🔑 Core Function

• ⚡ Redox balance: The primary intracellular antioxidant; maintains the cell’s redox environment and GSH:GSSG ratio as the “redox currency” of the cell.
• 🧪 Detoxification: Conjugates toxins, drugs, and heavy metals via glutathione-S-transferases for excretion.
• 🔄 Enzyme cofactor: Required for glutathione peroxidases (selenium-dependent) and glutathione reductase (riboflavin-dependent).
• 📡 Cell signalling: Involved in apoptosis regulation, immune modulation, and gene expression pathways.

🧬 Family & Essentiality

🌿 Plain-Language Summary

Glutathione is often called the body’s “master antioxidant” 🛡️. It works inside every cell, recycling antioxidants like vitamin C and E while neutralising harmful molecules. Most dietary glutathione is broken down during digestion; instead, your body synthesises it from amino acids, especially cysteine.

⚗️ Molecular & Chemical IDs

• Forms: Reduced (GSH) ↔ Oxidised (GSSG)
• Key enzymes: Glutathione peroxidases (selenium-dependent 🪙), glutathione reductase (riboflavin-dependent 🌟), glutathione-S-transferases (detoxification)

⚡ Expanded Functions

• 🛡️ Neutralises peroxides, lipid peroxyl radicals, and reactive oxygen/nitrogen species
• ♻️ Regenerates vitamin C, vitamin E, and thioredoxin
• 🚮 Phase II detoxification: Conjugates xenobiotics, drugs, alcohol metabolites, and pollutants
• 🧬 Maintains thiol status of proteins; regulates enzyme activity and transcription factors (e.g., NF-κB)

🍽️ Support & Bioavailability

✅ Supports synthesis

• Adequate protein and sulphur amino acids (cysteine, methionine)
• N-acetylcysteine (NAC) as a clinically used precursor
• Selenium 🪙 (for GPx enzymes)
• Riboflavin 🌟 (for glutathione reductase)
• Vitamin C 🍊 and α-lipoic acid 🔗 (support recycling)

❌ May reduce status

• Protein-energy malnutrition
• Chronic oxidative stress (smoking, alcohol excess, inflammation)
• Acetaminophen (paracetamol) overdose — depletes hepatic glutathione
• Low selenium, riboflavin, or cysteine availability

🇦🇺 Australian NRVs

❌ No NRV for glutathione itself. Adequacy relies on:

• Protein (for amino acid precursors)
• Selenium (for GPx enzymes)
• Riboflavin (for glutathione reductase)

🥗 Food Sources

• Precursors: Meat, poultry, dairy, legumes, soy
• Sulphur-rich foods: Garlic, onions, cruciferous vegetables 🌱
• Fruits & veg (regeneration support): Citrus, kiwi, capsicum
• Direct glutathione sources: Avocado, spinach, asparagus — but levels decrease with cooking

🧪 Testing & Monitoring

• Research use: Plasma or erythrocyte GSH:GSSG ratio = oxidative stress marker
• PIVKA-II: Not relevant (Vitamin K marker) — but oxidative stress panels may include GSH
• Not a routine pathology test in Australia
• Low GSH levels observed in chronic disease, HIV, diabetes, neurodegenerative disorders

🔗 Interactions

• 🪙 Selenium: Cofactor for glutathione peroxidases
• 🌟 Riboflavin (B2): Supports glutathione reductase
• 🍊 Vitamin C: Recycles GSH from GSSG
• 💊 Alcohol & paracetamol: Deplete hepatic GSH stores
• 🔗 α-lipoic acid: Enhances redox cycling with GSH

📊 Evidence Snapshot

• 🔬✅ Established: Central to antioxidant defence, detoxification, redox balance
• 🧪⚖️ Promising/mixed: Research in immune modulation, neurodegenerative conditions (Parkinson’s, Alzheimer’s), and skin photoprotection
• ⚠️❌ Unproven/hype: High-dose oral supplements, skin-lightening drips, or IV therapies lack consistent evidence in healthy populations