N-Acetyl Cysteine (NAC)
N-acetylcysteine is an acetylated form of cysteine, the amino acid that limits how fast cells make glutathione. It has been an FDA-approved drug since 1963, first as an inhaled mucolytic and later as the antidote for acetaminophen overdose, and that history is the source of its unusual status as a supplement. Taken by mouth, only about 6-10% reaches the circulation intact.
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What It Does
NAC is deacetylated to cysteine, which cells use to rebuild glutathione. In acetaminophen overdose, the liver produces a toxic metabolite, NAPQI, faster than glutathione can neutralize it; NAC restores glutathione and prevents liver necrosis. In a multicenter study of more than 2,500 overdoses, oral NAC started within 8-10 hours kept hepatotoxicity to about 6%, and it still helped when started later (Smilkstein 1988). Its free thiol group also breaks disulfide bonds in mucus, which is the basis of its mucolytic use.
Supplement uses have uneven support. In COPD, 600 mg a day for three years did not reduce exacerbations or slow lung function decline in the BRONCUS trial (Decramer 2005), while 600 mg twice a day for one year reduced exacerbations by about 22% in the Chinese PANTHEON trial (Zheng 2014). Dose may explain the difference. NAC also affects glutamate signaling through the cystine-glutamate exchanger, which led to psychiatric trials; in trichotillomania, 1,200-2,400 mg a day produced much or very much improvement in 56% of patients versus 16% on placebo (Grant 2009). Trials in addiction, bipolar depression, and other conditions have been mixed, and most are small.
Bioavailability limits everything else. Extensive first-pass metabolism leaves oral bioavailability at about 6-10%, with a half-life of about two hours (Borgström 1986). Glutathione supplements fare worse, since glutathione itself is broken down in the gut, which is one reason NAC is used as a precursor instead.
The regulatory dispute started in 2020, when FDA told companies selling NAC for hangovers that, because it was approved as a drug before anyone sold it as a supplement, it could not legally be a supplement at all. Amazon removed many NAC listings in 2021. After industry petitions and a lawsuit, FDA issued guidance in 2022 saying it would not take enforcement action against otherwise lawful NAC supplements (FDA 2022).
Forms and Bioavailability
The standard supplemental form.
| Form | Absorption | Typical dose | Cost |
|---|---|---|---|
| N-Acetyl CysteineNAC, acetylcysteine | LowOral bioavailability is roughly 4-10% because of extensive first-pass metabolism. Deacetylated to cysteine, the rate-limiting amino acid for glutathione synthesis. | 600-1,800 mg daily in divided doses | Low |
Typical Dosing
Supplements commonly provide 600-1,800 mg per day in divided doses.
What to Look For
NAC is sold mainly as 600 mg capsules. Trial doses for most uses run 1,200-1,800 mg a day in divided doses. A sulfur smell when the bottle is opened is normal and does not mean the product is spoiled.
The most common side effects are nausea, vomiting, and diarrhea. NAC can intensify the headache and blood pressure drop from nitroglycerin. Self-treatment of a suspected acetaminophen overdose with supplement NAC is never appropriate; it requires emergency care and timed blood levels.
Red flags: NAC sold as a hangover cure, "liver detox" blends with unstated amounts, and liposomal glutathione marketed as a superior substitute.
N-Acetyl Cysteine
Inexpensive and reasonably supported for a few specific uses. Poorly absorbed, which is why trial doses run well above a gram a day.
What to look for: 600 mg capsules from a third-party tested brand. A sulfur odor is expected.
Find on iHerb Affiliate linkProducts on Titrate
2,760 of the 214,745 labels in the NIH Dietary Supplement Label Database list N-acetyl cysteine (NAC) as an active ingredient (1,211 on market). 408 are sold as N-acetyl cysteine (NAC) products by name.
Top on-market labels, ranked by label completeness and simplicity:
N-Acetyl Cysteine (NAC) does not have its own search category yet. Each product above links to its full label in the NIH database.
Related Tools
References
US Food and Drug Administration. Policy Regarding N-acetyl-L-cysteine: Guidance for Industry.
Borgström L, Kågedal B, Paulsen O. Pharmacokinetics of N-acetylcysteine in man. Eur J Clin Pharmacol. 1986;31(2):217-222.
Smilkstein MJ, et al. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med. 1988;319(24):1557-1562.
Decramer M, et al. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial. Lancet. 2005;365(9470):1552-1560.
Grant JE, Odlaug BL, Kim SW. N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study. Arch Gen Psychiatry. 2009;66(7):756-763.
Zheng JP, et al. Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. Lancet Respir Med. 2014;2(3):187-194.
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