Supplemental L-glutamine is contraindicated in those hypersensitive to any component of a glutamine-containing product.
Pregnant women and nursing mothers should avoid supplemental L-glutamine unless prescribed by a physician.
Those with renal or hepatic failure should exercise caution in the use of supplemental L-glutamine.
Doses of L-glutamine up to 21 grams daily appear to be well tolerated. Reported adverse reactions are mainly gastrointestinal and not common. They include constipation and bloating. There is one older report of two hypomanic patients whose manic symptoms were exacerbated following the use of 2 to 4 grams daily of L-glutamine. The symptoms resolved when the L-glutamine was stopped. These patients were not rechallenged, nor are there any other reports of this nature.
i Human growth hormone: Concomitant use of L-glutamine and human growth hormone may enhance nutrient absorption in those with severe short bowel syndrome. L-glutamine has orphan drug status for this indication.
Indomethacin: Concomitant use of L-glutamine and indomethacin may ameliorate increased intestinal permeability caused by indomethacin. The reported dose used for L-glutamine was 21 grams daily taken in divided doses three times a day. Further, misoprostol is reported to have a synergistic effect with this combination in ameliorating intestinal permeability.
Methotrexate: There is one report that methotrexate may decrease the possible effectiveness of supplemental L-glutamine for chemotherapy-induced mucositis. In another report, nine patients with Breast Cancer
were reported to have decreased symptoms of methotrexate-related toxicity when given supplemental L-glutamine at a dose of 0.5 gram/kilogram/day.
Paclitaxel: In one report, L-glutamine at a dose of 10 grams three times daily, given 24 hours after receiving paclitaxel, appeared to prevent the development of myalgia and arthralgia, adverse reactions of paclitaxel.
DOSAGE AND ADMINISTRATION
L-glutamine is available in capsules, tablets and powder form. It is also available in medical foods for oral and enteral nutrition use and in a dipeptide form for parenteral nutrition use. (See Glutamine Peptides.) Typical doses for those with cancer, AIDS, trauma, burns, infections and other stress-related conditions range from 4 to 21 grams daily. Those who take L-glutamine for these indications must be under medical supervision.
Those with chemotherapy- or radiation-induced stomatitis have taken doses of 2 to 4 grams twice daily or 2 grams four times daily. This was done by dissolving a given amount of L-glutamine in water or normal saline — one gram dissolves in 20.8 ml of water at 30 degrees Celsius
— and using it as a swish and swallow. Again, this must be performed under medical supervision. Since L-glutamine is unstable in water, fresh solutions should be prepared daily.
Those who use supplemental L-glutamine as a possible ergogenic aid use between 1.5 to 4.5 grams daily, taken between meals.
Capsules — 500 mg, 750 mg
Tablets — 500 mg, 750 mg, 1000 mg
MECHANISM OF ACTION
Supplemental L-glutamine's possible immunomodulatory role may be accounted for in a number of ways. L-glutamine appears to play a major role in protecting the integrity of the gastrointestinal tract and, in particular, the large intestine. During catabolic states, the integrity of the intestinal mucosa may be compromised with consequent increased intestinal permeability and translocation of Gram-negative bacteria from the large intestine into the body. The demand for L-glutamine by the intestine, as well as by cells such as lymphocytes, appears to be much greater than that supplied by skeletal muscle, the major storage tissue for L-glutamine. L-glutamine is the preferred respiratory fuel for enterocytes, colonocytes and lymphocytes. Therefore, supplying supplemental L-glutamine under these conditions may do a number of things. For one, it may reverse the catabolic state by sparing skeletal muscle L-glutamine. It also may inhibit translocation of Gram-negative bacteria from the large intestine. L-glutamine helps maintain secretory IgA, which functions primarily by preventing the attachment of bacteria to mucosal cells.
L-glutamine appears to be required to support the proliferation of mitogen-stimulated lymphocytes, as well as the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). It is also required for the maintenance of lymphokine-activated killer cells (LAK). L-glutamine can enhance phagocytosis by neutrophils and monocytes. It can lead to an increased synthesis of glutathione in the intestine, which may also play a role in maintaining the integrity of the intestinal mucosa by ameliorating oxidative stress.
The exact mechanism of the possible immunomodulatory action of supplemental L-glutamine, however, remains unclear. It is conceivable that the major effect of L-glutamine occurs at the level of the intestine. Perhaps enteral L-glutamine acts directly on intestine-associated lymphoid tissue and stimulates overall immune function by that mechanism, without passing beyond the splanchnic bed.
The anticatabolic/anabolic activity of supplemental L-glutamine can be explained by its effect in sparing skeletal muscle L-glutamine stores.
Following ingestion, L-glutamine is absorbed from the lumen of the small intestine into the enterocytes. Absorption is efficient and occurs by an active transport mechanism. Some metabolism of the amino acid takes place in the enterocytes. L-glutamine that is not metabolized in the enterocytes enters the portal circulation from whence it is transported to the liver, where again some portion of the amino acid is metabolized. L-glutamine not metabolized in the liver enters the systemic circulation, where it is distributed to the various tissues of the body. L-glutamine participates in various metabolic activities, including the formation of L-glutamate catalyzed by the enzyme glutaminase. It also participates in the synthesis of proteins, glutathione, pyrimidine and purine nucleotides and amino sugars. The transport of L-glutamine into cells is via an active process. L-glutamine is eliminated by glomerular filtration and is almost completely reabsorbed by the renal tables.
INDICATIONS AND USAGE
Glutamine has been shown to be beneficial when administered in the form of glutamine peptides via TPN in some patients with varying forms of catabolic stress, e.g., some cancer, transplantation, intensive-care, surgical and immune-suppressed patients. Benefits from enteral glutamine supplementation are generally less pronounced, but preliminary significant results have been reported with the use of oral glutamine in very-low-birth-weight infants and in some major trauma patients in whom glutamine seems to strengthen immunity, particularly in the gastrointestinal tract. Glutamine may help protect against some of the side effects of cancer chemotherapy and radiotherapy.
There is little concurring evidence that glutamine is an effective ergogenic aid, but there is some suggestion that it might help protect against exercise-induced immune impairment. Some dated research suggesting that glutamine might help curb alcohol craving has not been followed up. Claims that it helps prevent neurodegenerative disorders or that it modulates mood have not been substantiated.
Several well-designed studies have demonstrated that the addition of glutamine to TPN helps decrease intestinal permeability and mucosal and villous atrophy in the small intestine. Inhibition of intestinal permeability is believed to decrease microbial translocation and thus reduce infective opportunities in the gut. Increased intestinal permeability has been associated with a number of traumas, illnesses and some surgeries.
Studies have shown worthwhile reductions in length of hospital stay attributed to glutamine-supplemented TPN in bone-marrow transplantation patients and in those who had resection for colon or rectal cancer. In another study, mortality was significantly better in intensive-care patients who received TPN supplemented with glutamine than in those whose TPN did not include glutamine.
In addition, glutamine in TPN has been credited with improving nutritional status in some critically ill patients, including cancer patients. And it appears to allow for more aggressive radiotherapy and chemotherapy by protecting against some of the side effects of those treatments.
Enteral glutamine has also demonstrated positive results. In a recent placebo-controlled study, oral glutamine significantly decreased the severity and duration of painful oral mucositis (stomatitis) in autologous bone-marrow transplantation patients. It was similarly helpful in alleviating radiation-induced oral mucositis in a recent randomized pilot trial. Very-low-birth-weight infants orally supplemented with glutamine between days 3 and 30 of life had far less hospital-acquired sepsis than controls (11% versus 30%) and had better tolerance to enteral feedings.
In a placebo-controlled study examining infectious morbidity in multiple trauma patients, oral glutamine was credited with significantly reducing the incidence of pneumonia, sepsis and bacteremia. In another recent randomized study of critically ill patients, supplementation with oral glutamine was said to have significant hospital cost benefits, reducing cost per survivor by 30%.
While claims that glutamine is an effective ergogenic aid are poorly supported, there is some evidence that the substance can help protect against some of the immune impairment that is sometimes seen in exercise "overtraining." Lower resting levels of plasma glutamine have been observed in some athletes suffering from overtraining syndrome, characterized, in part, by transient immunosuppression. In a few preliminary studies, oral glutamine supplementation appears to improve some measures of immunity and to decrease post-exercise infection. Results are not consistent, however, and more research is needed.
Some dated research suggesting that oral glutamine might help curb alcohol craving has not been followed up. One study demonstrated a significant decrease in voluntary alcohol consumption in rats supplemented with glutamine. A subsequent small, uncontrolled study focused on a group of subjects with extensive history of alcoholism. Considerable improvement was noted. More research is needed.