NAC (N-Acetylcysteine) — The Glutathione Precursor
NAC is a precursor to cysteine and glutathione — the body's master antioxidant. It is FDA-approved for acetaminophen overdose and has been used in medicine for decades. In aging, NAC restores declining glutathione levels and reduces oxidative stress across multiple organ systems.
Mechanism of Action
NAC is deacetylated to cysteine, the rate-limiting substrate for glutathione synthesis. Elevated glutathione reduces oxidative damage to DNA, proteins, and lipids. NAC also has direct antioxidant activity (thiol group), mucolytic properties, and modulates NF-κB and Nrf2 pathways.
Human Trial Evidence
The GlyNAC trial (Kumar et al., 2021) showed GlyNAC supplementation in older adults corrected glutathione deficiency, reduced oxidative stress markers by 50%, improved mitochondrial function, and improved physical performance over 24 weeks. Multiple trials confirm NAC reduces oxidative stress in aging, COPD, and cardiovascular disease.
Dosing Protocol
600–1,200 mg/day. GlyNAC protocol: 0.81 mg/kg NAC twice daily. Higher doses (1,800–2,400 mg/day) used in clinical settings. Take with food to reduce GI effects. Liposomal NAC has better bioavailability.
Safety & Contraindications
Well-tolerated at standard doses. GI side effects (nausea, vomiting) at doses >1,200 mg/day. Rare: anaphylactoid reactions (more common with IV administration). May reduce efficacy of nitroglycerin — avoid combination. Theoretical concern: NAC may reduce efficacy of some chemotherapy agents.