What amino acid can enhance immune function in critical illness?

Glutamine is the Amino Acid That Enhances Immune Function in Critical Illness

In critical illness, glutamine supplementation is the most effective amino acid for enhancing immune function, with recommended doses of 0.2-0.4 g/kg/day when parenteral nutrition is indicated. 1

Mechanism of Action and Physiological Role

Glutamine becomes conditionally essential during critical illness despite being the most abundant free amino acid in the body under normal conditions. During critical illness:

• Plasma glutamine levels fall due to increased demand for utilization in immune activity and tissue repair 1
• Low plasma glutamine levels are associated with worse outcomes 1
• Glutamine serves multiple crucial functions:
  • Primary fuel for enterocytes and immune cells 2
  • Improves gut mucosal integrity and reduces bacterial translocation 1
  • Enhances immune cell function 1
  • Decreases pro-inflammatory cytokine production 1
  • Increases glutathione levels and antioxidative capacity 1
  • Regulates ammonia and acid-base balance 1

Evidence for Glutamine vs. Other Amino Acids

Glutamine

• ESPEN guidelines strongly recommend glutamine supplementation (Grade A) at 0.2-0.4 g/kg/day when parenteral nutrition is indicated 1
• Accumulated data from clinical studies shows reduced mortality risk (RR 0.67, CI 0.48-0.92) 1
• Small studies in septic patients showed significant reduction in infectious complications and faster recovery of organ dysfunction 1
• High-dose parenteral glutamine (>0.20-0.30 g/kg/day) shows the greatest potential benefit 3

Arginine

• Arginine availability is reduced in sepsis 1
• However, supplementation may lead to unwanted vasodilation and hypotension 1
• Clinical trials show variable effects on mortality 1
• Some studies suggest possible harm in septic patients 1

Alanine and Glycine

• Neither alanine nor glycine has strong evidence supporting immune enhancement in critical illness
• Alanine and glycine are primarily used in glutamine dipeptides (alanyl-glutamine or glycyl-glutamine) to improve stability and solubility of glutamine in parenteral solutions 1
• These dipeptides serve primarily as delivery vehicles for glutamine rather than having significant independent immune-enhancing effects

Clinical Application and Safety

• Glutamine supplementation is safe with no harmful effects reported in critically ill patients at doses of 10-30g/24h 1
• Parenteral administration shows more consistent benefits than enteral administration 1, 3
• Cost-benefit analysis shows reduced hospital costs for glutamine recipients compared to controls 4
• No evidence of harm has been observed in studies conducted to date 3

Practical Recommendations

For critically ill patients requiring parenteral nutrition:

• Use glutamine-containing dipeptides (alanyl-glutamine or glycyl-glutamine)
• Administer at 0.2-0.4 g/kg/day (equivalent to 0.3-0.6 g/kg/day of alanyl-glutamine dipeptide) 1, 2
• Continue throughout the course of parenteral nutrition
• Monitor for clinical improvement in infection rates and organ function

While all four amino acids listed (glutamine, arginine, alanine, glycine) have roles in metabolism, the evidence clearly supports glutamine as having the strongest immune-enhancing effects in critical illness with established clinical guidelines recommending its use.