Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome
Open accessAbstract
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.
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Modest increases in zinc intake (9.2-25 mg/day) over longer durations (≥12 weeks) were associated with improvements in insulin resistance, fasting glycemia, LDL-c, total cholesterol, and triglycerides in healthy and metabolically impaired populations.
“Similarly, a meta-analysis reported that modest increases in zinc intake (9.2-25 mg/day) over longer durations (≥12 weeks) were associated with improvements in insulin resistance, fasting glycemia, LDL-c, total cholesterol, and triglycerides, both in healthy and metabolically impaired populations [181].”
From Nutritional Approaches to Enhance GLP-1 Analogue Therapy in Obesity: A Narrative Review (2025) · cites this paper as [181]
Zinc plays a role in lipid metabolism through antioxidant, anti-inflammatory, and other mechanisms that may modulate atherosclerosis and cardiovascular disease risk.
“Zinc also plays a role in lipid metabolism through antioxidant, anti-inflammatory, and other mechanisms that may modulate atherosclerosis and cardiovascular disease (CVD) risk [181].”
From Nutritional Approaches to Enhance GLP-1 Analogue Therapy in Obesity: A Narrative Review (2025) · cites this paper as [181]
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- Authors
- Zhou, Q., Verne, M. L., Fields, J. Z., Lefante, J. J., Basra, S., Salameh, H., & Verne, G. N.
- Affiliations
- Tulane University (US)
- Texas A&M Health Science Center (US)
- The University of Texas Medical Branch at Galveston (US)
- Corresponding author
- Verne, G Nicholas
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2018-08-14
- Volume
- 68
- Issue
- 6
- Pages
- 996-1002
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC9549483
- OpenAlex
- W2888929155
- Cited by
- 195
- References
- 40
- Citations by year
- 2026: 21 · 2025: 30 · 2024: 26 · 2023: 22 · 2022: 21 · 2021: 26 · 2020: 31 · 2019: 13 · 2018: 5
- FWCI
- 17.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institute of General Medical Sciences
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Center for Complementary and Integrative Health
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- dietary glutamine, post-infectious irritable bowel syndrome, diarrhoea-predominant IBS, intestinal permeability, leaky gut, gastrointestinal infections, lactulose/mannitol ratio, IBS symptom severity, stool frequency, stool consistency, oral supplementation
- MeSH terms
- Administration, Oral, Adult, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Enteritis, Female, Glutamine, Humans, Intestinal Mucosa, Male, Reference Values, Severity of Illness Index, Treatment Outcome, Risk Assessment, Dietary Supplements, Irritable Bowel Syndrome
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