NAC (N-Acetylcysteine)

What is NAC and what does it do in the body?

According to the review by Deepmala and colleagues, NAC (N-acetylcysteine) is recognized for its role in acetaminophen (paracetamol) overdose and as a mucolytic. ^[4] Coles and colleagues describe NAC as a well-known antioxidant and a glutathione (GSH) precursor. ^[11] This is “role in the body” information; being a glutathione precursor does not mean that an orally taken NAC supplement increases glutathione in tissues or prevents a disease. Intravenous or oral use as a drug in hospital settings and oral use as a store-bought product are separate questions.

What is NAC used for as a drug?

Paracetamol poisoning

The FDA’s approved label for intravenous acetylcysteine injection (revised 07/2025) describes the drug as an “antidote for acetaminophen overdose”: it is indicated to prevent or reduce liver damage after ingestion of a potentially hepatotoxic quantity of acetaminophen, in adult and pediatric patients 5 kg and over who have had an acute ingestion or repeated excessive ingestion. The label describes measuring plasma or serum acetaminophen level at least 4 hours after ingestion and using a nomogram to decide on treatment, and giving a loading dose while the level is being measured when the time of ingestion is unknown; this is a treatment regimen used by physicians. It states that safety and effectiveness in pediatric patients have not been shown with adequate and well-controlled studies and that use in children 5 kg and over is based on clinical practice. The overdose section of the label says that fatal and life-threatening events, including anaphylaxis, cerebral edema, and hemolytic uremic syndrome, have been reported with acetylcysteine overdose. ^[1]

The 2018 Cochrane review covers 11 randomized studies (700 participants) in paracetamol overdose; only two comparisons could be included in the meta-analysis and all studies were at high risk of bias; evidence quality was low or very low. Acetylcysteine appeared superior to placebo; it showed fewer adverse effects than dimercaprol or cysteamine; superiority over methionine was not proven. In fulminant liver failure, acetylcysteine may have reduced death in a small study (Peto OR 0.29; 95% CI 0.09–0.94; low quality). A study was reported in which a modified 12-hour regimen with a 2-hour 100 mg/kg loading dose was associated with significantly fewer adverse reactions than the conventional three-bag 20.25-hour regimen (low quality). Because children were not included in most studies, the evidence belongs to adults only. The review states that acetylcysteine should be given to those at risk of toxicity and adds that current management rests mainly on observational studies, which show a reduction in morbidity and mortality. ^[2] This is not a supplement used at home; it is drug management of a medical emergency.

Does NAC work in COPD and chronic bronchitis?

The Cochrane review by Poole and colleagues covers 38 studies (10,377 participants) comparing mucolytic treatment lasting at least two months with placebo in adults with chronic bronchitis or COPD; mucolytics include N-acetylcysteine, carbocisteine, erdosteine, and ambroxol. In 28 studies (6,723 participants), the likelihood of remaining free of exacerbations was higher with mucolytics (Peto OR 1.73; 95% CI 1.56–1.91; moderate certainty; NNTB 8 for a mean of 9 months; heterogeneity high, I² 62%). The type or dose of mucolytic did not change the effect size; newer studies showed less benefit than older ones; effects were smaller in long studies. A reduction of 0.43 days per month in days of disability due to illness, a reduction in the number of people hospitalized (Peto OR 0.68; 4 studies; results inconsistent), and a change in quality of life that did not reach the clinical threshold (MD −1.37; 95% CI −2.85 to 0.11) were reported; the difference for death was not conclusive. The effect belongs to the mucolytic class, not specifically to NAC. ^[3]

Does NAC supplementation raise glutathione?

In the open-label study by Coles and colleagues, 5 people with Parkinson’s disease and 3 healthy controls took 6,000 mg of oral NAC per day for 28 days. Peripheral antioxidant measures (catalase and GSH/GSSG) increased; lipid peroxidation indicators (4-HNE and MDA) did not change; there was no significant increase in brain glutathione. The authors stated that they could attribute this to low oral bioavailability and small GSH/GSSG responses; 3 of the Parkinson’s patients (of 5) reported symptomatic adverse events. The study is very small and uncontrolled. ^[11]

Does NAC work in psychiatric and behavioral conditions?

The 2015 systematic review by Deepmala and colleagues found “positive evidence” for NAC in areas such as autism, Alzheimer’s, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, and schizophrenia; it reported preliminary evidence for anxiety, ADHD, and mild traumatic brain injury, and that the existing evidence does not support use for gambling, methamphetamine, and nicotine addictions and for ALS; it stated that NAC is generally safe and well tolerated and that larger controlled studies are needed for specific disorders. According to the PubMed record, the institution of one of the authors is a drug development company. ^[4] The individual studies below detail this general picture:

• Cannabis use disorder (adults): In a 12-week double-blind study of 302 people aged 18–50, 1,200 mg of NAC twice daily or placebo (all received contingency management and medical management); the proportion with negative urine cannabinoid tests was the same in the groups (22.3% versus 22.4%; OR 1.00; 95% CI 0.63–1.59). ^[5]
• Cannabis use disorder (youth, 2025): 12 weeks in 192 people aged 14–21; there was no difference in the proportion with negative urine tests (RR 0.93; 95% CI 0.53–1.64); gastrointestinal adverse events were more frequent in the NAC group (63/98 versus 37/94; p<0.001). ^[6]
• Adult trichotillomania (Grant 2009): 50 people (45 women), 12 weeks, 1,200–2,400 mg of NAC per day or placebo; greater reduction on the MGH Hairpulling Scale (P<0.001); the proportion “much or very much improved” was 56% versus 16% (P=0.003). It is a single study. ^[7]
• Child and adolescent trichotillomania (Bloch 2013): In a 12-week add-on treatment study in 39 children aged 8–17, there was no difference in any primary or secondary measure; the response rate was 25% with NAC and 21% in the placebo group. ^[8]
• Obsessive-compulsive disorder (add-on to SSRI): In 6 RCTs (195 patients), borderline benefit in Y-BOCS total with 5–8 weeks of use (p=0.05); no difference with use shorter than 5 weeks and longer than 12 weeks; no difference in obsession and compulsion subscores; no difference in adverse events. ^[9]

In Deepmala’s 2015 assessment, cannabis addiction was in the positive section, whereas no benefit was found in the two subsequent large RCTs (2017 adult, 2025 youth); the authors of the 2025 study note that the earlier positive results were obtained together with a strong behavioral platform (contingency management). ^[6]

Is NAC effective in reproductive health and PCOS?

The meta-analysis by Thakker and colleagues pooled 8 studies covering 910 women with polycystic ovary syndrome (selection, performance, and attrition bias in two studies; high risk of reporting bias in four studies). In women taking NAC, the likelihood of live birth, pregnancy, and ovulation was higher compared with placebo; the likelihood of pregnancy and ovulation was lower compared with metformin. There was no difference from placebo for miscarriage, menstrual regulation, acne, hirsutism, adverse events, BMI, testosterone, and insulin. The authors state that the findings need to be confirmed with well-designed RCTs and with outcomes such as live birth rate, with longer follow-up. ^[10]

Is NAC safe?

Deepmala’s review describes NAC as generally safe and well tolerated. ^[4] Even so, with oral use, gastrointestinal side effects were markedly more frequent in the NAC group than with placebo in youth (63/98 versus 37/94). ^[6] At very high amounts (6,000 mg per day, 28 days), 3 of 5 Parkinson’s patients reported symptomatic adverse events. ^[11] The FDA’s 2022 guidance states that the FDA’s initial review of the use of NAC as a dietary supplement did not identify a safety concern; the full safety review is ongoing. ^[12] For pregnancy and breastfeeding, the label (intravenous drug) states that limited published case reports are not sufficient to establish the associated drug risk and that there are no data on its presence in human milk; delaying treatment of a paracetamol overdose can increase morbidity and mortality for the mother and fetus. ^[1]

Legal status of NAC in the US and Türkiye

United States

The FDA has determined that NAC is excluded from the dietary supplement definition because NAC was approved as a new drug on September 14, 1963 and no evidence could be found that it was marketed as a supplement or food before that. On March 31, 2022, the FDA denied two petition requests for NAC to be considered a supplement, but stated that it was considering rulemaking that would allow NAC to be used as a supplement. The guidance states that the FDA will follow an enforcement discretion policy for some NAC products labeled as supplements (those not intended to diagnose, treat, or prevent disease); this policy is valid until rulemaking is completed or the petition is denied. ^[12]

Türkiye

In Türkiye, food supplements are under the regulation of the Ministry of Agriculture and Forestry, and Ministry approval is mandatory for every food supplement to be placed on the market. ^[14] In the Ministry’s Restricted Substances List (last updated September 21, 2026), the N-acetyl-L-cysteine row reads: “Its use as an active ingredient in food supplements has not been found appropriate.” (publication date March 8, 2016). ^[13] This list is only for food supplements; the use of NAC as a drug is subject to separate legislation, and this page does not give treatment or drug use instructions.

Evidence table: claim, population, and limits