Anthony K Akobeng, Mamoun Elawad, Morris Gordon

Crohn's disease is a chronic relapsing condition of the alimentary tract with a high morbidity secondary to bowel inflammation. Glutamine plays a key role in maintaining the integrity of the intestinal mucosa and has been shown to reduce inflammation and disease activity in experimental models of Crohn's disease. To evaluate the efficacy and safety of glutamine supplementation for induction of remission in Crohn's disease. We searched the following databases from inception to November 15, 2015: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane IBD Group Specialised Register. Study references were also searched for additional trials. There were no language restrictions. Randomised controlled trials (RCTs) that compared glutamine supplementation administered by any route to a placebo, active comparator or no intervention in people with active Crohn's disease were considered for inclusion. Two authors independently extracted data and assessed the methodological quality of the included studies. The Cochrane risk of bias tool was used to assess methodological quality. The primary outcome measure was clinical or endoscopic remission. Secondary outcomes included intestinal permeability, clinical response, quality of life, growth in children and adverse events. Risk ratios and 95% confidence intervals were calculated for dichotomous outcomes. The overall quality of the evidence supporting the primary outcome was evaluated using the GRADE criteria. Two small RCTs (total 42 patients) met the inclusion criteria and were included in the review. One study (18 patients) compared four weeks of treatment with a glutamine-enriched polymeric diet (42% amino acid composition) to a standard polymeric diet (4% amino acid composition) with low glutamine content in paediatric patients (< 18 years of age) with active Crohn's disease. The other study (24 patients) compared glutamine-supplemented total parenteral nutrition to non-supplemented total parenteral nutrition in adult patients (> 18 years of age) with acute exacerbation of inflammatory bowel disease. The paediatric study was rated as low risk of bias. The study in adult patients was rated as unclear risk of bias for blinding and low risk of bias for all other items. It was not possible to pool data for meta-analysis because of significant differences in study populations, nature of interventions, and the way outcomes were assessed. Data from one study showed no statistically significant difference in clinical remission rates at four weeks. Forty-four per cent (4/9) of patients who received a glutamine-enriched polymeric diet achieved remission compared to 56% (5/9) of patients who received a standard low-glutamine polymeric diet (RR 0.80, 95% CI 0.31 to 2.04). A GRADE analysis indicated that the overall quality of evidence for this outcome was low due to serious imprecision (9 events). In both included studies, no statistically significant changes in intestinal permeability were found between patients who received glutamine supplementation and those who did not. Neither study reported on clinical response, quality of life or growth in children. Adverse event data were not well documented. There were no serious adverse events in the paediatric study. The study in adult patients reported three central catheter infections with positive blood cultures in the glutamine group compared to none in the control group (RR 7.00, 95% CI 0.40 to 122.44). Currently there is insufficient evidence to allow firm conclusions regarding the efficacy and safety of glutamine for induction of remission in Crohn's disease. Data from two small studies suggest that glutamine supplementation may not be beneficial in active Crohn's disease but these results need to be interpreted with caution as they are based on small numbers of patients. This review highlights the need for adequately powered randomised controlled trials to investigate the efficacy and safety of glutamine for induction of remission in Crohn's disease.