What is the recommended daily dose of L-glutamine (L-glutamine) for preventing mouth sores during chemotherapy?

L-Glutamine for Prevention of Chemotherapy-Induced Oral Mucositis

There is insufficient consistent clinical evidence to recommend a specific daily dose of L-glutamine for preventing chemotherapy-induced oral mucositis, as current guidelines do not support its routine use. 1

Current Guideline Recommendations

• Guidelines from the European Society for Clinical Nutrition and Metabolism (ESPEN) explicitly state there are insufficient consistent clinical data to recommend glutamine supplementation during conventional cytotoxic or targeted therapy 1
• The Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) specifically recommends against intravenous glutamine for preventing oral mucositis in patients receiving high-dose chemotherapy 1
• Evidence to support the effect of glutamine on chemotherapy-associated side effects is contradictory, with several small studies reporting positive effects while larger studies were negative 1

Evidence Analysis

• A systematic review analyzing 15 prospective and retrospective trials found positive effects of oral glutamine on mucositis in 11 of these 15 trials, but among 6 prospective placebo-controlled trials, only 2 showed benefit while 4 showed no effect 1
• Some research studies have reported positive outcomes with specific dosing regimens:
  • 2 g/m² twice daily showed reduction in duration and severity of stomatitis in a small randomized trial 2
  • 10 g three times daily throughout chemoradiotherapy course showed decreased severity of mucositis in head and neck cancer patients 3
  • 4 g twice daily as a "swish and swallow" suspension for 28 days or 4 days past resolution of mucositis showed benefit in a small pilot study 4
• A 2021 meta-analysis suggested that oral glutamine administration at medium or low daily doses may decrease the risk of severe oral mucositis, but these findings require further confirmation 5

Clinical Considerations

• Glutamine is metabolized at a high rate by cancer cells, and it has been speculated that glutamine may stabilize cancer cells against intracellular acidification 1
• There is a lack of information on glutamine's effects on tumor response, raising concerns about potential promotion of tumor growth 1
• After analyzing available trials, the MASCC/ISOO guideline group concluded there was insufficient evidence to recommend glutamine for therapeutic use 1

Recommended Alternative Approaches

• Current guidelines recommend oral care protocols for preventing oral mucositis across all cancer treatment modalities 1
• For specific chemotherapy regimens, other interventions have stronger evidence:
  • Oral cryotherapy for patients receiving bolus 5-fluorouracil chemotherapy 1
  • Low-level laser therapy for patients receiving high-dose chemotherapy with or without total body irradiation for stem cell transplantation 1
• Pain management options with better evidence include:
  • 0.5% doxepin mouthwash for pain due to oral mucositis 1
  • Transdermal fentanyl for pain due to oral mucositis in patients receiving conventional or high-dose chemotherapy 1

Conclusion

Despite some promising research studies, current clinical guidelines do not support a specific recommended daily dose of L-glutamine for preventing chemotherapy-induced oral mucositis due to inconsistent evidence and potential concerns about effects on tumor cells. Patients should instead be offered interventions with stronger supporting evidence as recommended by current guidelines.