Glutamine is an amino acid which is used by the small bowel for energy, growth, and healing, but what about its use as a supplement for gut healing? As Rodney Dangerfield would say, “No respect”!
The use of glutamine supplementation for gut repair by holistic and functional medicine doctors has been labeled as quackery. However, there is emerging evidence that intestinal hyperpermeability (aka leaky gut) plays a central role in the pathogenesis (development) of many gut and systemic diseases. The leaky gut premise now has validity via multiple peer-reviewed scientific studies.
There is data in animals that shows glutamine facilitates gut repair. However, its clinical utility in humans is not well defined. There are recent studies that provide evidence to suggest that glutamine may play a role in gut healing in humans having therapeutic implications.
The first study provides evidence that glutamine is a logical adjunct for diarrhea-predominant IBS (IBS-D) by ameliorating transport protein malfunction (i.e. healing the leaky gut). The second and third studies relate to weight loss showing that glutamine improved glucose handling, insulin resistance, and, in the second, it favorably shifted the gut microbiome in obesity to a lean metabolism as I discuss in detail in my upcoming book The Gut Balance Revolution.
The first study mentioned above on IBS-D was led by Dr. Zhou and colleagues who reported their findings in the January issue of Gastroenterology, the top GI journal in the world. They stated, “some patients with irritable bowel syndrome with diarrhea (IBS-D) have intestinal hyperpermeability, which contributes to their diarrhea and abdominal pain. MicroRNA 29 (MIR29) regulates intestinal permeability by interfering with glutamine synthase and tight junction function.” MIR29 was found to be overexpressed in patients with IBS-D. Their research on human tissues and genetically engineered mice found that controlling the expression of this protein which regulates glutamine could be a potential target of therapy for IBS-D via improving leaky gut (gut permeability).
Based upon this research report by Zhou et al, an interesting editorial piece in the March 2015 issue of Gastroenterology raised the issue of whether glutamine supplementation could benefit those with IBS-D.
“Several studies report that glutamine content regulates intestinal permeability, partly by altering tight junction proteins. Indeed, glutamine deprivation in intestinal epithelial cells was associated with a loss of occludin, claudin-1 and ZO-1 expression leading to impaired paracellular permeability. In contrast, glutamine supplementation restores tight junction proteins and gut barrier in numerous experimental models in vivo”.
“All these data suggest that glutamine supplementation may be beneficial in IBS-D patients to reduce intestinal hyperpermeability, then possibly visceral hypersensitivity. However, the better delivery method to provide glutamine remains to be determined, as oral glutamine is rapidly absorbed by the small intestine and does not reach the colon.”
Glutamine supplementation improves insulin sensitivity in critically ill patients and prevents obesity in animals fed a high-fat diet. Four obese females were randomly assigned to 4-week supplementation with glutamine or isonitrogenous protein supplement (0.5 g/KgBW/day). In a cross-over study, insulinemia and insulin resistance declined by 20% after glutamine, but not significantly so. This pilot study showed that glutamine is safe and effective in favoring weight loss and possibly enhancing glucose metabolism. But why? How would glutamine improve glucose handling and weight loss? Read on.
The final study of interest was a randomized controlled trial involving 33 study subjects who were evaluated for the potential of glutamine supplementation on weight regulation. The study published ahead of print in January 2015 which reported that supplementation with 30 grams of glutamine in obese and overweight individuals alters gut microbiota away from obesogenic strains similar to changes seen with weight loss.
Glutamine may have numerous ways by which it supports improvements in post-prandial insulin and glucose handling. By healing the gut there would be less translocation of bacterial toxins systemically that provoke inflammation and its unhealthy consequences such as insulin resistance and fatty liver disease. Glutamine also appears to shift the gut microbiome away from an obesogenic pattern to profiles seen in those who have undergone gastric bypass surgery or have lost weight.
Stay tuned for more studies that evaluate the potential role of glutamine in the treatment of gut disease and its related systemic conditions.
To your good health.
Dr. Gerry Mullin
The Food MD