In which medical conditions can glutathione be used?

Glutathione Clinical Applications

Glutathione has extremely limited evidence-based clinical indications, with the strongest support for preventing cisplatin and oxaliplatin-induced peripheral neuropathy in cancer patients, though even this remains controversial and is not universally recommended by major oncology societies. 1

Established Clinical Uses

Prevention of Chemotherapy-Induced Peripheral Neuropathy (CIPN)

For platinum-based chemotherapy (cisplatin/oxaliplatin specifically):

• Glutathione 1,500-2,500 mg/m² IV over 15 minutes immediately before cisplatin or oxaliplatin administration showed statistically significant reductions in neurotoxicity in five small trials 1
• After 9 weeks: 0% neuropathy with GSH vs. 66% with placebo (p=0.001) 1
• After 15 weeks: 17% neuropathy with GSH vs. 88% with placebo (p=0.001) 1
• Grade 3-4 neurotoxicity after 8 cycles: 0% with GSH vs. 26% with placebo (p=0.01) 1

Critical limitation: The American Society of Clinical Oncology states there is insufficient evidence to recommend any pharmacologic agent for prevention of oxaliplatin-induced peripheral neuropathy, including glutathione 2

Explicitly NOT effective for:

• Taxane-induced neuropathy (paclitaxel/carboplatin): A large 185-patient placebo-controlled trial showed no benefit (p=0.213), with the weekly subset actually favoring placebo (p=0.002) 1, 3

Indirect Glutathione Augmentation via N-Acetylcysteine (NAC)

Pediatric parenteral nutrition:

• NAC 20-50 mg/kg/day IV to increase blood glutathione levels in children requiring parenteral nutrition 3, 4
• NAC serves as a precursor that cells use to synthesize glutathione 4

Methemoglobinemia:

• NAC may be considered when methylene blue is contraindicated, though dosing is not standardized 3

Conditions Where Glutathione is NOT Recommended

Cystic Fibrosis

• The Cystic Fibrosis Foundation, European Society for Clinical Nutrition and Metabolism, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, and European Cystic Fibrosis Society all state there are no data supporting glutathione therapy in CF patients 3, 4

Conventional Chemotherapy

• The European Society for Clinical Nutrition and Metabolism states there are insufficient consistent clinical data to recommend glutathione supplementation during conventional cytotoxic or targeted therapy 4

Routes of Administration and Safety

Available evidence-based routes:

• Intravenous administration only for chemotherapy neuropathy prevention 1
• Oral supplementation (primarily research context) 5, 6, 7

Explicitly unsafe/unstudied routes:

• No pharmacokinetic data exists for subcutaneous bioavailability of glutathione 3
• Subcutaneous administration carries risks of injection site reactions, tissue irritation, or abscess formation 3
• No sterile, pharmaceutical-grade formulations designed for subcutaneous use exist 3

Important Distinction: Glutathione vs. Glutamine

Do not confuse these compounds—they have completely different indications:

• Glutamine (not glutathione) is recommended at 0.6 g/kg/day for hematopoietic stem cell transplantation patients 4
• Glutamine (not glutathione) at 0.35-0.5 g/kg/day may be considered for surgical patients requiring exclusive parenteral nutrition 4
• High-dose glutamine is contraindicated in critically ill patients with multi-organ failure (associated with increased mortality) 4

Research Context (Not Clinical Practice)

Conditions with preliminary evidence only (not guideline-supported):

• Neurodegenerative diseases (Alzheimer's, Parkinson's, ALS): Low glutathione levels associated with disease, but no established treatment protocols 6, 8
• Metabolic syndrome and cardiovascular disease: Higher GGT levels (marker of low GSH) correlate with disease risk, but no treatment guidelines exist 7
• Oxidative stress measurement in respiratory diseases: Decreased glutathione levels detected in asthma and COPD exacerbations, but used only as a biomarker, not a treatment 1

Clinical Algorithm for Glutathione Use

1. Is the patient receiving cisplatin or oxaliplatin chemotherapy?

   • Yes → May consider GSH 1,500-2,500 mg/m² IV before each dose, though ASCO does not formally recommend this 1, 2
   • No → Proceed to step 2

2. Is the patient a child requiring parenteral nutrition?

   • Yes → Use NAC 20-50 mg/kg/day (not glutathione directly) 3, 4
   • No → Proceed to step 3

3. Does the patient have cystic fibrosis, require conventional chemotherapy, or have taxane-induced neuropathy?

   • Yes → Do NOT use glutathione (no evidence of benefit) 3, 4
   • No → Glutathione has no established clinical indication

Critical Pitfalls to Avoid

• Never use glutathione for taxane-based chemotherapy neuropathy prevention—it is ineffective 1, 3
• Never confuse glutathione with glutamine—completely different molecules with different uses 3
• Never administer glutathione subcutaneously—no safety or efficacy data exists 3
• Do not use glutathione in cystic fibrosis patients—multiple societies recommend against it 3, 4