Is glutamine supplementation safe and beneficial for a generally healthy adult or for patients with certain medical conditions, such as kidney or liver disease, Crohn's disease, ulcerative colitis, cancer, or HIV/AIDS?

Is Glutamine Supplementation Safe and Beneficial?

Glutamine supplementation is not recommended for generally healthy adults or for most patients with medical conditions including inflammatory bowel disease, cancer patients undergoing chemotherapy/radiotherapy, or critically ill patients, with the narrow exception of patients requiring exclusive parenteral nutrition who cannot be fed enterally. 1, 2, 3

Safety Profile and Contraindications

High-dose glutamine is contraindicated in critically ill patients with organ dysfunction, as it has been associated with increased mortality. 2, 4 Specifically:

• Do not use in patients with acute kidney injury or chronic kidney disease with kidney failure 4, 5
• Do not use in critically ill patients with multi-organ failure, where increased mortality has been documented 5, 6
• Large multicenter trials (REDOXS and MetaPlus) demonstrated trends toward increased 28-day mortality and significantly increased 6-month mortality in ventilated ICU patients receiving glutamine 6

Evidence for Specific Conditions

Cancer Patients

There is insufficient evidence to recommend glutamine supplementation during conventional chemotherapy, radiotherapy, or targeted therapy. 1, 2, 5 The evidence is heterogeneous:

• Some small studies showed benefits for mucositis, while larger placebo-controlled trials showed no effect 1
• Concerns exist about glutamine potentially fueling cancer cell metabolism 2
• One trial in autologous transplant patients reported more severe oral mucositis and increased relapses in the glutamine group 1
• Exception: Patients undergoing hematopoietic stem cell transplantation (HSCT) may receive parenteral glutamine at 0.6 g/kg/day, though evidence remains mixed 5

Inflammatory Bowel Disease (Crohn's Disease and Ulcerative Colitis)

Glutamine supplementation has no effect on disease course in IBD patients. 3 A systematic review of seven studies found:

• No effect on disease activity, intestinal permeability, or inflammatory markers 2, 3
• No changes in anthropometric or biochemical parameters regardless of route (oral, enteral, or parenteral) 3

Surgical Patients

Parenteral glutamine may be considered only in surgical patients requiring exclusive parenteral nutrition who cannot be fed enterally, at a dose of 0.35-0.5 g/kg/day. 1, 4 However:

• The recommendation is weak due to conflicting evidence 1, 5
• Most surgical patients do not require exclusive parenteral nutrition for 5-7 days, particularly after elective colorectal surgery 1
• Meta-analyses showed some benefits for infections and length of stay, but studies were underpowered with methodological concerns 1

Generally Healthy Adults

There is no evidence supporting glutamine supplementation in healthy individuals. 2 The clinical significance of increased intestinal secretory IgA as a standalone outcome is uncertain and does not translate into meaningful clinical benefits that would justify routine supplementation 2

Clinical Decision Algorithm

1. Assess nutritional route capability: Can the patient tolerate enteral nutrition? 4

   • If yes → Do not use glutamine (standard nutrition is sufficient)
   • If no → Proceed to step 2

2. Evaluate for contraindications: 4, 5

   • Acute kidney injury or chronic kidney disease? → Contraindicated
   • Multi-organ failure or critical illness with organ dysfunction? → Contraindicated
   • If no contraindications → Proceed to step 3

3. Determine specific indication: 1, 4, 5

   • Exclusive parenteral nutrition required AND cannot be fed enterally? → May consider 0.5 g/kg/day parenteral glutamine
   • HSCT patient? → May consider 0.6 g/kg/day parenteral glutamine
   • All other situations → Do not use

Important Caveats

• Oral glutamine supplementation has insufficient evidence for any clinical indication 1
• The combination of parenteral glutamine with oral/enteral nutrition lacks supporting data 1
• Most commercially available parenteral nutrition formulations do not contain glutamine, requiring separate supplementation if indicated 7
• Despite biological plausibility and some positive metabolic effects, glutamine has not demonstrated consistent improvements in morbidity, mortality, or quality of life outcomes that would justify widespread use 2