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Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome
  1. QiQi Zhou1,2,
  2. Meghan L Verne3,
  3. Jeremy Z Fields1,
  4. John J Lefante4,
  5. Sarpreet Basra1,
  6. Habeeb Salameh5,
  7. G Nicholas Verne1
  1. 1 Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA
  2. 2 Department of Veteran Affairs, Malcom Randall VAMC, Gainesville, Florida, USA
  3. 3 Health Sciences, Texas A&M University, College Station, Texas, USA
  4. 4 Department of Global Biostatistics and Data Science, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA
  5. 5 Department of Medicine, University of Texas Medical Branch, Galveston, Texas, USA
  1. Correspondence to Dr G Nicholas Verne, Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112-2699, USA; gverne{at}


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 NCT1414244; Results.

  • irritable bowel syndrome
  • diarrhoea
  • enteric infections
  • intestinal permeability

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  • Contributors All authors contributed to the design and draft of the paper.

  • Funding This study was supported by the National Center for Complementary and Integrative Health (AT005291); National Institute of Diabetes and Digestive and Kidney Diseases (DK099052) and the Department of Veterans Affairs (CX001477-01). Supported in part by 1 U54 GM104940 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. number, NCT1414244.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.