For Patients & Caregivers
How It Works
Glutamine may be helpful for preventing some symptoms related to cancer treatments, such as oral inflammation. Combined with other nutrients, it may help prevent muscle wasting and weight loss in patients with advanced cancer and AIDS, but more research is needed.
Glutamine is the most abundant amino acid in the human body. It is made by most body tissues and is also found in foods such as wheat, corn, barley, peanuts, soybeans, and milk. Glutamine is important for several bodily functions, like acting as building blocks for protein. When the body is malnourished or breaks down its own muscle protein, known as cachexia, taking extra glutamine can help restore body levels and prevent adverse health effects. For example, glutamine is the major fuel source of cells that line the intestinal tract, and is therefore important in maintaining GI function. It is also the major fuel source for certain cells used in the body’s immune defense. It removes excess toxic ammonia from the body and synthesizes glutathione to help detoxify foreign substances in the liver.
Glutamine may help treat muscle wasting in patients with advanced cancer and AIDS and prevent oral inflammation related to certain cancer treatments. Initial studies also suggest it may help chemotherapy-related nerve pain. Larger well-designed trials are needed to confirm these effects.
To prevent cachexia (muscle wasting) in advanced cancer and AIDS
Small studies show that a combination of glutamine, arginine, and beta-hydroxy-beta-methylbutyrate (Juven®) can promote weight gain in these patients, but the long-term effectiveness is not known.
To prevent mucositis caused by cancer-related treatments
Several studies suggest that oral glutamine supplementation may be helpful as supportive care for inflammation of oral mucous membranes caused by cancer treatments. Larger confirmatory trials are needed.
To reduce chemotherapy-induced gastrointestinal toxicity
One study showed that glutamine given intravenously to patients receiving chemotherapy for gastric or colorectal cancer significantly reduced nausea, vomiting, and diarrhea.
To treat chemotherapy-related neuropathy
Preliminary studies suggest that glutamine may help treat neuropathy caused by chemotherapy. But larger trials are needed.
To improve tissue integrity
Clinical research supports the use of intravenous glutamine to enhance the integrity of intestines in critically ill patients.
To stimulate the immune system
Although glutamine is a necessary fuel source for lymphocytes, a type of immune cell, there is no solid evidence that glutamine supplements can stimulate the immune system in healthy people. In some studies, intravenous glutamine helped improve immune status, prevent infection, and prevent depletion of intestinal immune cells in critically ill patients and those recovering from surgery.
Intravenously, to improve recovery from surgery
Several clinical trials support this use.
- Some studies in cancer patients suggest that oral glutamine is well tolerated. However, others that used specific oral preparations reported adverse events including swelling, gastrointestinal symptoms, headache, fever, and infections.
- Severe abdominal pain and scleral icterus: In a 35-year-old female athlete following consumption of glutamine powder for three weeks. Testing suggested liver toxicity, but the patient recovered successfully after discontinuing glutamine.
For Healthcare Professionals
Glutamine is an amino acid that can be absorbed from food sources and synthesized and stored, mainly in the muscle and in the lungs. It is the building block of protein and a major cellular fuel source. Although abundant in the body, patients with cancer and AIDS-related cachexia or those recovering from catabolic states such as surgery, sepsis, and intense exercise may need to increase intake. Parenteral supplementation is used in hospitals, but oral formulations are available as medical food products. Glutamine is also marketed as a dietary supplement to enhance muscle building, wound healing, and for intestinal and immune system health.
Glutamine improved nitrogen balance, preserved intestinal integrity (1) (2), maintained intracellular glutamine levels, and reduced hospital stay in post-surgical or critically ill patients (3) (4) (12) (13) (40), but did not prevent new infections (5). In patients with postinfectious irritable bowel syndrome (IBS), glutamine supplements reduced all major IBS-related symptoms (36); and perioperative intravenous glutamine restored renal arginine synthesis resulting from abdominal aortic surgery (6). When used in total parenteral nutrition, glutamine improved nutritional status and reduced mortality and complications (7) (8), but effects in infants with gastrointestinal disease were minimal (9) (10). Preliminary studies of supplementation for brain development in preterm infants yielded promising results, but more research is needed to determine long-term effects (41). Among patients with sickle cell anemia, treatment with glutamine resulted in significantly fewer pain crises (35).
Despite its popularity, evidence is lacking to support benefits of glutamine for increasing muscle mass and strength (42).
In oncology settings, glutamine has been shown useful against cachexia (11), peripheral neuropathy (14) (15), mucositis (16) (17) (18) (19), and gastrointestinal toxicity (20). Intravenous glutamine also significantly reduced chemotherapy-induced nausea, vomiting, and diarrhea in patients with gastric or colorectal cancer (21) ; and enteral nutrition that includes arginine , glutamine, and omega-3 fatty acids may improve short-term survival in stage IV gastric cancer patients (22). It was reported effective against morbidity due to radiation in breast cancer patients (23), and conclusions from a meta-analysis indicate that glutamine reduces duration but not severity of diarrhea (24). Additional studies showed its effectiveness in reducing the incidence and severity of chemo-radiotherapy-induced oral mucositis and dysphagia in patients with oropharynx and larynx carcinoma (37); for delaying onset of esophagitis in non-small cell lung cancer patients (38); and a supplement containing HMB, L-arginine and glutamine was found to be effective in preventing sorafenib-associated hand-foot skin reaction in patients with advanced hepatocellular carcinoma (39). However, a meta-analysis reported lack of strong evidence of effectiveness for prevention and/or treatment of oral mucositis in cancer patients (43); a systematic review cited the need for well-designed trials to determine utility against gastrointestinal mucositis (44); and conflicting data indicate no impact of perioperative glutamine use on post-surgical complications or infections in gastrointestinal cancer patients (25). Furthermore, findings suggest a role for glutamine in tumor cell growth and maintenance (26) (27). More research is needed to resolve the ambiguity.
Mechanism of Action
Glutamine is essential for the maintenance of intestinal mucosal integrity and function (1). It maintains immune function by serving as the principle metabolic fuel for cells, acts as a precursor for protein synthesis, and along with cysteine and glycine, is involved in glutathione (GSH) synthesis. Intravenous glutamine preserves liver and intestinal glutathione stores in animal models of oxidant damage. Glutamine is also involved in nitrogen exchange, as it neutralizes and eliminates excess ammonia formed during protein catabolism. As a nitrogen donor, it contributes to the synthesis of other non-essential amino acids, including the purines and pyrimidines, and is therefore essential for the proliferation of most cells (29). It also plays a supportive role during biochemical stress and sepsis. Reduced oxidative stress and sickle cell-related pain with l-glutamine is attributed to increased proportions of the reduced form of nicotinamide adenine dinucleotides in sickle cell erythrocytes (35).
Although the mechanism underlying benefits against cachexia is unclear, it is thought that glutamine, a modulator of protein turnover, enhances net protein synthesis (11). Clinical evidence suggests that total parenteral nutrition supplemented with glutamine improves nitrogen balance, maintains the intracellular glutamine pool, enhances protein synthesis, and prevents deterioration of gut permeability in post-surgery patients (12).
Glutamine prevented genotoxic and clastogenic damages caused by cisplatin in mice (30). It may also potentiate the tumoricidal effect of methotrexate (MTX) since polyglutamation of MTX impairs its efflux from tumor cells and reduce its accumulation in the gut (31). The supplemental intravenous form lead to increases of GSH in the gut, but not in tumors, in a sarcoma-bearing rat model.
However, other findings show that glutamine transporters are upregulated in tumor cells and that glutamine acts as a mitochondrial substrate and promotes protein translation. This indicates tumor cell dependence for growth and maintenance (26). In addition, glutamine helps cancer cells survive acidic stress through enzymatic deamidation rather than provide nutrition (27).
- Some studies in cancer patients suggest that oral glutamine is well tolerated (14) (17) (18) (19). However, others that used specific oral preparations reported adverse events including peripheral edema, gastrointestinal symptoms, headache, fever, and infections (32) (33).
- Severe abdominal pain and scleral icterus: In a 35-year-old female athlete following consumption of glutamine powder for three weeks. Testing suggested hepatoxicity, but the patient recovered successfully after discontinuing glutamine (45).