L-glutamine

L-glutamine is the most abundant amino acid in the body and a fuel for the cells lining the small intestine. The rationale for testing it in IBS comes from a subgroup of patients whose symptoms began after a gut infection and who show increased intestinal permeability on lactulose-mannitol testing; the hypothesis is that supplemental glutamine may help the intestinal barrier recover, which in turn may reduce diarrhoea and pain PMID 30108163. It is sold as a powder or capsule supplement, mostly marketed to athletes, and is not a prescription product.

The evidence is one trial. Investigators in the United States randomised adults with diarrhoea-predominant IBS that developed after an enteric infection, all with documented intestinal hyperpermeability, to 5 g of glutamine three times a day or placebo for eight weeks. Among the 54 glutamine and 52 placebo participants who completed the study, the primary endpoint, a reduction of at least 50 points on the IBS Severity Scoring System, was met by 79.6% on glutamine and 5.8% on placebo. Mean severity score at eight weeks was 181 with glutamine versus 301 with placebo, daily bowel movements were 2.9 versus 5.4, stool form on the Bristol scale was 3.9 versus 6.5, and the permeability ratio normalised in the glutamine group but not the control group. Adverse events and discontinuations were low and similar in both arms, with no serious adverse events PMID 30108163.

Those numbers invite caution as much as interest. A 5.8% placebo response is far below what IBS trials usually see, and a 14-fold difference between arms is larger than any established IBS therapy produces; the authors themselves wrote that large randomised trials should now be done to validate the findings. The trial enrolled a narrowly defined group, post-infectious IBS-D with measured hyperpermeability, so the result says nothing about IBS-C, IBS-M, or the majority of people with IBS-D whose symptoms did not follow an infection. Permeability testing of the kind used to select participants is not part of routine care.

Points clinicians commonly raise: 15 g per day is a substantial dose, well above what is found in food, and the trial ran for only eight weeks; glutamine is generally regarded as safe in healthy adults but is metabolised by the liver and kidneys, so people with liver or kidney disease should ask before using it; and because the evidence rests on a single unreplicated study, a positive result in one person is as likely to reflect the natural fluctuation of IBS as the supplement.

Talk to a clinician before starting or stopping anything.