Effects of IV Glutathione Overdose
There is no established literature documenting specific toxic effects or management protocols for IV glutathione overdose, as glutathione has demonstrated minimal adverse effects even at therapeutic doses and no documented toxicity threshold has been identified in clinical studies. 1
Available Safety Data
The current evidence base reveals significant gaps in understanding glutathione toxicity:
- No long-term safety studies exist for IV glutathione administration at any dose or for any indication, despite widespread clinical use 1
- Clinical trials using IV glutathione for chemotherapy-induced neuropathy prevention (doses of 1,500-3,000 mg/m²) reported either no adverse effects or minimal side effects, but treatment durations were limited to weeks rather than chronic administration 2, 1
- Systematic reviews of IV glutathione for preventing chemotherapy toxicity and as adjuvant therapy for Parkinson's disease (10 trials total) found minimal to no adverse effects, though all had short treatment durations 1
Theoretical Concerns in Overdose Scenarios
Based on glutathione's metabolic role, potential overdose effects might include:
- Altered melanin production: Glutathione shifts melanin synthesis from brown (eumelanin) to red (pheomelanin), which may theoretically increase sun-induced skin cancer risk in previously protected individuals, though this concern relates to chronic cosmetic use rather than acute overdose 1
- Metabolic disturbances: As glutathione is the most abundant non-protein thiol protecting cells from oxidative stress, supraphysiologic levels could theoretically disrupt normal redox signaling, though this has not been documented clinically 1, 3
Clinical Management Approach
Given the absence of documented toxicity:
- Supportive care is the primary management strategy, as no specific antidote or reversal agent exists for glutathione 1
- Monitor vital signs and general clinical status, as complications from IV infusions themselves (infection, thrombophlebitis, fluid overload) may be more relevant than glutathione-specific toxicity 1
- No specific laboratory monitoring has been established for glutathione overdose, as therapeutic monitoring parameters have not been defined even for intended use 1
Critical Knowledge Gap
Regulatory assessment of systemic glutathione administration appears urgently needed, as the compound is used clinically without adequate safety data for any route of chronic administration, and particularly given reports of patients purchasing glutathione online for self-administration 1