Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome

Abstract

Background: More effective treatments are needed for patients with postinfectious, diarrhoea-predominant, irritable bowel syndrome (IBS-D). Accordingly, we conducted a randomised, double-blind, placebo-controlled, 8-week-long trial to assess the efficacy and safety of oral glutamine therapy in patients who developed IBS-D with increased intestinal permeability following an enteric infection.

Methods: Eligible adults were randomised to glutamine (5 g/t.i.d.) or placebo for 8 weeks. The primary end point was a reduction of ≥50 points on the Irritable Bowel Syndrome Severity Scoring System (IBS-SS). Secondary endpoints included: raw IBS-SS scores, changes in daily bowel movement frequency, stool form (Bristol Stool Scale) and intestinal permeability.

Results: Fifty-four glutamine and 52 placebo subjects completed the 8-week study. The primary endpoint occurred in 43 (79.6%) in the glutamine group and 3 (5.8%) in the placebo group (a 14-fold difference). Glutamine also reduced all secondary endpoint means: IBS-SS score at 8 weeks (301 vs 181, p<0.0001), daily bowel movement frequency (5.4 vs 2.9±1.0, p<0.0001), Bristol Stool Scale (6.5 vs 3.9, p<0.0001) and intestinal permeability (0.11 vs 0.05; p<0.0001). 'Intestinal hyperpermeability' (elevated urinary lactulose/mannitol ratios) was normalised in the glutamine but not the control group. Adverse events and rates of study-drug discontinuation were low and similar in the two groups. No serious adverse events were observed.

Conclusions: In patients with IBS-D with intestinal hyperpermeability following an enteric infection, oral dietary glutamine supplements dramatically and safely reduced all major IBS-related endpoints. Large randomised clinical trials (RCTs) should now be done to validate these findings, assess quality of life benefits and explore pharmacological mechanisms.

Trial registration number: NCT01414244; Results.

Keywords: diarrhoea; enteric infections; intestinal permeability; irritable bowel syndrome.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1.

Patient enrollment, randomization, and retention

Figure 2.

Plot of Δ IBS-SS vs. Δ Intestnal Permeability in response to Glutamine treatment vs. Placebo treatment

Figure 3.

5 Components of the IBS-SS following glutamine therapy compared to placebo: Figure 3A. Abdominal distension and bloating; Figure 3B. Abdominal pain frequency; Figure 3C. Abdominal pain severity; Figure 3D. Quality of life; Figure 3E. Satisfaction with bowel habits.