What are the contraindications for glutathione (GSH) supplementation?

Glutathione Contraindications

Absolute Contraindications

Glutathione has no formally established absolute contraindications in medical literature, but specific safety concerns exist based on route of administration and clinical context. 1

For Topical/External Use

• Known allergy or hypersensitivity to glutathione - discontinue immediately if allergic symptoms or skin abnormalities develop 1
• Avoid contact with eyes during topical application 1

For Intravenous Administration

• No established contraindications exist in published guidelines, though IV glutathione for cosmetic skin lightening lacks adequate safety data for chronic use 2
• Subcutaneous administration should be avoided entirely - no pharmacokinetic data exists for this route, posing significant risks including injection site reactions, tissue irritation, abscess formation, and unknown systemic effects 3

Clinical Context-Specific Considerations

Chemotherapy-Related Use

Glutathione should NOT be used for preventing taxane-induced peripheral neuropathy - a large placebo-controlled trial of 185 patients receiving paclitaxel/carboplatin demonstrated no benefit, suggesting GSH is ineffective against taxane-induced neuropathy 4

For platinum-based chemotherapy neuropathy prevention, the evidence is mixed:

• Five small trials showed statistically significant reductions in neurotoxicity with GSH (1.5-2.5g IV) before cisplatin or oxaliplatin 4
• However, these benefits were primarily demonstrated with cisplatin and oxaliplatin, not carboplatin 4

Cystic Fibrosis

There are no data supporting the use of glutathione therapy in CF patients - supplementation is not recommended per ESPEN-ESPGHAN-ECFS guidelines 4

Safety Profile for Chronic Use

The most critical limitation is the complete absence of long-term safety data for any systemic glutathione administration 2:

• No studies exist evaluating IV glutathione safety for chronic use (for any indication) 2
• Most clinical trials reporting minimal adverse effects had treatment durations of only a few doses (IV) or 4-12 weeks maximum 2
• Potential concern for increased skin cancer risk - the switch from brown to red melanin production may increase sun-induced skin cancer risk in previously protected individuals using glutathione for skin lightening 2

Practical Recommendations

If glutathione supplementation is clinically indicated, use N-acetylcysteine (NAC) as a safer alternative - NAC 20-50 mg/kg/day increases blood glutathione levels and has established safety profiles 3, 5:

• NAC is well-tolerated when used for COPD (600mg twice daily) with minimal adverse effects 5
• When added to parenteral nutrition, NAC decreases liver enzyme elevations with minimal side effects 5
• In the largest COPD study (1,006 patients), adverse effects did not differ significantly between NAC and placebo 5

Key Safety Precautions

• Perform skin testing before topical use on a small area of the arm 1
• Keep out of reach of children 1
• Avoid unregulated online sources - reports exist of glutathione purchased online without pharmaceutical-grade quality control 2
• No sterile, pharmaceutical-grade formulations exist for subcutaneous use 3