Glutathione

Summary

Glutathione is a naturally occurring tripeptide composed of glutamate, cysteine, and glycine. It is the most abundant intracellular antioxidant in mammals. Clinically, intravenous glutathione is used in some jurisdictions as an adjunct in cancer chemotherapy (to reduce cisplatin-induced neuropathy), in acetaminophen overdose management, and in Parkinson's disease (investigational). It is also widely marketed as an oral supplement (with limited bioavailability) and used off-label for skin lightening via IV infusion. Nebulized and intranasal forms are under investigation for pulmonary and neurological conditions.

Mechanism of Action

Glutathione (GSH) is an endogenous tripeptide (γ-L-glutamyl-L-cysteinyl-glycine) that acts as a major intracellular antioxidant. It scavenges reactive oxygen species (ROS) and free radicals, serves as a cofactor for glutathione peroxidase and glutathione S-transferase enzymes, participates in xenobiotic detoxification via conjugation, maintains redox homeostasis by cycling between reduced (GSH) and oxidized (GSSG) forms, and supports immune function and cellular signaling.

Routes of Administration

Goals & Uses

• Parkinson's disease symptom managementNeurology (investigational)Low
• Immune function enhancementImmunologyLow
• Cisplatin-induced peripheral neuropathy preventionOncology / NeuroprotectionModerate
• Skin lightening / hyperpigmentation reductionDermatology (off Label)Low
• Acetaminophen (paracetamol) overdose adjunctToxicologyModerate
• Antioxidant support / oxidative stress reductionGeneral Health / Cellular ProtectionModerate

Contraindications

• Known hypersensitivity to glutathione or formulation excipientsAllergyHigh
• Concurrent chemotherapy regimens where GSH may reduce efficacyOncologyModerate
• Pregnancy (high-dose IV)Reproductive SafetyModerate

Adverse Effects

• Hypersensitivity / allergic reactionsImmunologicRare
• Injection site reactionsLocalCommon
• Gastrointestinal discomfortGastrointestinalUncommon
• Thyroid dysfunctionEndocrineRare
• Stevens-Johnson syndrome / toxic epidermal necrolysisDermatological (severe)Rare
• Renal dysfunction (with high-dose IV)RenalRare

Drug Interactions

• Nitroglycerin / Organic nitratesLow
• CisplatinLow
• N-Acetylcysteine (NAC)Low
• Alkylating chemotherapy agents (e.g., cyclophosphamide, melphalan)Moderate

Population Constraints

• Patients with cystinuria or cystine kidney stonesMetabolic / RenalRelative
• Pediatric patientsAgeRelative
• Patients undergoing cancer chemotherapyOncologyRelative
• Patients with asthma (nebulized route)PulmonaryRelative

Regulatory Status

• European UnionApprovedApproved: Adjunct prevention of cisplatin-induced peripheral neuropathy (Italy and select countries), Hepatoprotection in certain liver conditionsApproved as a licensed medicine in Italy (e.g., Tathion). Regulatory status varies by member state; some use it as a registered drug, others as a supplement.
• United StatesUnapprovedNot FDA-approved as a drug. Available as a dietary supplement (oral) and as compounded IV preparations. FDA has warned against IV use for skin lightening. Investigational for Parkinson's disease and other conditions.
• United KingdomUnknownNot formally approved by MHRA as a drug product. Available as a food supplement. IV preparations used in some clinical settings but not licensed. Warnings issued against unlicensed IV injections for cosmetic purposes.

IV glutathione is approved or used as a licensed medicine in Italy and some other European countries for peripheral neuropathy from cisplatin chemotherapy. In the US, it is available as a compounded preparation but is not FDA-approved as a drug. Oral glutathione supplements are sold as dietary supplements in the US. The FDA has issued warnings against IV glutathione injections marketed for skin lightening. Nebulized glutathione lacks formal regulatory approval.

Evidence & Sources

No sources recorded yet.