September 2018 Hot Topic: Glutamine & Gastrointestinal Diseases

Man on couch with stomach pain

Can glutamine supplementation help patients with irritable bowel syndrome (IBS) and IBS-D (diarrhea-predominant IBS)? If so, what form of glutamine would be most beneficial?

Functional Medicine practitioners have long recognized the gut-healing powers of glutamine, and recent research is bearing this out. In August 2018, Gut published the results of a randomized placebo-controlled trial of dietary glutamine supplements for post-infectious irritable bowel syndrome, with clinically significant findings.1 The study suggests that in patients with IBS-D and intestinal hyperpermeability following an enteric infection, oral dietary glutamine supplements dramatically and safely reduced all major IBS-related end points. This included a reduction of >50 points on the Irritable Bowel Syndrome Severity Scoring System and changes in daily bowel movement frequency, stool form, and intestinal permeability.1

Glutamate is an amino acid used for several things in the body, including as a neurotransmitter, and it plays a vital role in maintaining and repairing gut barrier function.2 In the past, it was assumed by the medical community that glutamine was a “nonessential amino acid” and was not required in the diet because the body has the capacity to synthesize considerable quantities.3 However, studies have shown that this amino acid is actually “conditionally essential” and may become depleted during the course of catabolic insult such as injury or infection.2,3

In the small bowel mucosa, glutamine provides fuel for metabolism, regulates cell proliferation, and repairs and maintains gut barrier function.2 It is utilized at a high rate in rapidly dividing immune cells and promotes many functional activities of immune cells such as T-cell proliferation, B-cell differentiation, phagocytosis, antigen presentation, cytokine production, and neutrophil superoxide production.4 Glutamine is considered the most important nutrient for healing of the condition commonly known as “leaky gut syndrome” because it is the preferred fuel for enterocytes and colonocytes.2 A significant body of evidence now indicates that glutamine may preserve gut barrier function, or epithelial tight junctions, and prevent toxins and pathogens from exiting the lumen into the gut interstitial tissue.2,4 Disruption of tight junctions is an initial event associated with the pathogenesis of many gastrointestinal diseases, including IBS-D.2

Low glutamine levels may result in epithelial atrophy and a subsequent increase in the permeability of the intestinal barrier.5 Studies suggest that increased permeability of the mucosal barrier in the intestines may correlate with a variety of clinical disorders, including rheumatoid arthritis, celiac disease, dermatological conditions, IBS, and more.2,5 IBS-D is one of the most frequent functional gastrointestinal disorders seen by clinicians,5 affecting between 25 and 45 million people in the United States.6

A 2016 study ex vivo suggests that glutamine increases expression of claudin-1 in the colonic mucosa of patients with IBS-D.8 Glutamine effect, researchers speculate, seems to be dependent on basal expression of tight junction proteins.8

In a 2007 study of children in northeastern Brazil, low levels of serum glutamine concentration correlated with intestinal barrier disruption, inflammation, and diarrheal diseases.9,10 Intestinal permeability is also associated with the development of bacteremia, sepsis, and multiple organ failure; a 2005 study suggests that glutamine administration may improve the prognosis of critically ill patients, presumably by maintaining the physiologic intestinal barrier and by reducing the frequency of infections.11

Glutamine supplementation may also decrease bacterial translocation and intestinal permeability after intestinal injury; it has been shown to improve gastrointestinal function in Crohn’s disease and in patients with advanced esophageal cancer undergoing radiochemotherapy.5 A 2001 study found a significant clinical and endoscopic improvement in ulcerative colitis patients treated with a germinated barley foodstuff that contained glutamine-rich protein and hemicellulose-rich fiber.12

Clearly, a growing body of evidence supports the use of glutamine in clinical practice for the treatment of gastrointestinal dysfunction. Functional Medicine clinicians know that a properly functioning digestive system is critical to good health. Problems in the gut rarely stay in the gut and can be the root cause of chronic health problems like autoimmune diseases, chronic fatigue, diabetes, and more. Learn practical applications for understanding, assessing, and treating gut dysfunction in IFM’s GI Advanced Practice Module.

References

  1. Zhou Q, Verne ML, Fields JZ, et al. Randomized placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome [published online August 14, 2018]. Gut. doi:10.1136/gutjnl-2017-315136.
  2. Rao RK, Samak G. Role of glutamine in protection of intestinal epithelial tight junctions. J Epithel Biol Pharmacol. 2012;5(Suppl 1-M7):47-54. doi:10.2174/1875044301205010047.
  3. Labow BI, Souba WW. Glutamine. World J Surg. 2000;24(12):1503-1513.
  4. Newsholme P. Why is l-glutamine metabolism important to cells of the immune system in health, post-injury, surgery or infection? J Nutr. 2001;131(9):2515S-2522S. doi: 10.1093/jn/131.9.2515S.
  5. Zhou Q, Souba WW, Croce CM, Verne GN. MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome. Gut. 2010;59(6):775-784. doi:10.1136/gut.2009.181834.
  6. Facts about IBS. International Foundation for Functional Gastrointestinal Disorders. https://www.aboutibs.org/facts-about-ibs.html. Updated November 24, 2016. Accessed September 4, 2018.
  7. Coëffier M, Déchelotte P, Ducrotté P. Intestinal permeability in patients with diarrhea-predominant irritable bowel syndrome: is there a place for glutamine supplementation? Gastroenterology. 2015;148(5):1079-1080. doi:10.1053/j.gastro.2015.02.057.
  8. Bertrand J, Ghouzali I, Guérin C, et al. Glutamine restores tight junction protein claudin-1 expression in colonic mucosa of patients with diarrhea-predominant irritable bowel syndrome. JPEN J Parenter Enteral Nutr. 2016;40(8):1170-1176. doi:10.1177/0148607115587330.
  9. Guerrant RL, Oriá RB, Moore SR, Oriá MO, Lima AA. Malnutrition as an enteric infectious disease with long-term effects on child development. Nutr Rev. 2008;66(9):487-505. doi:10.1111/j.1753-4887.2008.00082.x.
  10. Lima NL, Soares AM, Mota RM, Monteiro HS, Guerrant RL, Lima AA. Wasting and intestinal barrier function in children taking alanyl-glutamine-supplemented enteral formula. J Pediatr Gastroenterol Nutr. 2007;44(3):365-374. doi:10.1097/MPG.0b013e31802eecdd.
  11. De-Souza DA, Greene LJ. Intestinal permeability and systemic infections in critically ill patients: effect of glutamine. Crit Care Med. 2005;33(5):1125-1135.
  12. Kanauchi O, Iwanaga T, Mitsuyama K. Germinated barley foodstuff feeding. A novel neutraceutical therapeutic strategy for ulcerative colitis. Digestion. 2001;63(Suppl 1):60-67. doi:10.1159/000051913.