Does glutamine help with Irritable Bowel Syndrome (IBS)?

Glutamine for Irritable Bowel Syndrome (IBS)

Glutamine supplementation may be beneficial for IBS, particularly in post-infectious IBS with intestinal hyperpermeability, but it is not currently recommended as a first-line treatment in major clinical guidelines.

Evidence for Glutamine in IBS

Strongest Evidence

• A randomized, double-blind, placebo-controlled trial showed that glutamine (5g three times daily) dramatically reduced IBS symptoms in patients with post-infectious IBS-D with intestinal hyperpermeability 1
• This study demonstrated a 14-fold difference in achieving significant symptom reduction compared to placebo
• Glutamine normalized intestinal hyperpermeability in these patients
• Another randomized controlled trial found that adding glutamine (15g/day) to a low FODMAP diet was superior to low FODMAP diet alone, with 88% of participants in the glutamine group achieving >45% improvement in IBS severity scores versus 60% in the control group 2

Mechanism of Action

• Glutamine appears to work by repairing intestinal barrier function in patients with increased intestinal permeability
• This is particularly relevant for post-infectious IBS where barrier dysfunction is a key pathophysiological feature

Current Guideline Recommendations for IBS Management

The British Society of Gastroenterology (2021) and American Gastroenterological Association guidelines do not specifically mention glutamine for IBS treatment, instead recommending 3:

First-line treatments:

• Regular exercise (strong recommendation, weak evidence)
• Dietary modifications (strong recommendation, weak evidence)
• Soluble fiber like ispaghula (strong recommendation, moderate evidence)
• Low FODMAP diet as second-line dietary therapy (weak recommendation, very low evidence)
• Probiotics (weak recommendation, very low evidence)
• Loperamide for IBS-D (strong recommendation, very low evidence)
• Antispasmodics (weak recommendation, very low evidence)

Second-line treatments:

• Tricyclic antidepressants as gut-brain neuromodulators (strong recommendation, moderate evidence)
• Selective serotonin reuptake inhibitors (weak recommendation, low evidence)

Clinical Application Algorithm

1. Identify suitable candidates for glutamine therapy:

   • Patients with post-infectious IBS-D
   • Patients with suspected intestinal hyperpermeability
   • Patients who have failed first-line treatments

2. Dosing recommendations based on evidence:

   • 5g three times daily (15g total daily dose) 1
   • Consider combining with low FODMAP diet for potentially enhanced effects 2

3. Monitoring:

   • Assess improvement in IBS symptoms after 8 weeks
   • Monitor for adverse effects (generally minimal based on clinical trials)

Important Considerations

• Glutamine supplementation appears safe with minimal adverse effects reported in clinical trials
• The strongest evidence exists for post-infectious IBS-D with intestinal hyperpermeability
• Effects in other IBS subtypes are less well-established
• Glutamine may be more effective when combined with other evidence-based approaches like the low FODMAP diet

Limitations and Caveats

• Current major guidelines do not yet include glutamine as a recommended treatment
• More large-scale randomized clinical trials are needed to validate these findings
• Long-term effects of glutamine supplementation are not well-established
• Cost-effectiveness compared to other IBS treatments has not been determined

While promising, glutamine should be considered as an adjunctive therapy rather than replacing established first-line treatments for IBS until more definitive evidence and guideline recommendations emerge.