What is the recommended dosing for subcutaneous glutathione administration?

Subcutaneous Glutathione Dosing: Evidence-Based Recommendations

Direct Answer

There are no established clinical guidelines or FDA-approved protocols for subcutaneous glutathione administration, and this route lacks supporting evidence for safety or efficacy.

Evidence Review and Clinical Context

Established Routes of Administration

The available evidence demonstrates glutathione has been studied through three primary routes, none of which include subcutaneous administration:

Intravenous Administration (most studied for chemotherapy-induced neuropathy prevention):

• 1,500 mg/m² in 100 mL saline infused over 15 minutes immediately before chemotherapy (cisplatin or oxaliplatin), with some protocols adding 600 mg intramuscularly on days 2-5 1
• Alternative dosing: 2.5 g over 15 minutes before cisplatin 1
• Higher doses up to 5 g have been used immediately before cisplatin 1

Oral Administration (studied for NAFLD and skin conditions):

• 250-500 mg daily for skin lightening effects 2, 3
• 300 mg daily for nonalcoholic fatty liver disease 4
• Doses up to 1,200-1,800 mg daily have been studied for other conditions with acceptable safety profiles 5

Topical Administration:

• 0.5-2.0% glutathione formulations for skin conditions 2

Critical Safety Considerations for Subcutaneous Route

Volume and Tissue Tolerance:

• Current evidence suggests subcutaneous injection volumes above 1.5 mL are associated with injection pain and adverse events, though volumes up to 3.5 mL have been explored for biopharmaceuticals 6
• Glutathione IV formulations typically use 100 mL volumes, which would be completely inappropriate for subcutaneous administration 1

Lack of Pharmacokinetic Data:

• No published studies establish bioavailability, absorption kinetics, or tissue tolerance for subcutaneous glutathione 1
• Oral glutathione already has limited absorption and questionable bioavailability 3

Potential Complications:

• Risk of injection site reactions, tissue irritation, and unpredictable absorption
• No data on local tolerability or injection-related adverse events for this route 6

Clinical Recommendation

If glutathione therapy is clinically indicated, use established routes with evidence-based dosing:

1. For chemotherapy-induced neuropathy prevention: Intravenous 1,500 mg/m² over 15 minutes before platinum-based chemotherapy 1

2. For systemic antioxidant effects: Oral 250-500 mg daily, recognizing limited bioavailability 4, 2, 3

3. Avoid subcutaneous administration due to absence of safety data, efficacy data, and appropriate formulations for this route 1, 6

Important Caveats

• The evidence for glutathione efficacy is mixed even for established routes; some studies show benefit for neuropathy prevention 1, while others show no advantage or even harm in certain contexts 1
• Intravenous glutathione for skin lightening is contraindicated due to lack of efficacy and side effects 2
• Any off-label use should be carefully considered against established therapeutic alternatives with stronger evidence bases 7