Laboratories in Vienna and Griffiths have proved that during stress, like an infection, glutamine is necessary for the optimal response of the immune cells.
Dr. Paul Wischmeyer from the University of Colorado Health Sciences Center in Denver has suggested that glutamine helps immune cells manufacture certain protective proteins, called heat shock proteins. Armed with these HSP's, lymphocytes are able to protect themselves from destructive chemicals produced during life threatening infections.
Burn patients are most susceptible to infections as they lack a very important protective barrier, the skin. Wischmeyer found that adding glutamine in their therapy reduced infections, making recovery faster. Retrospective studies have also shown that glutamine supplements reduce infections and deaths in surgical patients besides those in ICU's.
Severely ill patients also suffer from decreased responses to insulin. The resulting high blood sugar or hyperglycemia often worry physicians, as it is an additional risk for bacterial and fungal infections and an important cause of death in ICU patients. Besides, administering increased levels of insulin has its own risks. Studies by Dr. Soh Iwashita from Iowa State University and Dr. M. J.
Borel from the Department of Surgery in Nashville showed that parenteral glutamine supplements increased responsiveness to insulin and therefore reduced its need. As a result, fewer infective complications and deaths occurred.
ICU patients also suffer from multiple organ failure where several toxic chemicals called free radicals are produced. These accentuate damage by promoting the release of more toxic substances. The body usually reacts to such situations by producing anti-oxidants, which are scavengers of free radicals.
Glutathione is one such major anti-oxidant and plays a vital role in maintaining the levels of glutathione during stress. This was evident in a study on surgical patients, carried out by Dr. Jan Werneman at the Karolinska Institute in Sweden.
Glutamine thus indirectly protects our body from oxidative damage.
Research says that the effects of glutamine are best when given in large doses, evident in patients who recovered faster than those who received lesser doses. In addition, those who received it early in their treatment and for longer

periods fared better than those who did not. This proves that the body at war for longer periods needs generous doses of glutamine.
Despite understanding the role of glutamine in immune function, cell protection, DNA synthesis, and other complex metabolic processes, scientists do not yet know, how precisely glutamine works and the mechanism of its action is still a mystery.
Fortunately, this amino acid has no side effects. Dr. Ravinder Reddy, a gastrointestinal surgeon from India, noted a very amusing side effect when his ICU patients on ventilators demanded food -- a behavior not associated with ICU patients due to their drastically reduced appetite. Therefore, hunger seems to be one favorable side effect of this supplement.
However, glutamine taken through the mouth is not as effective in ICU patients as it has been when given intravenously. The reason is physiological as intestinal cells use most of it to manufacture other amino acids and for producing energy.
In addition, glutamine is flushed as a natural process by the liver. Hence, for best results, glutamine is injected parenterally. However, studies are under way to manufacture an equally effective glutamine product that can be taken orally by
ICU patients who can eat.
As muscles produce glutamine, it is easy to understand why they are such an important immune organ of our body. It also explains why elderly persons with reduced muscle mass are more prone to infections.
Glutamine supplementation is an additional expense to patients. However, benefits in terms of improved survival, fewer complications, fewer antibiotics, and reduced hospital stays are manifold compared to the price. Mauren Macburney,
Director of Nutrition Support Service at the Brigham and Women's Hospital in
Boston did a cost evaluation study on bone marrow transplant patients. Of 43 patients, 22 received glutamine supplements at an extra cost of about US$1300 per patient. However, each patient saved almost US$21,000 in hospital stays, medication, laboratory, and radiology expenses.
Though technical difficulties of producing a glutamine solution were resolved two decades ago, its usage as an indispensible amino acid supplement in critically ill patients has been accepted only recently. While its levels are high in the healthy body, they fall markedly during stress. Correcting this deficiency seems to be a powerful tool in reducing ICU related morbidities and mortalities.