Glutamine is virtually non-toxic even in very large quantities. It is rapidly metabolized and does not increase blood glutamine or ammonia above their normal levels. Studies done on normal volunteers demonstrated that ammonia, glutamate and hormonal concentrations, and nitrogen balance were not changed during glutamine-enriched parenteral nutrition1. The only known contraindication to supplementation is end stage liver or renal disease requiring a restriction of protein intake.
Short Bowel Syndrome, Inflammatory Bowel Disease, Anastamosis Support, Infectious Enteritis, Parenteral Nutrition
The intestinal mucosa provides an important barrier against toxins and bacteria. When infective organisms pass through the GI tract, such as in leaky gut syndrome, then mesenteric lymph nodes, which are rich in immune cells, destroy these organisms. In severe intestinal infections, when infective organisms pass through this barrier, immune cells in the liver act as a final barrier. Septicemia occurs, when pathogens overcome this final barrier and pass into the circulatory system, causing fever and many other serious complications.
When cells of the GI tract suffer from malnutrition and start degenerating, they can no longer function as an adequate immune system and bacteria can pass into the blood stream. Roth and colleagues observed that survival of patients with abdominal sepsis was related to free intracellular glutamine concentration, which drops precipitously during periods of increased metabolic stress.2
Dietary glutamine is essential in maintaining normal function of the entire GI tract. Glutamine helps maintain normal intestinal permeability and mucosal cell regeneration and structure. During infections of intestinal origin, immune cells need more glutamine, and hepatic glutamine consumption can rise about ten-fold. Intestinal infections can result in muscle wasting, as muscle tissue is broken down to supply glutamine.
Glutamine supplementation is used to protect and heal the GI tract, prevent GI atrophy and reduce incidence of bacterial infection and sepsis.
Current research supports the role of glutamine in healing GI cells, decreasing oxidant damage in susceptible tissues by increasing and maintaining plasma glutathione levels and as an anti-inflammatory agent.
Glutamine supplementation is particularly important after bowel surgery to help the surgical site heal, and is frequently recommended prior to the actual surgery to help strengthen the cells of the intestinal tract. Glutamine helps maintain the integrity of the bowel wall thereby preventing the transfer of bacteria into the blood stream.
There is much clinical evidence (parenteral and enteral administration) showing the importance of glutamine in GI disorders (IBD etc). It is a critical nutrient for catabolic patients3
Parenteral Nutrition and Glutamine
Total parenteral nutrition (TPN) can quickly lead to glutamine deficiency and complications, such as increased bowel permeability (allowing bacterial infections), malabsorption and diarrhea. Research indicates that providing glutamine to TPN patients can maintain GI cell morphology and function, significantly reducing these complications. Patients with short bowel syndrome, previously dependent on TPN, have had their TPN discontinued or significantly reduced using enteral glutamine supplementation. At the Nutrition Restart Center in Hopkinton, Massachusetts, patients are treated with glutamine supplementation, achieving positive results4,5.
In one publication, rat jejunal permeability was studied after total parenteral nutrition (TPN) with or without glutamine supplementation. Glutamine was found to prevent jejunal permeability and TPN-associated atrophy6.
TPN is often required in short bowel syndrome to prevent dehydration, electrolyte disturbances, and malnutrition on a chronic basis. Long – term TPN may result in the following complications: sepsis, thrombosis, nutrient deficiency and small bowel bacterial infections. Glutamine and other substances – GH and fiber have been shown to either directly or indirectly influence nutrient absorption. Growth of villi in the intestine is promoted thus promoting absorption of nutrients across the remaining bowel.
Studies have shown that this type of intestinal rehabilitation of TPN – dependent patients with intestinal failure results in an 80% reduction in TPN use with discontinuation of TPN and resumption of eating through normal means in approximately 50% of patients at long – term follow – up. Several specialized centers have emerged to serve these patients.
In chronic GI tract disease, glutamine supplementation can relieve symptoms such as diarrhea, bloating, and intestinal discomfort. Glutamine can also help with elimination problems associated with irritable bowel syndrome. Therapeutically, glutamine is used widely in the recovery and treatment of GI disorders including Crohn’s disease, irritable bowel syndrome, enteritis, short bowel syndrome, and mucosal ulceration. If glutamine intake is inadequate with such conditions, skeletal muscle tissue is used as a source of glutamine7.
A normal diet will provide 3.5 to 7 grams of glutamine per day, which is sufficient for a healthy GI tract. More glutamine is often needed to maintain normal glutamine levels and GI tract health when the intestine is under stress, due to infections, trauma, inflammation or food allergy. An extra 10 to 40 grams of glutamine per day, under these conditions, may be needed just to maintain normal intestinal structure and function.
Seriously ill patients requiring intravenous feeding were more likely to get off IV feeding when given high oral doses of glutamine (50 grams per day).
Maintenance for chronic GI Disorders is generally 5-10 grams glutamine daily.
Severe malabsorption with high levels of diarrhea, 30 grams glutamine daily (10 grams t.i.d.)
Glutamine decreases endotoxin levels in experimental animals and the authors suggest that a glutamine-rich diet may be beneficial to patients with IFB8.
Glutamine is a precursor to glutathione and was found to maintain glutathione levels and to protect the liver in experimental animals, who were subjected to liver toxins (acetaminophen)9.
In experimental animals, glutamine prevents or delays endotoxin-induced permeability changes10.
As an adjuvant to chemotherapy and GI radiotherapy side-effects such as diarrhea and in the treatment of breast cancer
Glutamine has been demonstrated to maintain the structure and integrity of the GI tract during cancer therapy and reduce the debilitating effects of such therapy. Glutamine supplementation has been shown to decrease radiation enteritis, chemotherapy induced nausea, vomiting and diarrhea, and the mouth sores that often accompany cytotoxic treatment. Again, maintaining the health of the mucosal lining of the gastrointestinal tract is pivotal in maintaining the health of the individual.
Glutamine can help alleviate the nausea/vomiting/diarrhea syndrome associated with chemotherapy and radiation treatment.
Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism
Glutamine has been shown to increase the therapeutic index of methotrexate in rats, by decreasing tumor glutathione and increasing or maintaining host glutathione. Low glutathione levels makes tumors more susceptible to chemotherapy. The authors conclude that oral glutamine supplementation may enhance the selectivity of antitumor drugs by protecting normal tissues from and possibly sensitizing tumor cells to chemotherapy treatment-related injury11.
Malnutrition and infection are common among patients receiving bone marrow transplant.
In a randomized, double blind study glutamine was shown to improve nitrogen retention and reduce the incidence of clinical infection in a group of 45 bone marrow transplant patients12.
In another study glutamine supplementation was found to replete glutamine stores and promote muscle glutamine metabolism without stimulating tumor growth13. In one animal study, rats with breast cancer were given glutamine at a dose of 1g/kg/ day. Tumor growth in treated animals was 40% less than controls and natural killer cells had 2.5 times the activity in untreated animals. Furthermore, there was a 25% increase in glutathione levels and a decrease in inflammatory prostaglandins (PGE2), which are known to promote tumor growth.
5-10 grams glutamine per day, prior to chemotherapy and/or radiotherapy, with an increase to 30 grams glutamine daily (10 gram t.i.d.) during actual therapy.
To relieve diarrhea, induced by protease inhibitor treatment and in the maintenance of muscle mass
30 grams glutamine (10 grams three time a day) Higher amounts may be required if intestinal repair and wasting are coincident.
As a support for patients with burns, trauma, septicemia, and chronic wounds and ulcers
Glutamine demand is particularly high in critical illness (trauma, burns, septicemia and inflammatory conditions). If glutamine is not supplemented, then glutamine reserves will be drawn from muscle and lead to muscle wasting.
During starvation, the liver and intestine cooperate in balancing glutamine needs. The gut uses the extra glutamine generated by the liver during starvation and converts it to alanine, which is then used by the liver to form glucose. This mechanism provides energy for both organs and also helps prevent the loss of muscle during starvation.
Glutamine and alpha-ketoglutarate were found to prevent the decrease in muscle free glutamine concentration and influence protein synthesis after total hip replacement (Total hip replacement can be used as a trauma model, with characteristic changes in the muscle amino acid pattern and protein synthesis 24 hours postoperatively)14.
Glutamine is the most abundant amino-acid of muscle tissue, constituting 50% of the amino-acid pool of the tissue. Glutamine depletion can occur in strenuous exercise, bodybuilding. Glutamine also protects muscle tissue from cortisol-induced muscle catabolism. High levels of cortisol are found under conditions of stress – either physical or emotional. In these cases, supplemental glutamine can help repair muscle injury by providing nitrogen for amino-acid and protein synthesis, and generally can serve as an anabolic agent for the whole body. In addition, glutamine provides energy for immune cells, which may be impaired, after strenuous exercise and thus render the athlete more prone to infections. Glutamine is an important source of fuel for the heart, where it is converted into glutamate, which provides a source of ATP. Glutamine also is a source of the dipeptide glycyl-l-glutamine – a type of beta-endorphin. Glycyl-l-glutamine is important for regulating blood pressure, prevention of cardiorespiratory depression and activation of natural killer cells. Glutamine supplementation before sleep, stimulates release of growth hormone, which promotes skeletal muscle repair.
Glutamine serves as a non-carbohydrate source of energy. Glutamine is also a gluconeogenic amino-acid – i.e. it can break down to provide glucose to the body, a process which takes place mostly in the liver.