Reference: Gut. 2019 Jun;68(6):996-1002 (level 2 [mid-level] evidence)Oral glutamine may reduce IBS symptoms in adults with post-infectious IBS with diarrhea predominance
Irritable bowel syndrome (IBS) is a fairly common disorder affecting about 14% of women and 8.9% of men worldwide Clin Gastroenterol Hepatol. 2012 Jul. The most prevalent symptoms include chronic abdominal pain and a change in normal bowel habits on a spectrum from constipation to diarrhea. Many factors are associated with development of IBS with several proposed mechanisms, but the specific etiology has not been determined. In a meta-analysis of infectious gastroenteritis studies, it was estimated that about 18% went on to develop IBS N Engl J Med. 2017 Jun 29. Given the high burden of symptoms and limited treatment options new effective therapies are required.
This randomized double-blind placebo-controlled trial evaluated whether supplementation with glutamine improved diarrhea and IBS symptoms in those suffering from post-infectious IBS with diarrhea predominance Gut. 2019 Jun. 115 adults (aged 18-72) who met Rome III criteria for IBS (diarrhea predominant), had an enteric infection documented in their record at least 1 year prior to enrollment, and had increased intestinal permeability (urinary lactulose/mannitol ratio ≥ 0.07) were included . Patients with bacterial overgrowth, inflammatory bowel disease, celiac disease or positive tTG IgA antibody, low or abnormal immunoglobulins, liver disease or impaired liver function, renal disease, or pancreatitis were excluded. Additionally, patients who consumed alcohol or NSAIDs two weeks prior to the study, patients with known allergies to glutamine/whey protein, those who were breastfeeding or pregnant, or were taking glutamine supplements or had diets high in glutamine were also excluded. Patients were randomized to 5g glutamine or placebo (whey protein) 3 times daily orally for 8 weeks. The primary outcome was a ≥ 50 point-reduction on the Irritable Bowel Syndrome Severity Score System (IBS-SS, range 0-500 points with higher score indicating greater symptom severity). Secondary outcomes included raw IBS-SS score, daily stool frequency, stool consistency (Bristol stool scale), and intestinal permeability. Outcomes were assessed at the beginning of the 8-week period and again at the conclusion of the study. 92% of adults completed the study and were included in analysis.
The primary outcome occurred in 79.6% of adults receiving glutamine and in 5.8% of adults receiving placebo (p < 0.0001, NNT 2). Mean reduction in stool frequency was 2.5 episodes daily in glutamine group, compared to 0.05 episodes daily in placebo group (p <0.0001). Mean change in stool consistency (on Bristol stool scale) was -2.64 (improvement) in glutamine group, compared to 0.02 in the placebo group (p < 0.0001). Mean improvement in intestinal permeability (lactulose/mannitol ratio) was 0.06 in the glutamine group compared to 0.0004 in the placebo group (p < 0.0001). Adverse events occurred in 3.8% in both groups.
There are some limitations to this study. Though the drop out rate was similar in both groups, this study did not use an intention to treat analysis and did not comment on the frequency of commonly used anti-diarrhea agents, anti-spasmotic agents, and SSRIs, all of which are frequently prescribed to manage IBS symptoms. Additionally, this is a small study only examining post infection IBS and more research should be conducted in a larger population to compare different lengths of treatment.
Given the limitations of this study, supplementation with oral glutamine 5 g taken 3 times daily may improve symptom severity at 8 weeks in patients with diarrhea-predominant IBS following an enteric infection. Given the lack of other effective treatments, glutamine could offer some relief for a common and difficult to treat problem.
For more information, see the topic Irritable Bowel Syndrome (IBS) in DynaMed.
April Kavanagh, MD, MPH
April is a faculty development fellow in the Department of Family Medicine at the University of Virginia. She has an interest in preventive health, especially for cancer survivors, and is helping to establish a specialty cancer survivorship clinic at UVA.