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

Gut. 2019 Jun;68(6):996-1002. doi: 10.1136/gutjnl-2017-315136. Epub 2018 Aug 14.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Enteritis / complications
  • Enteritis / microbiology*
  • Female
  • Glutamine / therapeutic use*
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / microbiology
  • Irritable Bowel Syndrome / diagnosis
  • Irritable Bowel Syndrome / drug therapy*
  • Irritable Bowel Syndrome / microbiology
  • Male
  • Reference Values
  • Risk Assessment
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Glutamine

Associated data

  • ClinicalTrials.gov/NCT01414244