Does L-Glutamine worsen Inflammatory Bowel Disease?

One of my favorite things about school and interacting with others is when long-held beliefs I have become challenged. I used to get all twisted up inside and waste time arguing only to find in most cases, no progress was made on either side. And of course, only one of us was ahead, rather than both of us being ahead.


These days, my response is, “Okay! Direct me to some reading please and/or explain.” In many cases I’m pleasantly surprised. And while I’m still striving to reach 100% impartiality while reading much of what I’m exposed to, I can certainly say I’m much more grown up than I was in the past.


Today the whipping post is L-Glutamine. Something I have read much about and have used extensively in my own healing journey. I keep hearing this idea among some clinicians and in some of my classes that glutamine in acute instances of inflammatory bowel disease is contraindicated.


L-Glutamine (which I’ll refer to here on out as glutamine) is a popular dietary supplement among those suffering from or treating chronic conditions of the digestive tract.


Glutamine is a non-essential amino acid. This means our bodies can make it and we don’t need to concern ourselves with getting extra from our diet, at least most of the time.


Non essential nutrients become “conditionally essential,” under certain circumstances. This explains why certain dietary strategies may work for some and not others… a whole different topic!


Glutamine is recognized by many investigators as conditionally essential in cases of major acute stress or trauma. Examples would be surgery, burns, severe pancreatitis and sepsis. Basically issues that would hospitalize you.


But there is thought that glutamine may also be conditionally essential in less severe and more chronic conditions. In alternative health circles, treating chronic digestive issues with oral glutamine supplements is vogue. Going without glutamine in these instances might even be viewed as heresy!


The rationale behind the use of glutamine in this manner is the fact that it is an important fuel source for rapidly dividing cells. This includes enterocytes, the cells that line the small intestine and colon. This is partly because glutamine is critical in the production of pyrimidine and purine synthesis, the raw material that help us make more DNA and RNA.


Further, cell and animal models suggest glutamine might be helpful via all the mechanisms summarized in this table below.


Unfortunately, there doesn’t seem to be much in the way of clinical evidence in humans supporting this practice.


There is data supporting the idea that in acute stress, tissue use of glutamine exceeds what we can make endogenously. And provision of extra glutamine may improve clinical outcomes.


But for less severe, chronic digestive conditions, improved clinical outcome as a result of glutamine supplementation is largely speculation.


In addition, there is some clinical evidence suggesting that supplementation of glutamine in chronic inflammatory bowel disease may be harmful. Particularly in the context of active disease or acute flares.


In one study, Akobeng and friends randomized 18 children to receive either 4 weeks of a diet with low glutamine content or high glutamine content. Indices of disease activity improved in the low glutamine group, but not the glutamine group.


The same investigators in the study above randomized 16 children with active Crohn’s to either of the two diets while looking at markers for intestinal permeability as the main outcome. After 4 weeks, improvement was seen in both groups, but greater improvement in the low glutamine group.


Another study in the Journal Nature included 19 adults in the active stage of Crohn’s disease receiving TPN (IV nutrition) enriched with glutamine dipetide versus non glutamine enriched formulation as control. After 1 week, there were no changes in indices of disease activity, intestinal permeability or hospital stay duration. Also worthy of noting was that 56% percent of the treatment group versus 36% of controls experienced complication requiring surgery.


Hond and pals took 14 adults with Crohn’s disease and randomized them to 28g/day of glutamine or glycine control, orally. After 4 weeks there were no changes in disease activity scales. However, the glutamine group had worsened indices of intestinal permeability.


In support of of the use of both glutamine and whey protein in Crohn’s disease, Benjamin and colleagues randomized 15 individuals in remission to receive either 0.5g/kg (ideal weight) of glutamine or whey protein. Intestinal permeability decreased in both groups, and intestinal morphology showed improved enterocyte characteristics.


This isn’t particularly strong evidence condemning or supporting the use of glutamine in the context of inflammatory bowel disease. First, these studies have a small number of subjects. Second, the clinical usefulness of assessing intestinal permeability and laboratory parameters alone is questionable. It would be better to look at the frequency and severity of weight loss, abdominal pain, diarrhea, fever and extraintestinal signs. Not all of the investigators in these studies did that.


There is reason to believe that glutamine supplementation could worsen flares in inflammatory bowel diseases. Crohn’s is characterized by neutrophilic infiltration of epithelial cells and a dysregulated T cell response. Recall that glutamine is a major fuel source for rapidly dividing cells. Immune cells fall under this category. This could mean that glutamine has the potential to worsen any active autoimmune disease.


I mentioned that I had believed glutamine was an integral part of my own healing process. Today I would tell you that it was, but it was likely an incredibly small needle mover, if one at all. I think we forget that when we embark on our own paths to fix our health, we often change our behavior in several domains. Not only was I taking glutamine, I was going to bed on time, I was promoting mobilization and excretion of toxicants aggressively, I cleaned up my diet, I did a lot LESS exercise… the list goes on. That list includes factors that are much more likely to give you more bang for your buck than glutamine will.


It seems that glutamine should not necessarily be considered contraindicated in inflammatory bowel disease.  Instead we should exercise caution with it’s use and continue to pay close attention to changes in clinical parameters.


In the next post, we’ll look at dietary supplements and strategies that have been investigated clinically. Be well and stay tuned!


Photo Credit: Domink Wycislo


For your viewing pleasure


Akobeng, Anthony K., et al. “Double-blind randomized controlled trial of glutamine-enriched polymeric diet in the treatment of active Crohn’s disease.” Journal of pediatric gastroenterology and nutrition 30.1 (2000): 78-84


Akobeng, Anthony K., et al. “Glutamine supplementation and intestinal permeability in Crohn’s disease.” Journal of Parenteral and Enteral Nutrition 24.3 (2000): 196-196


Alkhawtani, Daniyah, et al. “Effect of Glutamine Supplementation in Patients with Inflammatory Bowel Diseases.” Nutrition and Food Sciences (2016)


Benjamin, Jaya, et al. “Glutamine and whey protein improve intestinal permeability and morphology in patients with Crohn’s disease: a randomized controlled trial.” Digestive diseases and sciences 57.4 (2012): 1000-1012


Den Hond, Elly, et al. “Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn’s disease.” Journal of Parenteral and Enteral Nutrition 23.1 (1999): 7-11


Ockenga, J., et al. “Glutamine-enriched total parenteral nutrition in patients with inflammatory bowel disease.” European journal of clinical nutrition 59.11 (2005): 1302-1309
Zeisel, Steven H. “Modern nutrition in health and disease.” Wolters Kluwer Health Adis (ESP). 2012

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