What is Glutamine and what does it do in the body?

Glutamine is the most abundant amino acid in the blood and muscle tissue. It makes up about 6% of mixed whole body protein. It is unique among the other amino acids in that it is a preferred fuel of rapidly dividing cells, including intestinal and immune cells. Amino acids can be essential, non-essential, or conditionally essential. Essential means that it is not produced in the body and must be obtained in the diet. Non-essential means that it is produced in the body and does not need to come from the diet. Conditionally essential means that healthy people can produce enough in the body where they do not need to consume it in their diet, but under certain conditions, it is essential to have in the diet. Some of these conditionally essential conditions for glutamine include stressed states such as burns, septicemia, endotoxemia, intestinal failure, and critical illness. 

Glutamine is involved in the transport of circulating amino nitrogen and is an important intermediary that helps with accelerated gluconeogenesis from anion acids that are released by the skeletal muscle during stress states. Glutamine is also used as a precursor for DNA and glutathione synthesis. It is also one of the principal fuels used by the cells of the intestinal lining, and accounts for 35% of enterocyte energy production.  

 

 

Glutamine helps with intestinal repair and protection in the body. Both animal and human studies have shown that glutamine stimulates intestinal mucosal growth and protects from atrophy of the mucosa. Glutamine also prevents intestinal mucosal damage and was shown to decrease bacterial leakage across the intestine after they are damaged, most likely by stimulating repair of the intestinal lining. Glutamine is able to do these functions presumably by strengthening the epithelial tight junctions and by preventing paracellular permeabilities through an epidermal growth factor receptor-dependent mechanism.

 

 

 

 In one study with intestinal epithelium cells treated with acetaldehyde to compromise barrier function, the cells were treated with L-glutamine, D-gluamine, L-asparagine, L-arginine, L-Lysine, or L-alanine, and only the L-glutamine group demonstrated a benefit by decreasing aldehyde effects on transepithelial resistance. Glutamine decreased permeability at a dose-dependant rate, reduced acetaldehyde-induced disturbance of transmembrane structures, such as occludin, zonula occludens-1, E-cadherin, and B-catenin from the intercellular junctions, and induced a rapid increase in the tyrosine phosphorylation of the edipermal growth factor receptor. 

Glutamine also plays a role in acid-base balance in the body. Glutamine is made from glutamate and the toxic alkaline waste product, ammonia, with the help of the enzyme glutamine synthetase, which requires ATP and magnesium. When ammonia levels are high, the body clears ammonia from the blood by synthesizing glutamine. On the other hand, if the blood is too acidic, glutamine can be broken down into glutamate and ammonia, which increases blood pH. Ammonia can bind hydrogen ions to produce ammonium cations, which can be excreted in the urine along with chloride anions. Simultaneously, bicarbonate ions are released into the blood stream. Studies have shown that relatively small doses of glutamine can elevate plasma bicarbonate concentrations in healthy adults (Remember bicarbonate is the base the body uses from the kidneys to raise the body’s pH). 

 

 

Glutamine helps replete the stores of glutathione in the body when they are depleted. Glutathione is a tripeptide made of glutamate, cysteine, and glycine. Glutamine is a reservoir source of glutamate in the body (since it is made of glutamate and ammonia) so the availability of glutamine helps with the regeneration of glutathione stores in the liver during hepatic injury, in skeletal muscle after major trauma, sepsis, or surgery, and in chemotherapy-injured heart muscle. Glutamine can enhance the intracellular depletion of glutathione. Animal and human studies have shown that glutamine can help replenish glutathione stores during hepatic injury and surgery. 

Glutamine also plays a role in protein sparing because it is a regulator of muscle proteolysis and thus can attenuate loss of protein in the muscle when supplemented. 

Glutamine also has an immune-modulating effect by enhancing interleukin-6 levels and lymphocyte function. IL-6 plays a major role in the final differentiation of B-cells into immunoglobulin secreting cells, nerve cell differentiation, and acute phase reactants in hepatocytes. Studies have shown that the ability of lymphocytes to proliferate and generate lymphokine-activated killer cell activity is dependent on glutamine. Additionally, glutamine showed enhanced lymphocyte activity in patients who received high doses of chemotherapy after stem cell transplantation for hematologous malignancy. 

What is glutamine used for?

Glutamine is used for conditions with intestinal permeability including chronic urticaria, inflammatory bowel disease, celiac disease, liver and biliary cirrhosis, cases of portal hypertension, systemic sclerosis, diabetes, rheumatologic disorders, cystic fibrosis, alcohol overuse, adult and child asthma, HIV/AIDS, no nsteroidal anti-inflammatory drug-treated arthritis, moderate to major burns, corticosteroid use, cardiopulmonary bypass patients, and acute metal toxicities. As discussed above, glutamine can help reduce intestinal permeability, so it can be useful for all the above conditions where increased intestinal permeability is present. To read more about leaky gut related to gastrointestinal pathology, check out our blog post Digestion 101-Physio and Pathophysiology-Part III.

 

 

Glutamine can be helpful for infectious diarrhea. Glutamine helps to augment sodium and water absorption and to enhance blood glucose and body weight. Studies have shown that glutamine treated individuals had shorter duration of diarrhea than placebo. Glutamine may also be helpful for enhancing repair of mucosal injury caused by infections and toxic agents. 

Glutamine may be helpful for post surgical complications of the gastrointestinal tract. Patients undergoing abdominal surgeries including gastrectomies, sigmoidectomies, cholecystectomies, and rectal resections are at risk for developing intestinal failure or short bowel syndrome (SBS). In SBS, a serious malabsorption of fluid, electrolytes, and other nutrients can occur. Surgery trauma can also compromise intestinal mucosa so that bacteria and endotoxins can easily transfer through the intestinal wall and invade tissue and blood. Through inflammatory mechanisms, bacteria, and endotoxin septic conditions, the intestinal barrier can be affected and cause further damage. 

In one study, patients with SBS treated with growth hormone, diet changes, and glutamine increased total caloric absorption from 60-75%, protein absorption from 49-63%, carbohydrate absorption from 60-82%, water absorption from 46-65%, and sodium absorption from 49-69%. In another study with glutamine supplementation in abdominal surgery patients, the glutamine group had decreased intestinal permeability compared to an increase in the placebo group. Also, serum markers of endotoxin, diamine oxidase, and malondialdehyde concentrations were significantly decreased in the glutamine group compared to placebo, as well as temperature, heart rates and white blood cell counts seen as lower in the glutamine group. 

Ischemia reperfusion of the gut is a common occurrence in trauma, burn, septic shock, cardiac or aortic surgery, and liver or small bowel transplants. Glutamine supplementation may protect the intestines from morphological and functional mucosal injury after intestinal ischemia reperfusion. It may also prevent intestinal permeability and the incidence of bacterial translocation. 

Glutamine can be helpful for side effects from chemotherapy and radiation. Chemotherapy and radiation can injure rapidly dividing intestinal cells. When glutamine was used during chemotherapy and radiotherapy, it reduced the degeneration of intestinal mucosa, prevented intestinal mucosal injury, protected liver function through enhanced glutathione biosynthesis, and storage and hepatic tissue, increased immune function, and reduced intestinal permeability.

In chemotherapy patients with head and neck cancer, mouth sores, and swallowing difficulty are common. Glutamine during and after chemotherapy may help to decrease the incidence of mouth sores. When given in an aqueous solution to swish in the mouth, significant improvement was observed in the glutamine group, and the duration of mouth pain was less with glutamine supplementation.

In esophageal cancer patients, glutamine supplementation enhanced lymphocyte mitogenic function, and reduced permeability of the gut during radiation and chemotherapy. In patients who underwent bone marrow transplant, and myelosuppressive chemotherapy for acute myeloid leukemia found that glutamine therapy may improve neutrophil recovery. Finally, cardiac function is commonly affected during chemotherapy and radiation treatment. Glutamine may be helpful in improving cardiac function through its ability to maintain cardiac tissue glutathione levels.

 

 

 

Another common issue related to cancer is cachexia caused by accelerated protein breakdown, and slowed protein synthesis. One of the reasons for this may be due to glutamine being taken up by the growing tumor, which leaves the host with a deficiency of glutamine that can lead to cachexia. Studies have shown that when combining glutamine with a leucine metabolite and L-arginine, patients gained back body mass. Similarly to the way glutamine may support cachexia, it may also help patients with HIV infection because glutamine may help increase body mass, reverse malabsorption, and protect the small intestine. 

Chronic metabolic acidosis is a common problem in catabolic states such as sepsis, shock, and diabetes. Since glutamine becomes an essential amino acid in catabolic states because the increased demand exceeds the body’s capacity to synthesize glutamine, glutamine supplementation may be useful for maintaining pH balance in patients with acidotic conditions. 

Glutamine is also very supportive for peptic ulcers. Cabbage juice, which is a key source of glutamine, has been shown to be very successful in the treatment of peptic ulcers. Studies with glutamine supplementation have shown that glutamine helps to bring complete healing of peptic ulcers in most patients within 4 weeks. 

Glutamine may also be helpful for severe burns. Plasma glutamine levels are decreased after severe burns in adults. Burn victims given glutamine have shown better intestinal repair, a higher quality of wound healing, and reduced hospitalization. 

Glutamine may also be helpful for weight lifting and exercise due to its anabolic effect on skeletal muscle. Glutamine supports glutathione reserves, protein catabolism, and intestinal integrity, which make it useful for exercise and strength training. Glutamine has been shown to help increase energy and decrease muscle soreness after exercise. One study showed that glutamine increases growth hormone release. However, some studies have shown that glutamine does not help to increase exercise performance, body composition, or muscle protein degradation in young healthy adults; it seems that the benefits of glutamine are mostly found in patients with chronic illness and with compromised physiology instead of healthy individuals. 

Glutamine may be supportive for sickle cell disease. Glutamine has been shown to improve NAD redox potential and NADH levels in sickle RBCs, which might decrease oxidative susceptibility of red blood cells in the disease. Research has also found that glutamine supplementation decreased the adhesion of sickle RBCs to endothelial cells. 

 

 

Glutamine can also be helpful for cravings for sugar and alcohol. L-glutamine can help with sugar cravings because it easily converts to glucose when blood sugar is low. Thus, when a craving hits for sugar or carbohydrates, L-glutamine can satiate the craving without decreasing insulin sensitivity. It can also help with sugar cravings for those with weakened immune systems and low energy because sugar consumption is most likely an attempt to boost energy. Glutamine has also been shown to reduce voluntary alcohol consumption in alcoholics. 

 

What are food sources of glutamine?

The food sources of glutamine include animal and plant proteins including beef, chicken, fish, legumes, and dairy products. Other food sources of glutamine include cabbage, miso, and bone broth. 

 

 

What are the available forms of glutamine?

The available form for glutamine is L-Glutamine. There is also a form called D-Glutamine, which is the stereoisomer of L-glutamine, but it does not have any known biological activity, so L-Glutamine is the form that is found in supplemental glutamine. 

Our available options for glutamine include L-Glutamine in capsules by Pure, Montiff, Thorne, and Biotics. In powder form, the options for L-Glutamine include Pure and Thorne. 

L-Glutamine is also found in many gut formulas, especially to support leaky gut. Some of the options for gut formulas containing glutamine include GlutAloeMine Xymogen, GlutaShield Vanilla or Chocolate Ortho Molecular, and RepairVite Apex. 

What are contraindications of glutamine?

Patients with neurodegenerative diseases such as amyotrophic lateral sclerosis and multiple sclerosis should use glutamine with caution because higher doses may contribute to glutamate levels. Glutamine may interact with antiseizure medications, including phenobarbital, phenytoin, carbamazepine, primidone, and valproic acid, because they work to block glutamate activity in the brain and glutamine can convert to glutamate.

 

What are the side effects of taking glutamine?

Side effects of glutamine may include swelling of extremities, nausea, cramping rectal pain, runny nose, dizziness, skin rash, ear or hearing symptoms, itching, vomiting, stomach or abdominal pain, gas, dry mouth, muscle or joint pain, back pain, headache, tiredness, and increased sweating. 

Minor side effects for taking glutamine for sickle cell anemia include abdominal pain, back pain, constipation, headache, and nausea. 

 

 

 

 

References

Cleveland Clinic. (2024, March 8). Glutamine, Cleveland Clinic. https://my.clevelandclinic.org/health/articles/glutamine 

Cunha, John. (2021, Sep. 10). Glutamine. Rx List. https://www.rxlist.com/glutamine/generic-drug.htm 

Haas, E.M. (2006). Staying Healthy with Nutrition: The Complete Guide to Diet and Nutritional Medicine: 21st Edition. Ten Speed Press. 

Murray, M.T. & Pizzorno, J. (2021). Textbook of Natural Medicine: Fifth Edition. Elsevier. 

Murray, M.T. & Pizzorno, J. (2012). The Encyclopedia of Natural Medicine: Third Edition. Atria.