NAC (N-Acetyl Cysteine)
Glutathione precursor with evidence across PCOS, liver disease, OCD, and respiratory conditions.
Evidence highlight
NAC (1200mg/day) was non-inferior to clomiphene citrate for ovulation induction in PCOS in a 2003 RCT. A 2021 Cochrane-level meta-analysis confirmed benefit for live birth rates in infertile women with PCOS.
Therapeutic dosing
NAC oral
600-1800mg/day in divided doses
Lower doses (600mg BID) for general antioxidant/PCOS; higher doses for psychiatric/liver indications
PCOS protocol
600mg BID or 1200mg/day
Often combined with myo-inositol; evidence for ovulation induction comparable to clomiphene in some trials
OCD/compulsive behaviors
1200-2400mg/day
Higher end of range; takes 8-12 weeks for psychiatric effect
Drug interactions
Nitroglycerin / isosorbide — combination can cause severe hypotension and headache; avoid
Activated charcoal — reduces NAC absorption in overdose settings; IV form preferred in acute acetaminophen toxicity
Carbamazepine — NAC may increase carbamazepine levels
Anticoagulants — theoretical antiplatelet effect at high doses; monitor
Contraindications
Nitroglycerin use (hypotension risk)
Active peptic ulcer (may worsen)
Known cystinuria
Labs to monitor
Mechanism of action
NAC is the rate-limiting precursor to glutathione synthesis. It directly replenishes intracellular cysteine, which becomes depleted under oxidative stress. NAC also modulates glutamatergic neurotransmission (via cystine-glutamate antiporter), which explains its psychiatric applications in OCD, addiction, and bipolar disorder — effects unrelated to its antioxidant mechanism.
Clinical note
Two completely different mechanisms, two completely different clinical applications. Do not conflate the antioxidant/liver/PCOS use (600-1200mg) with the glutamatergic psychiatric use (1200-2400mg). The psychiatric application requires higher doses, longer treatment timelines (8-12 weeks), and different monitoring. NAC is one of the most versatile supplements in integrative practice but gets under-dosed for psychiatric indications.
Conditions commonly using NAC (N-Acetyl Cysteine)
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