N-Acetyl L-Cysteine

NAC supplies cysteine, the rate-limiting amino acid for glutathione synthesis. Glutathione is the body's principal intracellular antioxidant, and cysteine availability constrains how much can be made.

In paracetamol overdose this is the entire mechanism: the toxic metabolite NAPQI depletes glutathione, and NAC restores the substrate for regenerating it.

Separately, NAC modulates glutamate via the cystine-glutamate antiporter, raising extracellular glutamate in a way that affects reward and compulsive behaviour circuits. This is the mechanism behind the psychiatric research and is distinct from the antioxidant role.

Paracetamol overdose: definitively effective and standard of care, one of the clearest evidence bases in this entire library.

Trichotillomania: a randomised controlled trial reported significant improvement versus placebo, with roughly half of participants responding.

Mixed to modestly positive results in obsessive-compulsive disorder, substance use disorders, and as an adjunct in schizophrenia.

Respiratory: used as a mucolytic, with evidence in COPD of variable strength.

Oral capsules or effervescent tablets. It has a notable sulphurous smell and taste, which is characteristic rather than a sign of degradation.

Gastrointestinal upset is the most common tolerability issue and is reduced by taking it with food, though absorption may be modestly better fasted.

Generally very well tolerated, with a large clinical safety database from decades of use.

Most common: nausea, vomiting, diarrhoea, and the sulphur smell.

Intravenous administration in overdose settings can produce anaphylactoid reactions; this is a feature of rapid IV infusion and not of oral supplement use.

Some evidence suggests high-dose antioxidant supplementation may blunt exercise-induced training adaptations, which is a consideration if you train for adaptation rather than performance on the day.

Widely combined with other supplements without documented interaction concerns.

The relevant interaction is theoretical and worth knowing: nitroglycerin combined with NAC can potentiate hypotension and headache.

The training-adaptation consideration means timing it away from training sessions is sometimes suggested, though the evidence is not strong.

One of the most extensively studied compounds here. Thousands of publications spanning toxicology, respiratory medicine, and psychiatry, including numerous randomised controlled trials.

The psychiatric literature is the most relevant to why most people in this community take it, and it is genuinely mixed rather than uniformly positive.

An approved drug for paracetamol overdose and as a mucolytic. Its status as a dietary supplement in the US has been contested by the FDA precisely because it was approved as a drug first, though enforcement discretion has been exercised and it remains widely sold.

Not on the WADA Prohibited List. Sold as a dietary supplement rather than a drug, so the S0 unapproved-substance clause does not apply. Note that supplement contamination is a recognised source of inadvertent doping violations, and third-party batch testing is the only real mitigation.

NAC is one of the few things in this library that is unambiguously proven for something — it reliably saves lives in paracetamol overdose.

The reasons most people here take it (compulsive behaviours, general antioxidant support) rest on a thinner but real evidence base, with trichotillomania the strongest of them. The doses used in those trials are higher than typical supplement labels.