What is the current evidence on using glutathione (GSH) in cancer treatment?

Glutathione in Cancer Treatment: Current Evidence and Recommendations

There is insufficient consistent clinical evidence to recommend glutathione supplementation in cancer treatment, and it may potentially increase cancer relapse rates in certain contexts. 1, 2

Current Evidence on Glutathione in Cancer

Dual Role in Cancer Biology

• Glutathione (GSH) serves as the most abundant antioxidant in cells with multiple functions:

  • Antioxidation and maintenance of cellular redox state
  • Detoxification of xenobiotics and carcinogens
  • Modulation of immune responses 3

• However, GSH plays contradictory roles in cancer:

  • Protective role: Detoxifies carcinogens and reduces oxidative stress
  • Pathogenic role: Elevated GSH levels in tumor cells can protect cancer cells and confer resistance to chemotherapeutic drugs 3, 4

Glutathione in Chemotherapy and HSCT

Chemotherapy Side Effects

• Some studies suggest glutamine supplementation may help with:

  • Chemotherapy-induced mucosal inflammation
  • Vomiting and diarrhea
  • Cytopenia 1

• A systematic review analyzing 15 trials found:

  • 11 of 15 trials showed positive effects of oral glutamine on mucositis
  • However, among 6 prospective placebo-controlled trials, only 2 showed benefit while 4 showed no effect 1

• For chemotherapy-induced diarrhea:

  • A meta-analysis of 8 RCTs showed significant shortening of diarrhea duration from 3 to 2 days
  • No effect on diarrhea severity was observed 1

Hematopoietic Stem Cell Transplantation (HSCT)

• Early research showed promising results:

  • One RCT found patients receiving PN supplemented with glutamine had improved nitrogen balance, fewer infections, and shorter hospital stays 1

• However, concerning evidence emerged:

  • One RCT comparing glutamine-supplemented PN with glutamine-free PN in autologous transplant patients reported more severe oral mucositis and more relapses in the glutamine group 1

• A 2009 systematic review and meta-analysis of 17 RCTs found:

  • Glutamine supplementation may decrease mucositis severity/duration
  • May reduce clinical infections (relative risk 0.75)
  • May reduce graft versus host disease (relative risk 0.42)
  • But may increase malignancy relapse rate (relative risk 2.91) 1
  • No effect on mortality was detected
  • Many studies were small with poor methodological quality 1

• A more recent RCT in 120 children with hematological malignancies found glutamine supplementation of PN:

  • Did not affect severity or duration of mucositis
  • Did not affect engraftment, graft versus host disease, relapse rate, or mortality 1

Clinical Recommendations

Current Guideline Positions

• ESPEN guidelines (2017,2021) explicitly state:

  • "There are insufficient consistent clinical data to recommend glutamine supplementation during conventional cytotoxic or targeted therapy" 1
  • "There are insufficient consistent clinical data to recommend glutamine to improve clinical outcome in patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation" 1

• The most recent clinical nutrition guidelines (2025) maintain:

  • Insufficient evidence to recommend glutathione during chemotherapy or stem cell transplantation 2
  • No clear recommendations for glutathione formulations 2

Concerns About Glutathione Use in Cancer

• Cancer protection: GSH may protect cancer cells from oxidative stress and chemotherapy 5, 6
• Drug resistance: Elevated GSH levels correlate with resistance to multiple chemotherapeutic drugs 6, 7
• Cancer progression: Excess GSH has been associated with increased metastasis 4
• Relapse risk: Evidence suggests possible increased relapse rates with glutamine supplementation in HSCT 1

Alternative Approaches

• Focus on adequate protein nutrition to maintain glutathione homeostasis 2
• Consider dietary approaches with foods rich in GSH precursors (sulfur-containing amino acids) 2
• Established interventions with proven safety profiles are preferred:
  • Dietary modifications
  • Oral supplementation of specific nutrients when deficiencies are identified
  • Lifestyle modifications 2

Clinical Considerations and Caveats

• Timing matters: Self-prescribed glutathione implementation by cancer patients lacks substantial scientific evidence for reducing toxicity (except possibly for cisplatin-related neurotoxicity) 5

• Safety concerns:

  • Long-term safety data for glutathione supplementation is lacking
  • Intravenous glutathione administration has inadequate safety data, particularly for chronic use 2
  • The potential for GSH to protect cancer cells must be weighed against any potential benefits

• Research gaps:

  • More studies are needed to better explain the relationship between GSH and cancer 5
  • Future research should address mechanistic questions regarding the distinct roles of glutathione in different stages of cancer development 6

• Experimental therapies like IV glutathione should be reserved for clinical trials or when conventional approaches have failed 2