Side Effects of Intravenous Glutathione
Intravenous glutathione is generally well-tolerated with minimal adverse effects in most clinical contexts, though serious systemic inflammatory reactions have been reported with unregulated high-dose formulations, particularly in nutritionally compromised patients.
Common and Mild Side Effects
The most frequently reported adverse effects of IV glutathione are mild and self-limited:
- Nausea and vomiting occur occasionally but are typically manageable 1, 2
- No significant safety concerns were identified in controlled clinical trials using standard dosing protocols 1
- Minimal toxicity has been documented in human studies, with glutathione demonstrating a favorable safety profile compared to other antioxidant therapies 3
Serious Adverse Events with Unregulated Products
A critical distinction exists between pharmaceutical-grade and unregulated cosmetic glutathione products:
- Systemic inflammatory response syndrome (SIRS) has been reported following high-dose unregulated glutathione infusions, presenting with shock, hyperpyrexia (>41°C), marked leukocytosis (WCC 26 × 10⁹/L), elevated inflammatory markers (CRP 160 mg/L, procalcitonin 28.8 µg/L), acute liver injury (ALT 311 IU/L), and coagulopathy 4
- Endotoxin contamination of unregulated products administered in non-clinical settings represents a significant risk 4
- Synergistic toxicity may occur in nutritionally compromised patients, particularly those with prolonged low nutritional intake 4
Hematologic Effects When Combined with Chemotherapy
When glutathione modulation is attempted alongside chemotherapy:
- Enhanced myelosuppression occurs when combined with melphalan, showing significantly greater leukopenia and thrombocytopenia (P < .001) compared to chemotherapy alone 2
- This represents an interaction effect rather than direct glutathione toxicity 2
Special Population Considerations
Patients with kidney disease require caution, as high-dose parenteral glutamine (a glutathione precursor) is contraindicated in critically ill patients with acute kidney injury or chronic kidney disease 5, 6
Electrolyte monitoring is warranted when administering IV glutathione, particularly in patients with pre-existing renal dysfunction or when combined with other intravenous therapies like Myers' cocktail 5
Clinical Context and Dosing
The safety profile varies significantly with formulation and setting:
- Pharmaceutical-grade glutathione (1,400 mg three times weekly) demonstrated excellent tolerability with no withdrawals due to adverse events in controlled trials 1
- High-dose therapeutic glutathione (50-100 μmol/h/kg continuous infusion) showed protective effects in liver transplantation without significant toxicity 3
- Unregulated cosmetic formulations carry substantially higher risk, particularly when administered outside clinical settings 4
Critical Pitfalls to Avoid
- Never use unregulated glutathione products marketed for cosmetic purposes (e.g., skin lightening), as these lack quality control and carry risk of contamination 4
- Screen for concurrent medications that may affect nutritional status or increase vulnerability to adverse reactions, such as GLP-1 agonists (tirzepatide) that reduce oral intake 4
- Avoid administration in non-clinical settings where emergency management of severe reactions is unavailable 4
- Consider baseline nutritional status before administration, as compromised patients may be at higher risk for inflammatory responses 4