What dose of N-acetylcysteine (NAC) and glycine is required to achieve 500 mg of glutathione?

NAC and Glycine Requirements for Glutathione Production

To produce 500 mg of glutathione, you would need approximately 400-450 mg of N-acetylcysteine (NAC) and 300-350 mg of glycine in a 1:1 ratio.

Understanding Glutathione Synthesis

Glutathione is a tripeptide composed of three amino acids:

• Glutamic acid
• Cysteine
• Glycine

The primary limiting factor in glutathione synthesis is the availability of cysteine, which is typically provided through NAC supplementation due to its better stability and availability compared to direct cysteine supplementation.

Bioavailability Considerations

• L-cysteine has better bioavailability (approximately 100%) compared to NAC, which has only about 50% bioavailability 1
• NAC must be deacetylated intracellularly to provide cysteine for glutathione synthesis 2
• When taking NAC, plasma concentrations of 100 μM (therapeutically attainable) can react with plasma cystine to produce approximately 50 μM cysteine, which is sufficient to produce maximal rates of glutathione synthesis 2

Dosing Rationale

The recommended ratio for supplementation is based on several factors:

1. The molecular structure of glutathione requires cysteine and glycine in approximately equal amounts
2. Research shows that supplementation with glycine and NAC (GlyNAC) in a 1:1 ratio is effective for potentially increasing glutathione levels 3
3. Clinical trials have used various doses of GlyNAC supplementation:
   • Low dose: 2.4 g/day (1.2 g NAC + 1.2 g glycine)
   • Medium dose: 4.8 g/day (2.4 g NAC + 2.4 g glycine)
   • High dose: 7.2 g/day (3.6 g NAC + 3.6 g glycine) 3

Practical Recommendation

For 500 mg of glutathione production:

• NAC: 400-450 mg
• Glycine: 300-350 mg

This recommendation accounts for:

1. The molecular weight ratio of the amino acids in glutathione
2. The bioavailability of NAC (approximately 50%) 1
3. The need for sufficient precursors to support the complete synthesis pathway

Important Considerations

• Higher doses of NAC (1,500 mg/kg) may have pro-oxidant effects in healthy individuals, so excessive supplementation should be avoided 4
• The N-acetyl-L-cysteine isomer is more effective than the D isomer for increasing glutathione synthesis 5
• Individuals with high oxidative stress and low baseline glutathione status may benefit more from supplementation 3
• The effectiveness of supplementation may vary based on individual metabolic factors and existing glutathione levels

For optimal results, these supplements should be taken together, as they work synergistically to support glutathione production.