Gut Repair

Preliminary research on enteral (as well as parenteral) glutamine supplementation suggests promise for the use of glutamine in gut repair by: (i) protecting the intestinal mucosa from damage and promoting repair, thus improving intestinal permeability and reducing subsequent microbial and endotoxin translocation, promoting glutathione and S-lgA, and (ii) improving gut immunity. However, while there is considerable evidence for the use of glutamine in TPN (Hall et al 1996), clinical evidence using oral supplementation is less convincing. As in vitro data suggests that the colonic mucosa receives its nutrients preferentially from the luminal (not vascular) side (Roediger 1986) it has been suggested that glutamine may be more effective when delivered by the enteral route (Kouznetsova et al 1999). This has yet to be determined in clinical trials.

In a 1998 randomised, double-blind, placebo-controlled, 4-week trial of 24 HIV patients with abnormal intestinal permeability using 0, 4 or 8 g/day of glutamine, the authors reported a dose-dependent trend towards improved intestinal permeability and enhanced intestinal absorption with glutamine supplementation and recommended further studies to be carried out with higher doses (e.g. 20 g/day) over a longer study period (Noyer et al 1998). It is difficult to extrapolate the findings of this study to the wider community for the purpose of gut repair as there are factors involved in HIV/AIDS that may increase the biological demand for glutamine.

L-glutamine enemas, twice daily for 7 days, have been shown to reduce mucosal damage and inflammation in experimental models of colitis in rats (Kaya et al 1999); however, preliminary trials in humans have not confirmed benefit. A 4-week study on 18 children with active Crohn's disease fed a glutamine-enriched polymeric diet (Akobeng et al 2000) and another 4-week study on 14 patients taking 7 g glutamine three times daily (Hond et al 1999a) showed similarly negative results. Longer term studies may provide more convincing results; however, it is possible that glutamine only stabilises gut barrier function under certain conditions and more research is required to elucidate these.

l-glutamine has been shown to improve glutathione levels and significantly increase lean body mass in HIV patients (Patrick 2000); however, not all studies confirm this latter effect (Huffman & Walgren 2003). Combined therapy with arginine and the L-Glutamine 616

leucine metabolite beta-hydroxy-beta-methylbutyrate has been shown to reverse lean tissue loss in HIV and cancer patients (Rathmacher et al 2004).

During initial HIV infection, the rapid turnover and proliferation of immune cells increases glutamine requirements and later the repeated episodes of infection, fever and diarrhoea may lead to further depletion. As a result the doses used in the trial mentioned above (4 g and 8 g) may have been insufficient to meet the increased requirement in such patients (Noyer et al 1998).

Highly active antiretroviral therapy may be associated with diarrhoea and other gastrointestinal side-effects. In a prospective, randomised, double-blind, crossover study, HIV-infected patients with nelfinavir-associated diarrhoea (for >1 month) received L-GIn (30 g/day) or placebo for 10 days. Glutamine supplementation resulted in a significant reduction in the severity of nelfinavir-associated diarrhoea (Huffman & Walgren 2003). A prospective 12-week trial of 35 HIV-positive men experiencing diarrhoea as a result of nelf inavir or lopinavir/ritonavir therapy was also conducted using probiotics and soluble fibre. When glutamine (30 g/day) was added to the regimen of non-responders at week 4, the response rate improved (Heiser et al 2004).

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