L-Glutamine


Clinical Studies


Glutamine is used for depression, irritability, anxiety, insomnia and gastro-intestinal disorders. It is also used for attention deficit-hyperactivity disorder (ADHD) and for alcohol, smoking and drug withdrawal support. Although classified as a non-essential amino acid, Glutamine is essential for maintaining intestinal function, immune response and amino acid balance in the body during times of severe stress. Glutamine can enhance the function of stimulated immune cells. Some research suggests that in patients with cancer it might restore natural killer cell function in healthy cells and improve protein metabolism. Glutamine treatment is thought to help prevent chemotherapy and radiation-induced gastrointestinal toxicity. Some preliminary evidence suggests that Glutamine might protect the heart from ischemia in patients with chronic stable angina. Glutamine may have a neuro-protective action.

Published Clinical Studies
L-Glutamine

The role of dietary supplementation with L-glutamine in inflammatory mediator release and intestinal injury in hypoxia/reoxygenation-induced experimental necrotizing enterocolitis.

Akisu M, Baka M, Huseyinov A, Kultursay N.

Department of Pediatrics, Ege University Medical School, Bornova, TR-35100 Izmir, Turkey. makisu@med.ege.edu.tr

BACKGROUND/AIMS: Necrotizing enterocolitis (NEC) is a multifactorial syndrome in the neonate. Enteral feeding practices are an important component of gastrointestinal injury in neonatal NEC. In the present study, we examined the protective effect of oral supplementation with L-glutamine, an important specific fuel for the enterocytes, against hypoxia-reoxygenation (H/R)-induced NEC in young mice. METHODS: Young mice were divided into four groups: group 1 mice (untreated) underwent H/R; group 2 mice were supplemented with L-glutamine in drinking water (0.5 g/dl) for 3 days, and group 3 mice were supplemented with L-glutamine (3 g/dl) for 10 days. Group 4 mice served as control. Hypoxia was induced by placing the young mice in a 100% CO(2) chamber for 5 min. After hypoxia, they were reoxygenated for 10 min with 100% oxygen. We examined the intestinal lesions with light microscopy and measured intestinal generation of PAF and TNF-alpha in the H/R-induced model of NEC. RESULTS: In group 3 mice, NEC-induced intestinal tissue damage was greatly attenuated with necrosis limited partially to the mucosa. Both intestinal tissue PAF and TNF-alpha concentrations were significantly higher in the untreated group than in controls (p < 0.001). Group 3 mice (3 g/dl supplemented) showed a significant decrease in intestinal TNF-alpha concentration compared with young group 1 and group 2 mice (p < 0.05 and p < 0.05, respectively). On the other hand, no significant difference was observed in the intestinal generation of PAF between H/R groups (p > 0.05). CONCLUSION: The present study suggests that H/R plays an important role in the pathogenesis of NEC and supports the hypothesis that especially PAF and TNF-alpha are involved in the pathophysiological mechanism of H/R-induced NEC. This study also demonstrates that dietary supplementation with L-glutamine reduces the histologic evidence of H/R-induced intestinal injury. Based on these findings, beneficial effects of L-glutamine in this model of NEC are mediated via mechanisms inhibiting intestinal cytokine release. Copyright 2003 S. Karger AG, Basel.

PMID: 14520021 [PubMed - in process]

back



[Protective effect of glutamine on microcirculation of the intestine in experimental colitis]

Kruschewski M, Perez-Canto S, Hubotter A, Foitzik T, Buhr HJ.

Chirurgische Klinik I, Universitatsklinikum Benjamin Franklin, Freie Universitat Berlin, Berlin.

Parenteral glutamine application can stabilize intestinal permeability and mucosal integrity. It is not known whether glutamine influences the microcirculation in the large intestine. This study thus employs intravital microscopy to investigate mucosal microcirculation in the ascending and descending Colon of Sprague-Dawley rats with TNBS colitis. The animals were randomized and treated with either saline solution (placebo) or glutamine (verum). In the severely inflamed descending colon, TNBS colitis involves a significant capillary blood flow reduction that is not improved by glutamine application. Though the ascending colon shows only a mild inflammatory reaction, its microcirculation is likewise significantly reduced. Here glutamine therapy is associated with an increase in capillary blood flow, indicating that it has a protective effect on the microcirculation of the secondarily involved intestinal segment.

PMID: 14518249 [PubMed - indexed for MEDLINE]

back



Timing of oral glutamine on DMBA-induced tumorgenesis.

Kaufmann Y, Luo S, Johnson A, Babb K, Klimberg VS.

Department of Surgery, Division of Surgical Oncology, University of Arkansas for Medical Sciences, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA.

INTRODUCTION: A single dose of oral 7,12-dimethylbenz(a)anthracene (DMBA) in pubertal rats causes breast tumors by 11 weeks and is associated with ablation of the normal gut glutathione (GSH) production for up to 4 weeks. We hypothesized that glutamine (GLN), known to restore the gut GSH production inhibited by DMBA, given only during this 4-week period, would prevent breast cancer initiation. METHODS: 160 Female Sprague-Dawley rats were divided to 10 groups (n = 16/group): Long Term (LT): DMBA + GLN, DMBA + FA, DMBA + H2O, OIL + GLN, OIL + FA, OIL + H2O; Short Term (ST): DMBA + GLN, DMBA + FA, OIL + GLN, OIL + FA At age 50 days old, rats received a one-time dose of 100 mg/kg DMBA or sesame oil. LT rats were gavaged daily with isonitrogenous GLN, (FA), or water (H2O) the entire study. ST rats were gavaged with GLN, freamine, or H2O the first 4 weeks and then H2O the remaining 7 weeks. All rats were pair-fed defined chow. Rats were sacrificed at 11 weeks, observed for tumors, blood assayed for GLN, GSH, gut GLN and GSH and uptake or production calculated using labeled C-14-PAH. RESULTS: ST and LT GLN were equally effective in preventing tumor formation. GLN doubled gut GSH production in LT animals as compared to all other groups (P < 0.05). Control rats developed no tumors and had superior gut GSH production as compared with tumor-bearing rats. CONCLUSIONS: Oral GLN when given only during the 4 weeks of known gut GSH ablation had the same tumor prevention efficacy as prolonged GLN administration. Not previously reported, GLN appears to affect the initiation of tumor formation in this model.

PMID: 12842461 [PubMed - indexed for MEDLINE]

back



Psychic dependence? A different formulation of the problem with a view to the reorientation of therapy for chronic drug addiction.

Cocchi R, Tornati A.

Disputing the concept of "psychic dependence", the authors review six motivations to use addictive drugs, four of which pertain to the moment of assumption of the habit, and two of which, identifiable with physical and psychic dependence, depend on breaking of the habit. While physical dependence is linked to withdrawal syndrome, psychic dependence, in the authors' opinion, is related to a longstanding previous state of true of masked endogenous depression (in this case it would be well termed "neuropsychological dependence"), and the drug taking is only a maladaptive self-medication. This thesis is substantiated by the literature reporting, in chronic drug addicts, the use of the whole series of antidepressants (i.e. tricyclics, doxepine, lithium, etc.) with noticeable therapeutical success. In accordance with other reports and with personal experience, the authors assign great importance to the drugs acting, directly or indirectly, on GABA, i.e. L-glutamine, piracetam, and, particularly, N-dipropylacetic acid.

PMID: 22989 [PubMed - indexed for MEDLINE]

back



Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study.

Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F.

Max Planck Institute of Psychiatry, Munich, Germany.

BACKGROUND: Functional imaging studies suggest a specific role of the anterior brain regions in the pathogenesis of major depression. The aim of this study was to evaluate possible neurochemical alterations in the frontomesial cortex in patients with major depressive episode using in vivo proton magnetic resonance spectroscopy ((1)H-MRS). METHODS: Single voxel (1)H-MRS was performed in 19 patients with major depressive episodes and 18 age-matched healthy controls within the anterior cingulate cortex and the parietal white matter. Absolute concentrations were estimated for N-acetyl-aspartate, choline-containing compounds, total creatine, myo-inositol, unresolved glutamate and glutamine (Glx) and glutamate alone (Glu). Voxel composition was analyzed by image segmentation into cerebrospinal fluid (CSF), grey and white matter. RESULTS: MANOVA test for Glx and Glu using age, percent CSF and percent grey matter contribution as covariates yielded a significant group effect within the anterior cingulate due to decrease of Glx in patients (-10.4%, p =.013). Considering only severely depressed patients, both Glx and Glu (-14.3%, p =.03) showed a significant decrease. There was no significant group effect for the neuronal marker NAA, creatine, choline or myo-inositol in either localization. CONCLUSIONS: This study suggests a possible role of altered glutamatergic neurotransmission within the anterior cingulate in the pathogenesis of mood disorders. The otherwise unremarkable findings of major brain metabolites confirms lack of neurodegenerative or membrane metabolic changes in major depression.

PMID: 10686265 [PubMed - indexed for MEDLINE]