Properties and Uses of Glutamine in Clinical Practice
Glutamine is a conditionally essential amino acid that serves as a substrate for gluconeogenesis, increases intestinal cellularity, and is commonly supplied in total parenteral nutrition for critically ill patients. 1
Glutamine's Role in Total Parenteral Nutrition (TPN)
- Glutamine is the most abundant free amino acid in the body and has been increasingly incorporated into total parenteral nutrition formulations, particularly for critically ill patients 1
- When PN is indicated in ICU patients, parenteral glutamine supplementation (0.2-0.4 g/kg/day of L-glutamine or 0.3-0.6 g/kg/day of alanyl-glutamine dipeptide) is recommended 1
- Traditionally, L-glutamine was omitted from standard TPN formulations because crystalline L-glutamine is poorly soluble and degrades during heat sterilization, but glutamine-containing dipeptides (alanyl-glutamine or glycyl-glutamine) now provide stable and soluble alternatives 1
- Clinical studies have shown that glutamine-supplemented TPN reduces infectious complications, shortens hospital length of stay, and improves glucose tolerance in critically ill patients 2
Effects on Intestinal Cellularity
- Glutamine supplementation maintains intestinal structure and function, preventing intestinal atrophy associated with glutamine-free parenteral nutrition 3
- Studies demonstrate that glutamine-enriched TPN maintains both B and T cell populations in the gut at levels similar to normal feeding, while standard TPN solutions lead to depletion of these immune cells 4
- Glutamine serves as a primary energy substrate for rapidly dividing cells, particularly enterocytes, helping to maintain intestinal mucosal integrity 5
- The addition of glutamine to TPN has been shown to increase intestinal cellularity and prevent increased intestinal permeability 3
Glutamine as a Conditionally Essential Amino Acid
- Under normal conditions, glutamine is not an essential amino acid as it has an endogenous production rate (predominantly in skeletal muscle) of approximately 50-80 g/24h for an adult 1
- However, during critical illness, glutamine becomes "conditionally essential" because the increased demand for its utilization (for immune function and tissue repair) exceeds the body's capacity to produce it 1
- In critically ill patients, plasma glutamine levels often fall, and this hypoglutaminemia is associated with worse clinical outcomes 1
- The body's inability to maintain adequate glutamine levels during severe stress states is why supplementation is often recommended 5
Role in Gluconeogenesis
- Glutamine is a major substrate for gluconeogenesis, serving as a carrier for nitrogen and carbon between organs 1
- It participates in protein and glucose metabolism and is involved in the regulation of ammonia and acid-base balance 1
- During critical illness, there is increased dependence on glutamine as a gluconeogenic substrate due to increased protein catabolism and the inability of exogenous glucose to inhibit gluconeogenesis 1
- This role in gluconeogenesis becomes particularly important in conditions like severe acute pancreatitis, where substrate metabolism is similar to that in severe sepsis or trauma 1
Clinical Applications and Recommendations
Glutamine supplementation is particularly beneficial in specific clinical scenarios:
- Acute pancreatitis: When PN is indicated, parenteral glutamine supplementation (>0.30 g/kg Ala-Gln dipeptide) should be considered 1
- Critically ill ICU patients: Glutamine supplementation has been associated with reduced mortality and improved morbidity with reduced infections 1
- Surgical patients requiring exclusive PN: Parenteral glutamine supplementation may be considered, though evidence is less strong than for critical illness 1
Caution should be exercised with indiscriminate use of glutamine supplementation for all critically ill patients, as recent evidence suggests potential harm in certain subgroups 1