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Doxifluridine Chemotherapy

Doxifluridine chemotherapy

Glutamine supplementation may not prevent doxifluridine-induced diarrhea and may not affect tumor response to chemotherapy. In this study, patients with advanced breast cancer receiving doxifluridine chemotherapy took either glutamine or placebo. There was no statistical difference in the number of episodes of diarrhea in glutamine and placebo groups. Also, no significant response rate or change was observed in the severity and duration of tumor growth. Glutamine supplementation did not benefit patients on chemotherapy in this study.

Bozzetti,F; Biganzoli, L; Gavazzi, C; Cappuzzo, F; Carnaghi, C; Buzzoni, R; Dibartolomeo, M; Baietta, E: Glutamine supplementation in cancer patients receiving chemotherapy: a double-blind randomized study, Nutrition. 1997 Jul-Aug; 13(7-8): 748-51

Glutamine Deficiency

Glutamine deficiency

Glutamine may enhance the immune system as well as protect tissue integrity. Critically ill patients with low plasma and tissue levels of glutamine may need glutamine supplementation. Patients with glutamine deficiency may have prolonged recovery time and prolonged illness as well as increased risk of death. Patients who cannot tolerate enteral nutrition lack an exogenous supply of glutamine and so are at even greater risk. They have an increased risk of skeletal muscle degeneration, which compromises glutamine levels even further. In this study, 24 out of 42 patients treated with glutamine had increased survival rate compared to the 14 out of 42 survivors in the control group. Glutamine supplementation may be beneficial to critically ill patients.

Griffiths, RD: Outcome of critically ill patients after supplementation with glutamine, Nutrition. 1997 Jul-Aug; 13(7-8): 752-4



Glutamine supplementation during intravenous lipid administration may prevent impaired glucose regulation associated with hyperlipidemia. In this trial, the effect of L-glutamine supplementation, an inhibitor of fatty acid oxidation, was observed in rats given intralipid infusion. All rats were infused with 10% intralipid with one of the following: saline (control), 2% L-glutamine, or 2% L-alanine. In the control group, plasma free fatty acids (FFA) was increased from 0.74 to 1.34mmol, and plasma glucose levels increased from 125 mg/dL to 170 mg/dL. Plasma insulin levels also rose from 337 to 1278pg/mL. L-glutamine added to the high-dose lipid infusion inhibited changes in plasma glucose, insulin levels, and FFA but not triglyceride levels. L-alanine did not have the same effect. Glutamine supplementation in rats undergoing intravenous lipid administration prevents impaired glucose regulation associated with hyperlipidemia.

Ballard, TC; Farag, A; Branum, GD; Akwari, OE; Opara, EC: Effect of L-glutamine supplementation on impaired glucose regulation during intravenous lipid administration, Nutrition. 1996 May; 12(5): 349-54

Total Parenteral Nutrition

Total parenteral nutrition

Glutamine supplementation with home total parenteral nutrition (TPN) is not recommended. In a clinical trial, five patients received a glutamine-TPN stabilized solution. After the second, third and fourth week of the trial, three patients ceased treatment with glutamine due to an increase in liver enzyme concentrations. These concentrations returned to normal after discontinuing glutamine TPN therapy. Glutamine supplementation with home total parenteral nutrition did not benefit intestinal absorptive capacity in this study and was linked to potential hepatic toxicity.

Hornsby, Lewis L; Shike, M; Brown, P; Klang, M; Pearlstone, D; Brennan, MF: L-glutamine supplementation in home total parenteral nutrition patients: stability, safety, and effects on intestinal absorption, JPEN-J-Parenter-Enteral-Nutr. 1994 May-Jun; 18(3): 268-73

Very-low-birth-weight Infants

Very-low-birth-weight infants

According to this study, enteral glutamine supplementation may decrease hospital costs for parents with premature infants in neonatal intensive care. Among infants treated with glutamine supplements, a lower morbidity rate resulted when compared with those fed a standard formula during postnatal day 3 to day 30. Overall, the hospitalization cost was lowered among infants receiving glutamine.

Dallas, MJ; Bowling, D; Roig, JC; Auestad, N; Neu, J: Enteral glutamine supplementation for very-low-birth-weight infants decreases hospitalcosts, JPEN-J-Parenter-Enteral-Nutr. 1998 Nov-Dec; 22(6): 352-6



Glutamine may significantly reduce mouth inflammation (stomatitis) caused by cytotoxic cancer chemotherapy, according to this study conducted on 24 patients. Subjects were instructed to swish and swallow a glutamine or placebo suspension on days of chemotherapy administration and for at least 14 additional days. Glutamine-treated patients reported 4.5 less days of stomatitis than placebo-treated patients. From these results, it can be determined that low-dose glutamine during and after chemotherapy may decrease mouth pain associated with cytotoxic chemotherapy treatment.

Anderson PM, Schroeder G, Skubitz KM: Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy, Cancer (1998 Oct 1) 83(7):1433-9

Immune stimulation

Immune stimulation

Supplementation with oral glutamine may stimulate the immune system locally and systemically, according to this study conducted on 48 mice. Half the mice received a glutamine-rich standard diet, while the other half received the same standard diet without glutamine. The glutamine-fed mice exhibited a significant increase in interleukin-2 levels and a modest increase in intestinal T-cell counts after 10 days of glutamine supplementation. This increase was not seen in the non-glutamine mice.

Gismondo MR, Drago L, Fassina MC, Vaghi I, Abbiati R, Grossi E: Immunostimulating effect of oral glutamine, Dig Dis Sci (1998 Aug) 43(8):1752-4

Kidney Function

Kidney function

L-glutamine most likely plays an indirect role in accelerating renal acid secretion, rather than as a direct precursor of bicarbonate, according to this study conducted in vivo. The subject received a vehicle alone or with L-glutamine, after which point the gain in extracellular fluid volume bicarbonate was compared with renal acid elimination. While the vehicle alone did not increase extracellular fluid volume bicarbonate over the 90-min period, the L-glutamine increased plasma bicarbonate concentration and extracellular fluid volume bicarbonate by about 39+/-10 mmol. The L-glutamine also enhanced renal acid secretion and increased the glomerular filtration rate. This increase in glomerular filtration rate is most likely the cause for accelerated renal acid secretion, and the elevated bicarbonate concentrations.

Welbourne T, Claville W, Langford M: An oral glutamine load enhances renal acid secretion and function, Am J Clin Nutr (1998 Apr) 67(4):660-3

Glutathione Production

Glutathione production

Supplemental oral glutamine enhances increases glutathione fractional release in the gut, according to this study conducted on 344 rats. Some of the rats were fed chow with glutamine, while others were fed chow without glutamine. After 6 weeks, the glutamine-fed rats demonstrated a 50% increase in gut glutamine fractional uptake, and increased the gut glutathione release by approximately threefold. These results were not seen in the non-glutamine rats.

Cao Y, Feng Z, Hoos A, Klimberg VS: Glutamine enhances gut glutathione production, JPEN J Parenter Enteral Nutr (1998 Jul-Aug Jul-Aug) 22(4):224-7

Sickle-cell Anemia

Sickle-cell anemia

L-glutamine may significantly increase the NAD redox potential and NADH level in sickle red blood cells (RBC), according to this study conduced on 7 sickle cell anemia patients. Fasting blood samples were taken at baseline and after 4 weeks of therapy with 30 g/day glutamine. Significant increases were found in the NADH level and NAD redox potential, which may decrease oxidative susceptibility of sickle RBC, possibly leading to clinical benefit.

Niihara Y, Zerez CR, Akiyama DS, Tanaka KR: Oral L-glutamine therapy for sickle cell anemia: I. Subjective clinical improvement and favorable change in red cell NAD redox potential, Am J Hematol (1998 Jun Jun) 58(2):117-21

Methotrexate (chemotherapy)

Methotrexate (chemotherapy)

Cancer patients undergoing methotrexate therapy may be able to safely supplement with oral glutamine, possibly limiting the toxicity of chemotherapy, according to this study conducted on 344 laboratory rats and 9 breast cancer outpatients. The rats were randomized to 48 hours of prefeeding with either glutamine or a control solution. The rats were then given a dose of methotrexate and killed, allowing for analysis of the tumors. In the glutamine group, there was a threefold increase of methotrexate in the tumor, and a decrease in the total polyglutamated MTX in the gut. Breast cancer outpatients were then given increasing doses of glutamine during the methatrexate treatment. No toxicity was detected.

Rubio IT, Cao Y, Hutchins LF, Westbrook KC, Klimberg VS: Effect of glutamine on methotrexate efficacy and toxicity, Ann Surg (1998 May May) 227(5):772-8; discussion 778-80

Synthesis after Exercise

Synthesis after exercise

The consumption of glucose after prolonged exercise aids the removal of nitrogen from the muscles by contributing to the synthesis of glutamine and alanine, according to this study conducted on exercised and sedentary dogs. Glucose was give intraduodenally for 150 min, beginning 30 minutes after a prolonged exercise period or equivalent sedentary period. The dogs that had exercised experienced a twofold increase in limb glucose uptake compared to sedentary dogs. Arterial glutamine levels fell with the glucose load in both groups, while net hindlimb glutamine efflux increased in response to glucose in exercised dogs, but not the sedentary group.

Galassetti P, Gibbons FK, Hamilton KS, Lacy DB, Cherrington AD, Wasserman DH: Enhanced muscle glucose uptake facilitates nitrogen efflux from exercised muscle, J Appl Physiol (1998 Jun Jun) 84(6):1952-9

NSAID & Glutamine


Timely supplementation with glutamine may decrease the gastric damage caused by NSAID-induced increases in mucosal permeability, according to this study conducted on healthy volunteers. The patients underwent tests at baseline, following NSAID, and following NSAID/glutamine and/or misoprostol combination. Pre-treatment with glutamine did not prevent permeability changes. Multiple doses of glutamine close in time to NSAID-dosing lowered permeability. Co-administration of misoprostol with the multiple-doses of glutamine further lowered the induced permeability increase.

Hond ED, Peeters M, Hiele M, Bulteel V, Ghoos Y, Rutgeerts P: Effect of glutamine on the intestinal permeability changes induced by indomethacin in humans, Aliment Pharmacol Ther 1999 May;13(5):679-85

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