L-Glutamine for Leaky Gut and IBS: What the Trials Show (One Striking Trial, Little Else)
Glutamine helps maintain the gut lining, which is why it headlines 'leaky gut' protocols. One US trial in post-infection IBS was dramatic; pooled trials on gut permeability were flat, and in intensive care high doses did harm.
By Kymata Health Editorial Published Last checked
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Momentous L-Glutamine, 60 servings
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Key takeaways
From 5 sources- The headline trial analysed 106 adults whose diarrhoea-type IBS began after a gut infection and who had measurably high gut permeability: 5 g three times a day for 8 weeks cut symptom scores by at least 50 points in 79.6% versus 5.8% on placebo1.
- That result comes from one US trial in a narrowly defined group, and its authors called for large randomized trials to confirm it1.
- Across 10 randomized trials (352 participants) in mixed patient groups, glutamine did not significantly change intestinal permeability overall2.
- In active Crohn's disease, a Cochrane review found only two small trials (42 patients), with no change in permeability and too little evidence to draw conclusions3.
- In ventilated intensive-care patients, high-dose intravenous plus enteral glutamine was linked to significantly higher in-hospital and 6-month mortality, with a non-significant trend at 28 days (32.4% vs 27.2%)4.
What this article covers
1 evidence profileThe evidence, graded
Pulled from the trial tables in our evidence profiles. Grades follow our evidence-grading policy.
Graded findings
1 row- CGrade C28-day mortality in critical illnessWorsened 28-day mortality trended higher with glutamine (32.4% vs 27.2%), and in-hospital and 6-month mortality were significantly higher.L-glutamine · RCT · n=1,223 · 2013 · PMID 23594003
What 'leaky gut' means in a trial
'Leaky gut' is a popular label, but trials measure something narrower: intestinal permeability, for example with the urinary lactulose-to-mannitol sugar test, where a higher ratio means a more permeable gut lining1.
Glutamine plays a key role in maintaining the intestinal lining, which is the rationale for trying it3. The question is whether swallowing extra glutamine changes permeability or symptoms in people who are not critically ill2.
The IBS trial everyone cites
In a randomized, double-blind trial at a US centre, adults who developed diarrhoea-predominant IBS after an enteric infection, and who had high permeability on testing, took 5 g of glutamine three times daily or a whey-protein placebo for 8 weeks1.
Of 54 people on glutamine and 52 on placebo who finished, 43 (79.6%) versus 3 (5.8%) reached the main goal of a 50-point drop on the IBS severity score1. Bowel-movement frequency, stool form and permeability also improved, and adverse events were low and similar in both groups1.
The authors themselves called for large randomized trials to validate the finding and explore how it works1. For an IBS option with a deeper trial base, see peppermint oil for IBS.
Pooled trials on gut permeability
A 2024 meta-analysis gathered 10 randomized placebo-controlled trials published between 1998 and 2014 (352 participants, mean age 46.5) and found no significant overall effect of oral glutamine on intestinal permeability2. A subgroup on very high doses for short periods showed a reduction, but the abstract reports the threshold inconsistently, so we do not lean on it2.
In active Crohn's disease, the Cochrane review found two small trials totalling 42 patients; neither showed a significant change in permeability, and remission was 44% with a glutamine-enriched diet versus 56% with a standard diet in the paediatric trial3.
The intensive-care warning
The REDOXS trial randomized 1,223 critically ill adults with multiorgan failure on mechanical ventilation in 40 intensive care units to glutamine, antioxidants, both or placebo, given intravenously and through a feeding tube4. Mortality at 28 days trended higher with glutamine (32.4% vs 27.2%), and in-hospital and 6-month mortality were significantly higher4.
These were very sick patients on far larger doses than a supplement scoop, but the trial ended the assumption that more glutamine is always harmless4. Our L-glutamine page grades this and the sickle cell evidence.
Who paid for the research
The IBS trial was supported by NIH grants from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Complementary and Integrative Health and the National Institute of General Medical Sciences, and its authors declared no competing interests1.
REDOXS was funded by the Canadian Institutes of Health Research; Fresenius Kabi, which makes intravenous glutamine, provided the glutamine supplements and an unrestricted grant, with no decision-making role4. The 2024 meta-analysis authors declared no conflicts2.
Who should be careful
Drug interactions: Memorial Sloan Kettering's integrative medicine service notes that glutamine may reduce the ammonia-lowering effect of lactulose used for hepatic encephalopathy (not when lactulose is used as a laxative), and that glutamine may interact with methotrexate5. That matters for people with cirrhosis whose ammonia is managed with lactulose5. Check other medicines in the interaction checker.
Other cautions: the same source describes a case of liver injury after 3 weeks of glutamine powder and a case of acute kidney injury after long-term use of 18 g a day5. Critically ill patients are the group in which harm was shown4. The prescription L-glutamine used in sickle cell disease is a separately regulated product dosed by a clinician.
Quick answers
Common questions
4 answersDoes L-glutamine help leaky gut?
How much L-glutamine was used in the IBS trial?
5 g three times a day for 8 weeks, in adults with post-infection, diarrhoea-predominant IBS1.
Does L-glutamine help Crohn's disease or colitis?
A Cochrane review found only two small trials in active Crohn's, with no permeability benefit and insufficient evidence to judge remission3.
Keep reading
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3 products Paid links · we earn a commission- Quick pickMomentousMomentous L-Glutamine, 60 servingsWe use this brand at home. What we useSubscribe & save 25%
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1 scoop (5 g): 5 g L-glutamine; 60 servings
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1 serving: 3 g L-glutamine powder; 50 servings
$21.00one-time$17.85subscribeChecked Oct 11, 2026 - HerbsProNOW Foods L-Glutamine, 1000 mg, 120 Caps
1 capsule: 1,000 mg free-form L-glutamine; label directions 1 capsule 1 to 3 times daily
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References
5 sources. Numbers in the text link here.
Sources cited in this article
5 sources- 1Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndromeGut, 2019 · PMID 30108163
- 2A systematic review and meta-analysis of clinical trials on the effects of glutamine supplementation on gut permeability in adultsAmino Acids, 2024 · PMID 39397201
- 3Glutamine for induction of remission in Crohn's diseaseCochrane Database of Systematic Reviews, 2016 · PMID 26853855
- 4A randomized trial of glutamine and antioxidants in critically ill patients (REDOXS)New England Journal of Medicine, 2013 · PMID 23594003
- 5Glutamine (About Herbs; accessed October 14, 2026)Memorial Sloan Kettering Cancer Center, 2026
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