Glutamine

Glutamine/Drug Interactions

  • AnestheticsAnesthetics: General anesthesia resulted in a decrease in muscle glutamine in human research (125).
  • AntibioticsAntibiotics: Glutamine in postsurgical, catabolic, or exercising individuals reduced the rate of infection (104; 97; 126; 84). In burn or critically ill patients, glutamine supplementation resulted in a reduced incidence of Gram-negative bacteremia, positive blood cultures in general, and septic complications (58; 12; 75; 8; 7). Glutamine had no effect on antibiotic use in various clinical trials (77; 9).
  • Anticachexic agentsAnticachexic agents: In patients with cancer or HIV-related cachexia, a combination of glutamine, arginine, and beta-hydroxy-beta-methylbutyrate increased weight gain and fat free mass (53; 41). This was attributed to decreased muscle protein breakdown and improved muscle protein synthesis.
  • AntidepressantsAntidepressants: In human research, antidepressant treatment was associated with increased serum glutamine (35).
  • AntidiarrhealsAntidiarrheals: In human research, glutamine induced an increase in water and electrolyte absorption or reduced secretion (127; 31). Reduced gut permeability has been shown in other glutamine-supplementation studies (128; 129; 130; 131; 132). Reduced diarrhea has been shown in clinical studies (63; 115; 80). Loperamide intake was reduced in glutamine-supplemented colorectal cancer patients treated with 5-fluorouracil and folinic acid (85).
  • Anti-inflammatory agentsAnti-inflammatory agents: In postoperative patients, parenteral glutamine decreased systemic inflammation (133; 21).
  • Antiretroviral agentsAntiretroviral agents: In human research, glutamine reduced the severity of antiretroviral agent-associated diarrhea (80; 134; 135) and increased blood levels of antiretroviral agents (135).
  • CelecoxibCelecoxib: In human research, a combination of celecoxib and glutamine had no effect on the toxicities of leucovorin (136).
  • ChemoprotectantsChemoprotectants: Glutamine 10g orally three times daily for four days starting 24 hours after completion of paclitaxel resulted in a reduction in the severity of peripheral neuropathy (137). Various human studies suggest that glutamine is associated with a reduction in side effects associated with chemotherapy (138; 14; 16; 15; 88; 90). In human research, a combination of celecoxib and glutamine had no effect on the toxicities of leucovorin (136).
  • Growth hormonesGrowth hormones: In human research, a glutamine-containing supplement increased serum growth hormone levels (32; 39). Treatment of patients with chronic illness with human growth hormone normalized plasma or muscle glutamine levels (139; 140). In recent surgical patients, combination of glutamine with growth hormone and IGF-1 resulted in a net protein gain over glutamine alone, suggesting a combination effect (2). In patients with short bowel syndrome, a combination of growth hormone and glutamine had additive effects (69; 70). Growth hormone stimulated glutamine transport across the brush border membrane in human research (141). However, infusion into the femoral artery decreased glutamine release from muscle and decreased de novo synthesis of muscle glutamine (142). The relationship of glutamine and growth hormone has been discussed by others (143).
  • ImmunosuppressantsImmunosuppressants: In human research, parenteral and enteral glutamine were associated with modifications in systemic interleukin and endotoxin production or human leukocyte antigen-DR expression on monocytes, and improvements in lymphocyte recovery (22; 144; 145; 146; 128; 147; 3; 148). Plasma glutamine was associated with the production of tumor necrosis factor (TNF) and IL-2 (48). In human and animal research, glutamine increased immunoglobulin levels in plasma and nasal fluids (17; 18; 19).
  • InsulinInsulin: Glutamine levels were increased in insulin treated patients with abnormalities of myocardial substrate metabolism during blood cardioplegic aortic cross-clamping and reperfusion (66). Fasting insulin levels increased in cystic fibrosis patients using oral glutamine (67). Glutamine increased insulin-mediated glucose disposal in trauma patients (68).
  • Interferon-alphaInterferon-alpha: In human research, the combination of interferon-alpha and a glutamine-derived agent, murabutide, appeared to have beneficial effects on anti- and proinflammatory cytokines (149). In recent surgical patients, combination of glutamine with growth hormone and IGF-1 resulted in a net protein gain over glutamine alone, suggesting a combination effect (2).
  • MethotrexateMethotrexate: Methotrexate was suggested to be the cause for a lack of effect of glutamine in allogeneic bone marrow patients (9).
  • NeurolepticsNeuroleptics: In human research, glutamine decreased the dose of neuroleptics required in hospital inpatients (47).
  • Nonsteroidal anti-inflammatory agents (NSAIDs)Nonsteroidal anti-inflammatory agents (NSAIDs): In human research, glutamine reduced intestinal permeability induced by indomethacin (150), but not aspirin (151). In animal research, glutamine ameliorated indomethacin-induced intestinal damage, including reduced oxidative stress (152).
  • OpiatesOpiates: In children undergoing stem cell transplantation, use of narcotics was decreased in those children receiving glutamine (92).
  • Protein sparing agentsProtein sparing agents: Glutamine has protein-sparing or improved-nitrogen-balance effects in infants, and nonhealthy children and adults (153; 154; 155; 156; 103; 3; 18; 105; 1; 118; 157; 8; 7).
  • SomatostatinSomatostatin: Somatostatin had no effect on plasma glutamine levels (158).
  • SulpirideSulpiride: Sulpiride had no effect on serum levels of glutamine (159).
  • Valproic acidValproic acid: In human research, there was some evidence to suggest valproate therapy is associated with increased brain levels of glutamine (160).
  • Glutamine/Herb/Supplement Interactions:

  • AntibacterialsAntibacterials: Glutamine in postsurgical, catabolic, or exercising individuals reduced the rate of infection (104; 97; 126; 84). In burn or critically ill patients, glutamine supplementation resulted in a reduced incidence of Gram-negative bacteremia, positive blood cultures in general, and septic complications (58; 12; 75; 8; 7). Glutamine had no effect on antibiotic use in various clinical trials (77; 9).
  • Anticachexic herbs and supplementsAnticachexic herbs and supplements: In patients with cancer or HIV-related cachexia, a combination of glutamine, arginine, and beta-hydroxy-beta-methylbutyrate increased weight gain and fat free mass (53; 41). This was attributed to decreased protein breakdown and improved protein synthesis.
  • AntidepressantsAntidepressants: In human research, antidepressant treatment was associated with increased serum glutamine (35).
  • AntidiarrhealsAntidiarrheals: In human research, glutamine induced an increase in water and electrolyte absorption or reduced secretion (127; 31). Reduced gut permeability has been shown in other glutamine-supplementation studies (128; 129; 130; 131; 132). Reduced diarrhea has been shown in clinical studies (63; 115).
  • Anti-inflammatory herbsAnti-inflammatory herbs: In postoperative patients, parenteral glutamine decreased systemic inflammation (133; 21).
  • AntioxidantsAntioxidants: A combination of arginine, antioxidants, omega-3 fatty acids, and glutamine had no additive effect over a high-protein enteral formula in terms of clinical outcome in an intensive care population (161).
  • Antiretroviral herbsAntiretroviral herbs: In human research, glutamine reduced the severity of antiretroviral agent-associated diarrhea (80; 134; 135) and increased blood levels of antiretroviral agents (135).
  • ArginineArginine: A combination of beta-hydroxy-beta-methylbutyrate (BHMB), glutamine, and arginine was studied for rheumatoid arthritis and was well tolerated (28). A combination of arginine, antioxidants, omega-3 fatty acids, and glutamine had no additive effect over a high-protein enteral formula in terms of clinical outcome in an intensive care population (161). A combination of omega-3 fatty acids, arginine, and glutamine was well tolerated and improved levels of serum protein and immunological response (162; 163).
  • Beta-hydroxy-beta-methylbutyrate (BHMB)Beta-hydroxy-beta-methylbutyrate (BHMB): In human research, a combination of BHMB, glutamine, and arginine was studied for rheumatoid arthritis and was well tolerated (28).
  • Branched-chain amino acidsBranched-chain amino acids: In human research, a combination of carbohydrates and branched-chain amino acids increased plasma glutamine during exercise over carbohydrate alone (164). Branched-chain amino acids resulted in an increase in muscle and plasma glutamine production during exercise (165; 166; 167; 168; 169).
  • Chemotherapeutic herbs and supplementsChemotherapeutic herbs and supplements: Glutamine 10g orally three times daily for four days starting 24 hours after completion of paclitaxel resulted in a reduction in the severity of peripheral neuropathy (137). Various human studies suggest that glutamine is associated with reduction in side effects associated with chemotherapy (138; 14; 16; 15; 88; 90).
  • Exercise performance herbs and supplementsExercise performance herbs and supplements: In human research, strenuous exercise decreased plasma levels of glutamine (170). Glutamine supplementation promoted storage of muscle glycogen following exercise, to a similar extent as oral glucose polymer (36), and enhanced exercise-induced IL-6 production (20). Glutamine increased body mass, lean body mass, and initial rate of power production in exercising adults (171). In a review, Ohtani discussed the beneficial effects of dietary amino acid supplementation, including glutamine, on muscle function, fatigue, and recovery in exercising athletes (45).
  • FiberFiber: A combination of probiotics, fiber, and glutamine reduced diarrhea associated with antiretrovirals (134).
  • Growth hormonesGrowth hormones: In human research, a glutamine-containing supplement increased serum growth hormone levels (32; 39). Treatment of patients with chronic illness with human growth hormone normalized plasma or muscle glutamine levels (139; 140). In recent surgical patients, combination of glutamine with growth hormone and IGF-1 resulted in a net protein gain over glutamine alone, suggesting a combination effect (2). In patients with short bowel syndrome, a combination of growth hormone and glutamine had additive effects (69; 70). Growth hormone stimulated glutamine transport across the brush border membrane in human research (141). However, infusion into the femoral artery decreased glutamine release from muscle and decreased de novo synthesis of muscle glutamine (142). The relationship of glutamine and growth hormone has been discussed by others (143).
  • ImmunostimulantsImmunostimulants: In human research, parenteral and enteral glutamine were associated with modifications in systemic interleukin and endotoxin production or human leukocyte antigen-DR expression on monocytes, and improvements in lymphocyte recovery (22; 144; 145; 146; 128; 147; 3; 148). Plasma glutamine was associated with the production of tumor necrosis factor (TNF) and IL-2 (48). In human and animal research, glutamine increased immunoglobulin levels in plasma and nasal fluids (17; 18; 19).
  • ImmunosuppressantsImmunosuppressants: In human research, parenteral and enteral glutamine were associated with modifications in systemic interleukin and endotoxin production or human leukocyte antigen-DR expression on monocytes, and improvements in lymphocyte recovery (22; 144; 145; 146; 128; 147; 3; 148). Plasma glutamine was associated with the production of tumor necrosis factor (TNF) and IL-2 (48). In human and animal research, glutamine increased immunoglobulin levels in plasma and nasal fluids (17; 18; 19).
  • Insulin-modifying herbs and supplementsInsulin-modifying herbs and supplements: Glutamine levels were increased in insulin-treated patients with abnormalities of myocardial substrate metabolism during blood cardioplegic aortic cross-clamping and reperfusion (66). Fasting insulin levels increased in cystic fibrosis patients using oral glutamine (67). Glutamine increased insulin-mediated glucose disposal in trauma patients (68).
  • NarcoticsNarcotics: In children undergoing stem cell transplantation, use of narcotics was decreased in those children receiving glutamine (92).
  • NeurolepticsNeuroleptics: In human research, glutamine decreased the dose of neuroleptics required in hospital inpatients (47).
  • Omega-3 fatty acidsOmega-3 fatty acids: A combination of arginine, antioxidants, omega-3 fatty acids, and glutamine had no additive effect over a high-protein enteral formula in terms of clinical outcome in an intensive care population (161). A combination of omega-3 fatty acids, arginine, and glutamine was well tolerated and improved levels of serum protein and immunological response (162; 163).
  • Ornithine alpha-ketoglutarate (OKG)Ornithine alpha-ketoglutarate (OKG): In burn and trauma patients, OKG induced an increase in plasma glutamine (172; 173).
  • ProbioticsProbiotics: A combination of probiotics, fiber, and glutamine reduced diarrhea associated with antiretrovirals (134). A combination of probiotics and glutamine in enteral feeding reduced the infection rate and length of stay in critical care (27).
  • Protein-sparing herbs and supplementsProtein-sparing herbs and supplements: Glutamine has protein-sparing or improved-nitrogen-balance effects in infants, and nonhealthy children and adults (153; 154; 155; 156; 103; 3; 18; 105; 1; 118; 157; 8; 7).
  • Weight-promoting herbs and supplementsWeight-promoting herbs and supplements: In patients with cancer-related cachexia, a combination of glutamine, arginine, and beta-hydroxy-beta-methylbutyrate increased weight gain and fat free mass, which was maintained for approximately six months (53). This was attributed to decreased protein breakdown and improved protein synthesis. Weight gain was also increased in chemotherapy-treated cancer patients given glutamine (101).
  • Wound-healing herbs and supplementsWound-healing herbs and supplements: In burn patients, glutamine improved wound healing (10). In human research, a combination of glutamine, arginine, and beta-hydroxy-beta-methylbutyrate increased collagen deposition, as reflected by hydroxyproline content, but had no effect on total protein accumulation (54).
  • Glutamine/Food Interactions:

  • Antioxidant-containing foodsAntioxidant-containing foods: A combination of arginine, antioxidants, omega-3 fatty acids, and glutamine had no additive effect over a high-protein enteral formula in terms of clinical outcome in an intensive care population (161).
  • CarbohydrateCarbohydrate: During exercise, carbohydrate maintained plasma glutamine (174; 175). During exercise, a low-carbohydrate diet resulted in decreased plasma glutamine in untrained men (176).
  • FiberFiber: Reduced diarrhea has been shown in clinical studies (63; 115). A combination of probiotics, fiber, and glutamine reduced diarrhea associated with antiretrovirals (134).
  • FishFish: A combination of arginine, antioxidants, omega-3 fatty acids, and glutamine had no additive effect over a high-protein enteral formula in terms of clinical outcome in an intensive care population (161). A combination of omega-3 fatty acids, arginine, and glutamine was well tolerated and improved levels of serum protein and immunological response (162; 163).
  • FructoseFructose: In healthy children, fructose absorption was enhanced by dietary glutamine (177).
  • Monosodium glutamateMonosodium glutamate: Monosodium glutamate consumption by adults increased plasma glutamine (178).
  • Probiotic-containing foodsProbiotic-containing foods: A combination of probiotics, fiber, and glutamine reduced diarrhea associated with antiretrovirals (134). A combination of probiotics and glutamine in enteral feeding reduced the infection rate and length of stay in critical care (27).
  • ProteinProtein: A combination of arginine, antioxidants, omega-3 fatty acids, and glutamine had no additive effect over a high-protein enteral formula in terms of clinical outcome in an intensive care population (161). A combination of omega-3 fatty acids, arginine, and glutamine was well tolerated and improved levels of serum protein and immunological response (162; 163). Branched-chain amino acids resulted in an increase in muscle and plasma glutamine production during exercise (165; 166; 167; 168; 169). Glutamine has protein sparing or improved nitrogen balance effects in infants, and nonhealthy children and adults (153; 154; 155; 156; 103; 3; 18; 105; 1; 118; 157; 8; 7).
  • Weight promoting dietsWeight promoting diets: In patients with cancer-related cachexia, a combination of glutamine, arginine, and beta-hydroxy-beta-methylbutyrate increased weight gain and fat free mass, which was maintained for approximately six months (53). This was attributed to decreased protein breakdown and improved protein synthesis. Weight gain was also increased in chemotherapy-treated cancer patients given glutamine (101).
  • Glutamine/Lab Interactions:

  • Amino acidsAmino acids: In human study, glutamine supplementation alters levels of other amino acids, including a decrease in glycine, proline, and arginine (179), or an increase in glycine, arginine, alanine, or ornithine (180; 51; 181). In human and animal study, glutamine supplementation increased plasma taurine (182). In human study, nonessential amino acids do not appear to increase following glutamine supplementation (183). Other studies show no effect on amino acids in general (184). Fish determined that glutamine-enriched tube feeding and TPN can result in similar profiles for most plasma amino acids at carefully matched doses (185).
  • AmmoniaAmmonia: In cirrhotic patients without transjugular intrahepatic portosystemic shunts, an oral glutamine load caused an increase in ammonia (64).
  • Antiretroviral agentsAntiretroviral agents: In human study, glutamine increases blood levels of antiretroviral agents (135).
  • AspartateAspartate: In human study, glutamine supplementation increased plasma aspartate (181).
  • BicarbonateBicarbonate: In human study, glutamine supplementation increased levels of plasma bicarbonate (39)
  • Blood culturesBlood cultures: In burn or critically ill patients, glutamine supplementation resulted in a reduced incidence of Gram-negative bacteremia, positive blood cultures in general, or septic complications (58; 12; 75; 8; 7).
  • Body massBody mass: In patients with cancer or HIV-related cachexia, a combination of glutamine, arginine, and beta-hydroxy-beta-methylbutyrate increased weight gain and fat free mass (53; 41). Glutamine increased body mass, lean body mass, and the initial rate of power production in exercising adults (171).
  • CholinesteraseCholinesterase: In human research, glutamine increased blood levels of cholinesterase (23).
  • CitrullineCitrulline: In human research, glutamine supplementation increased plasma citrulline (181).
  • C-reactive proteinC-reactive protein: In human research, glutamine decreased levels of C-reactive protein (23; 58).
  • D-xyloseD-xylose: In human research, glutamine supplementation increased levels of serum D-xylose as well as its excretion (186).
  • ElectrocardiogramElectrocardiogram: In human research, a single oral dose of glutamine resulted in a delayed time of onset of a more than 1.0mm of ST segment depression by 38 seconds (43).
  • EndotoxinEndotoxin: In human research, glutamine supplementation reduced blood levels of endotoxin (72; 130).
  • Free fatty acidFree fatty acid: In human research, glutamine supplementation decreased plasma free fatty acids (181).
  • GlucoseGlucose: Glutamine increased insulin-mediated glucose disposal in trauma patients (68) and altered glucose homeostasis during and after exercise (187). In animal research, glutamine induced insulin resistance in adipose tissue, improving insulin signaling in liver and muscle (188). Also, increased glutamine availability blunted the effect of insulin action on glucose production and enhanced insulin-mediated glucose utilization (189).
  • GlutamateGlutamate: In human research, glutamine supplementation increased plasma glutamate (181).
  • GlutamineGlutamine: In human research, glutamine supplementation resulted in increases in glutamine in some (2; 95; 5; 71; 179; 3; 72; 105; 36; 190; 51; 181; 107) but not all (19; 59; 39; 191) studies. In human research, gut mucosal and muscle glutamine also increased with supplementation (192; 193). In animal research, glutamine increased muscle and plasma glutamine, but not tumor levels of glutamine (129).
  • GlycerolGlycerol: In human research, glutamine supplementation decreased plasma glycerol (181).
  • Growth hormoneGrowth hormone: In human research, a glutamine-containing supplement increased serum growth hormone levels (32; 39; 39).
  • Heart rateHeart rate: In human research, glutamine reduced resting heart rate (130).
  • ImmunoglobulinsImmunoglobulins: In human and animal research, glutamine increased immunoglobulin levels in plasma and nasal fluids (17; 18; 19). One study found no effect of glutamine on levels of sIgA (115).
  • InsulinInsulin: Fasting insulin levels increased in cystic fibrosis patients using oral glutamine (67).
  • Insulin-like growth factorInsulin-like growth factor: In human research, the effect of glutamine on insulin-like growth factor was studied (33).
  • InterleukinsInterleukins: In human research, glutamine supplementation enhanced exercise-induced IL-6 production (20) and decreased IL-6 in surgical patients (21; 22). Glutamine was associated with the production of tumor necrosis factor (TNF) and IL-2 (48). Glutamine had no effect on serum levels of IL-8 (115; 22) nor reduced IL-8 (148; 144). In other research, glutamine had no effect on IL-6 or TNF (148; 144).
  • Measures of oxidative stressMeasures of oxidative stress: In human research, glutamine reduced levels of diamine oxidase and malondialdehyde (130). In human research, glutamine supplementation resulted in maintenance of presurgical levels of total and reduced muscle glutathione (26).
  • Methotrexate levelsMethotrexate levels: In animal research, glutamine was associated with increased levels of methotrexate in the tumor and decreased levels in the gut (194).
  • Muscle glycogenMuscle glycogen: In human research, glutamine supplementation promoted storage of muscle glycogen following exercise, to a similar extent as oral glucose polymer (36). Glutamine had no effect on muscle glycogen in other studies (195).
  • Nitrogen balanceNitrogen balance: Glutamine had protein-sparing or improved-nitrogen-balance effects in infants, and nonhealthy children and adults (153; 154; 155; 156; 103; 3; 18; 105; 1; 118; 157; 8; 7; 107). In human research, glutamine supplementation decreased urinary nitrogen and urinary 3-methylhistidine (11; 71). In human research, glutamine had no effect on urinary nitrogen or nitrogen balance (196).
  • ProteinsProteins: In human research, glutamine has been shown to increase levels of albumin, prealbumin, and transferrin (23; 11; 58; 71). Other studies in humans found that glutamine had a lack of an effect on serum protein levels (196).
  • TemperatureTemperature: In human research, glutamine reduced body temperature (130).
  • Urinary ammoniumUrinary ammonium: Urinary ammonium increased in glutamine supplemented healthy individuals, but not patients with renal disease (44).
  • Urinary lactulose:mannitol (L:M) ratioUrinary lactulose:mannitol (L:M) ratio: In human research, glutamine supplementation decreased the urinary lactulose:mannitol ratio (130).
  • White blood cell countWhite blood cell count: In human research, glutamine reduced levels of white blood cells (130). In human research, glutamine supplementation increased lymphocyte count, with an increase in CD3+, CD4+, and CD8+, and normalization of the CD16+CD56+ subset (14; 23; 3; 24; 197).