Glutamine: A misunderstood amino acid with therapeutic potential

Background: Glutamine is an amino acid with trophic activity in the small intestine. The small intestine derives exogenous glutamine from foods and endogenous glutamine from arterial blood. Glutamine is vital for the rapidly proliferating enterocytes lining the intestinal mucosa and promotes the expression of proteins in the tight junctions, strengthening the barrier function and reducing gut permeability. With excessive physical activity, malnutrition, acute and chronic illnesses, sarcopenia or prolonged fasting, plasma levels drop. When glutamine is depleted, the small intestine atrophies causing increased gut permeability and bacterial dislocation. The use of intravenous glutamine is well established in critical medicine, by increasing depressed glutamine plasma levels intestinal atrophy is averted. Therefore, glutamine is classified as a conditionally essential amino acid. Aim: To calculate the amounts of glutamine derived from both food and endogenous processes and to establish a suitable dosage for oral supplementation. Methods: The contribution of dietary amino acids and endogenous glutamine was assessed and compared. The pharmacokinetics of glutamine supplementation was reviewed. Results: Approximately 88% of the glutamine metabolised daily is endogenously produced. Almost half of this comes from muscle protein breakdown. Studies with supplemental free-form glutamine for treating intestinal permeability, at doses based on dietary intake, have not yielded positive results, whereas doses of 30 g glutamine, similar to daily amount metabolised by the enterocytes yielded positive results. Discussion: Clinical doses of free-form glutamine for intestinal disorders should be akin to the daily amount of glutamine metabolised by the small intestine rather than the daily dietary intake.