What is the maximum daily dose of glutathione for oral and intravenous administration in adults?

Maximum Daily Dose of Glutathione

For intravenous glutathione, the maximum dose studied in clinical trials is 2.5 g (2500 mg) administered as a single infusion before chemotherapy, though most studies used 1.5 g/m² body surface area. 1 For oral glutathione, doses up to 1000 mg/day have been studied for safety and efficacy in healthy adults, with no serious adverse events reported. 2

Intravenous Administration

The evidence-based dosing range for IV glutathione is 1.5-2.5 g per administration:

• 1.5 g/m² body surface area (approximately 2.5-4 g for average adults) was used in multiple chemotherapy neuropathy prevention trials, administered over 15 minutes immediately before platinum-based chemotherapy 1
• 2.5 g total dose over 15 minutes was the highest single dose studied in the Bogliun 1996 trial for cisplatin-induced neuropathy 1
• These doses were given with each chemotherapy cycle (typically every 2-3 weeks), not daily 1

Critical safety consideration: The American Society of Clinical Oncology found that glutathione is ineffective for taxane-induced neuropathy (paclitaxel/carboplatin) in a 185-patient trial, though it showed benefit for cisplatin and oxaliplatin-induced neuropathy in smaller studies 3

Oral Administration

The maximum studied oral dose is 1000 mg/day:

• 1000 mg/day was the highest dose in a 6-month randomized controlled trial of 54 healthy adults, which increased glutathione levels by 30-35% in blood compartments with no serious adverse events 2
• 500 mg/day showed clinical skin-brightening effects in dermatological studies 4
• 250 mg/day was effective at increasing blood glutathione levels by 17-29% after 6 months 2

Important limitation: Oral glutathione has negligible systemic bioavailability due to hydrolysis by intestinal and hepatic gamma-glutamyltransferase—a single 3 g oral dose did not increase plasma glutathione levels in healthy volunteers 5. However, chronic daily supplementation (250-1000 mg/day) does increase body stores over time 2

S-Acetyl Glutathione (Modified Form)

For S-Acetyl Glutathione, the no-observed-adverse-effect level (NOAEL) is 1500 mg/kg/day in animal studies, which translates to approximately 105,000 mg/day for a 70 kg human using standard safety factors, though human studies have not tested doses this high 6. S-Acetyl Glutathione can be taken with meals for convenience 7

Alternative: N-Acetylcysteine (Glutathione Precursor)

If the goal is to increase glutathione levels systemically, N-acetylcysteine (NAC) 20-50 mg/kg/day is recommended as a more bioavailable precursor 3. For a 70 kg adult, this equals 1400-3500 mg/day of NAC, which cells convert to glutathione 3

Dosing Algorithm

For therapeutic glutathione supplementation:

1. If parenteral route is required: Use 1.5 g/m² IV over 15 minutes (maximum 2.5 g per dose), administered intermittently (not daily) 1
2. If oral supplementation is preferred: Start with 500 mg/day, may increase to 1000 mg/day for enhanced effect 2
3. If bioavailability is a concern: Consider NAC 1400-3500 mg/day instead of glutathione 3
4. If using S-Acetyl Glutathione: Doses up to 1000 mg/day appear safe based on standard glutathione studies, though specific long-term human data is limited 6

Critical Pitfalls to Avoid

• Do not confuse glutathione with glutamine—they are different compounds with different indications and dosing 3
• Do not use IV glutathione for taxane-based chemotherapy neuropathy prevention—it is ineffective 3
• Do not expect immediate systemic effects from single oral doses—chronic daily supplementation over months is required to increase body stores 5, 2
• Avoid IV glutathione in patients with contraindications to rapid infusions—anaphylaxis and hepatotoxicity have been reported with IV use 8