What is the recommended dosage for glutathione supplementation?

Recommended Dosage for Glutathione Supplementation

For oral glutathione supplementation in healthy adults, 250-1000 mg daily is effective at increasing body stores of glutathione across multiple compartments, with the higher dose (1000 mg/day) showing more robust and consistent increases. 1, 2

Route-Specific Dosing Recommendations

Oral Administration (Standard Formulation)

• 250 mg/day: Produces modest increases in blood (17%) and erythrocyte (29%) glutathione levels after 6 months 2
• 1000 mg/day: Achieves 30-35% increases in erythrocytes, plasma, and lymphocytes, and 260% increase in buccal cells at 6 months 2
• Effects are dose- and time-dependent, with measurable increases beginning at 1 month and peaking around 2-6 months 2

Important caveat: Traditional oral glutathione has negligible systemic bioavailability due to hydrolysis by intestinal and hepatic gamma-glutamyltransferase, making single-dose administration ineffective 3. However, chronic daily supplementation does increase body stores 2.

Oral Administration (Liposomal Formulation)

• 500-1000 mg/day: Produces faster and more dramatic increases compared to standard formulations 4
• Maximum increases occur within 2 weeks: 40% in whole blood, 25% in erythrocytes, 28% in plasma, and 100% in peripheral blood mononuclear cells 4
• No significant difference observed between 500 mg and 1000 mg doses in the limited sample studied 4

Sublingual Administration

• 500 mg/day: Studied in patients with cardiovascular risk factors, showing improvements in lipid profile and arterial stiffness in those with baseline endothelial dysfunction 5
• This route bypasses first-pass hepatic metabolism, potentially improving bioavailability 5

Parenteral Administration (N-Acetylcysteine as Glutathione Precursor)

• 20-50 mg/kg/day of N-acetylcysteine: Recommended for pediatric parenteral nutrition to increase blood glutathione levels 6, 1
• NAC serves as a precursor that cells use to synthesize glutathione endogenously 1

Critical warning: Direct subcutaneous glutathione administration is not supported by any medical literature and carries significant risks including injection site reactions, tissue irritation, abscess formation, and unknown absorption kinetics 1.

Population-Specific Considerations

Elderly Type 2 Diabetic Patients

• 500 mg/day orally for 6 months: Significantly decreased HbA1c (Cohen's d = -0.41) and increased fasting insulin (Cohen's d = 0.56) in patients above 55 years 7
• Blood glutathione increased (Cohen's d = 1.01) and oxidative damage marker 8-OHdG decreased (Cohen's d = -1.07) within 3 months 7

Patients with Cardiovascular Risk Factors

• 500 mg/day sublingual: Reduced total and LDL cholesterol and improved arterial stiffness in those with baseline endothelial dysfunction (RHI ≤1.67) 5

Contraindicated Populations

• Cystic fibrosis patients: No data support glutathione therapy; supplementation is not recommended 1, 8
• Critically ill patients with multi-organ failure: High-dose glutamine (not glutathione, but often confused) associated with increased mortality 8
• Acute kidney injury or chronic kidney disease with kidney failure: High-dose parenteral glutamine should not be administered 8

Practical Dosing Algorithm

For general antioxidant support in healthy adults:

• Start with 500-1000 mg/day oral glutathione (liposomal formulation preferred for faster effect) 2, 4
• Expect measurable increases in 1-2 weeks with liposomal form, 1-3 months with standard form 2, 4

For elderly diabetic patients (>55 years):

• Use 500 mg/day oral glutathione for minimum 3-6 months 7
• Monitor HbA1c and fasting insulin as markers of efficacy 7

For cardiovascular risk reduction:

• Consider 500 mg/day sublingual formulation, particularly if baseline endothelial dysfunction present 5

For parenteral nutrition (when oral route unavailable):

• Use N-acetylcysteine 20-50 mg/kg/day as glutathione precursor rather than direct glutathione administration 6, 1

Common Pitfalls to Avoid

• Do not confuse glutathione with glutamine: These are different compounds with different indications and dosing 1
• Do not use single-dose oral glutathione expecting immediate effect: Chronic daily administration is required for efficacy 3, 2
• Do not attempt subcutaneous administration: No pharmacokinetic data exists and significant safety risks are present 1
• Do not use in cancer patients receiving taxane chemotherapy: Glutathione showed no benefit for preventing taxane-induced peripheral neuropathy in a large trial of 185 patients 1