N-acetylcysteine (NAC, generic name acetylcysteine) is the N-acetyl form of the amino acid L-cysteine. It is an FDA-approved prescription drug with two labeled uses: an antidote that prevents or lessens liver injury after an acetaminophen (paracetamol) overdose, and an inhaled mucolytic (a drug that thins mucus). It is also widely sold as a supplement, marketed mainly as a cysteine source for the body’s own glutathione.
The single most important regulatory fact is unusual: because NAC was approved as a drug in 1963, before anyone sold it as a supplement, FDA has concluded that it is legally excluded from the definition of a dietary supplement. Since 2022, FDA has said it will not act against otherwise lawful NAC supplements on that basis while it considers a rule (FDA guidance, 2022).
This page summarizes what the FDA labels, clinical trials and FDA’s regulatory record report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Thiol (sulfur-containing) amino acid derivative; antidote and mucolytic |
| Formula / weight | C₅H₉NO₃S, 163.2 g/mol (PubChem) |
| Approved products | Acetadote IV injection (approved 2004); acetylcysteine 10% and 20% solution for inhalation or oral use (Mucomyst brand now discontinued) |
| Labeled doses | IV antidote: 300 mg/kg total over 20–21 h. Oral antidote: 140 mg/kg, then 70 mg/kg every 4 h for 17 doses. Inhaled: usually 3–5 mL of 20% solution 3–4 times daily |
| Doses in supplement-type trials | 600–2,400 mg/day orally |
| Half-life | 5.6 h for total NAC after IV dosing (Acetadote label); 6.25 h after an oral dose |
| Oral bioavailability | ≈4–10% |
| US status | Prescription drug; excluded from the dietary supplement definition, but FDA enforcement discretion for supplements since August 2022 |
| WADA status | Not named on the 2026 list; IV infusions over 100 mL per 12 hours are a prohibited method (M2.2) outside legitimate hospital care |
What it is
NAC is L-cysteine with an acetyl group attached to its amino nitrogen; its chemical name is (2R)-2-acetamido-3-sulfanylpropanoic acid (PubChem). Its activity comes from the free sulfhydryl (–SH) group of cysteine, the same group that makes glutathione work.
That group explains both approved uses (acetylcysteine solution label; Acetadote label):
| Use | How NAC is thought to work |
|---|---|
| Mucolytic | The sulfhydryl group probably breaks the disulfide bonds that cross-link mucus proteins, lowering mucus thickness. The effect increases with pH and is strongest between pH 7 and 9. |
| Acetaminophen antidote | In overdose, normal liver pathways are saturated and more acetaminophen is turned into a toxic reactive metabolite that uses up liver glutathione. NAC probably protects the liver by maintaining or restoring glutathione, or by binding the reactive metabolite directly. |
Relationship to glutathione
Glutathione is a three-amino-acid molecule (glutamate, cysteine, glycine) that cells make themselves. Cysteine supply is one of the main limits on how much they can make. NAC is deacetylated in the body to cysteine, which is then used to build glutathione (Acetadote label). This is why NAC is described as an indirect glutathione source, while glutathione supplements try to supply the finished molecule. The glutathione page covers how poorly oral glutathione itself is absorbed.
Head-to-head human data are limited. In a 3-week crossover study of 20 people with metabolic syndrome, the authors reported that a sublingual glutathione product raised blood glutathione more than either oral glutathione or NAC. Two of the four authors were affiliated with Laboratoires Le Stum, a commercial laboratory (Schmitt et al., Redox Biol 2015).
Pharmacokinetics
Only a small share of an oral dose reaches the bloodstream as NAC. Studies distinguish “reduced” NAC (the free drug) from “total” NAC (including NAC bound to proteins and other thiols):
| Source | Design | Half-life | Oral bioavailability |
|---|---|---|---|
| Acetadote label | Single IV dose | 5.6 h (total NAC) | Not applicable |
| Borgström et al., 1986 | 10 healthy adults, 600 mg IV and oral | 2.27 h (late elimination) | 6–10%, depending on tablet type |
| Olsson et al., 1988 | 6 healthy adults, 200 mg IV, 400 mg oral | Reduced NAC 1.95 h (IV); total NAC 5.58 h (IV), 6.25 h (oral) | 4.0% (reduced); 9.1% (total) |
Other label figures: volume of distribution 0.47 L/kg, protein binding 66–87%, and about 30% of clearance through the kidneys. In people with liver impairment, the half-life rose by 80% and total exposure 1.6-fold, changes the label does not consider clinically meaningful. Based on the kinetics, the label states NAC should be nearly fully cleared 30 hours after a dose.
Approved medical use
Acetaminophen overdose antidote
Acetadote is indicated to prevent or lessen liver injury after a potentially hepatotoxic amount of acetaminophen, in adults and children weighing 5 kg or more, after an acute overdose or repeated supratherapeutic ingestion (taking too much over a longer period). Whether to treat after an acute overdose is decided mainly from a blood acetaminophen level drawn at least 4 hours after ingestion and plotted on the revised Rumack-Matthew nomogram (Acetadote label).
The label gives two IV regimens, both totaling 300 mg/kg (adult weight band 41–99 kg shown; doses are capped at the 100 kg amount above that):
| Regimen | Bag 1 | Bag 2 | Bag 3 | Total time |
|---|---|---|---|---|
| Three-bag (all patients 5 kg or more) | 150 mg/kg over 1 h | 50 mg/kg over 4 h | 100 mg/kg over 16 h | 21 h |
| Two-bag (41 kg or more only) | 200 mg/kg over 4 h | 100 mg/kg over 16 h | None | 20 h |
The label notes that it is not known whether the two-bag regimen prevents liver injury as well as the three-bag regimen, but it may cause fewer hypersensitivity reactions. Timing matters most: protection is greatest when treatment starts within 8 hours, declines after that, and is limited at 15–24 hours, though treatment should not be withheld because the reported ingestion time may be wrong.
The older oral regimen uses the 20% solution diluted to 5%: 140 mg/kg as a loading dose, then 70 mg/kg every 4 hours for a total of 17 maintenance doses (acetylcysteine solution label).
Mucolytic
The inhalation solution is labeled as add-on therapy for abnormal, thick or sticky mucus in conditions including chronic bronchitis and emphysema, pneumonia, cystic fibrosis lung complications, tracheostomy care, atelectasis (collapsed lung) caused by mucus plugging and before diagnostic bronchial studies. For nebulization by face mask or mouthpiece, the usual labeled dose is 3–5 mL of the 20% solution (or 6–10 mL of the 10% solution) 3–4 times a day (acetylcysteine solution label).
The Mucomyst brand of this solution (NDA 013601) is listed by FDA as discontinued, with a determination that it was not withdrawn for safety or effectiveness reasons; generic solutions remain available (Drugs@FDA).
Regulatory status: NAC in dietary supplements
Under the Federal Food, Drug, and Cosmetic Act, a substance approved as a new drug cannot be sold as a dietary supplement unless it was marketed as a supplement or food before that approval, or unless FDA issues a regulation allowing it. NAC was approved as a new drug on September 14, 1963, and FDA states it is not aware of any earlier supplement or food use (FDA guidance, 2022). The timeline:
| Date | Event |
|---|---|
| July 2020 | In a warning letter to the seller of a “hangover” product (July 23, 2020), FDA states that it has concluded NAC products are excluded from the dietary supplement definition, even apart from the product’s disease claims (FDA warning letter) |
| June and August 2021 | The Council for Responsible Nutrition (June 1) and the Natural Products Association (August 18) file citizen petitions asking FDA to reverse that position; the NPA petition alternatively asks for a regulation allowing NAC in supplements |
| November 24, 2021 | FDA issues tentative responses and requests safety data on NAC as a supplement |
| March 31, 2022 | FDA denies the CRN petition and the NPA petition’s main request, confirming the exclusion; the NPA rulemaking request stays open |
| April 2022 | FDA issues a draft enforcement discretion guidance |
| August 2022 | FDA finalizes the guidance, “Policy Regarding N-acetyl-L-cysteine” |
| November 29, 2023 | FDA adds its systematic review of NAC safety literature to its peer review agenda (FDA constituent update) |
Under the final guidance, FDA does not intend to object to NAC products labeled as dietary supplements that would otherwise be lawful supplements. FDA explained that its initial review had not revealed safety concerns, and that NAC supplements had been sold in the US for over 30 years. The policy does not cover products that claim to diagnose, treat, cure, mitigate or prevent a disease, or products that are adulterated or misbranded for other reasons. It lasts until FDA either completes rulemaking to allow NAC in supplements or denies the NPA petition’s rulemaking request (FDA guidance, 2022). The guidance is non-binding. FDA said that if it identifies no safety concerns, it is likely to propose a rule permitting NAC in supplements; its most recent public update on the topic is the November 2023 notice above (FDA constituent update).
This is a different issue from glutathione, which is sold as a supplement ingredient and whose main FDA concern is contaminated compounded injections.
NAC is not named on the WADA Prohibited List. Intravenous infusions or injections of more than 100 mL per 12 hours are a prohibited method (M2.2) unless received during hospital treatment, surgery or clinical diagnostic investigations (WADA 2026 Prohibited List).
What the research shows
Acetaminophen overdose
NAC’s antidote role rests mainly on large case series rather than placebo-controlled trials:
| Study | Patients | Finding |
|---|---|---|
| Smilkstein et al., NEJM 1988 | 2,540 treated with the 72-hour oral regimen (US multicenter, 1976–1985) | Hepatotoxicity in 6.1% of probable-risk patients treated within 10 h vs 26.4% when treated at 10–24 h; protective regardless of acetaminophen level when started within 8 h |
| Acetadote label observational database | High-risk patients given 300 mg/kg IV | Hepatotoxicity in 2 of 53 (4%) treated within 8 h vs 21 of 48 (44%) treated after 15 h |
In the 1988 series, no deaths were clearly caused by acetaminophen among patients whose treatment began within 16 hours (Smilkstein et al., 1988).
COPD and chronic bronchitis
Oral NAC has been tested in long trials for chronic lung disease. Results depend on the trial:
| Trial | Design | Dose and duration | Result |
|---|---|---|---|
| BRONCUS (Decramer 2005) | RCT, 523 COPD patients, Europe | 600 mg/day, 3 years | No effect on lung function decline or exacerbations (HR 0.99, 95% CI 0.89–1.10) |
| PANTHEON (Zheng 2014) | RCT, 1,006 moderate-to-severe COPD patients, China | 600 mg twice daily, 1 year | 1.16 vs 1.49 exacerbations per patient-year (RR 0.78, 95% CI 0.67–0.90) |
PANTHEON was funded by Zambon, a maker of NAC. A Cochrane review of 38 trials (10,377 participants) of oral mucolytics, including NAC, found that patients were more likely to remain exacerbation-free (Peto OR 1.73, 95% CI 1.56–1.91), with about 8 people treated for 9 months to keep one more free of exacerbations. The reviewers cautioned that newer and longer trials showed smaller benefits than older ones, and found little effect on lung function or quality of life (Poole et al., Cochrane 2019).
Idiopathic pulmonary fibrosis
In the PANTHER-IPF trial, a three-drug arm (prednisone, azathioprine and NAC) was stopped for safety concerns. In the continuing comparison of 133 patients on NAC alone versus 131 on placebo, NAC did not slow the loss of lung capacity (forced vital capacity fell 0.18 vs 0.19 L over 60 weeks, p = 0.77) (Martinez et al., NEJM 2014).
Kidney protection with contrast dye
Oral NAC was widely given to protect the kidneys before angiography. The PRESERVE trial randomized 5,177 high-risk patients (4,993 analyzed) to 5 days of oral NAC or placebo. The combined outcome of death, dialysis or lasting kidney decline at 90 days occurred in 4.6% vs 4.5% (OR 1.02, 95% CI 0.78–1.33), with no difference in contrast-associated kidney injury (Weisbord et al., NEJM 2018).
Cannabis use disorder
NAC has been studied for addiction because animal research suggests it modulates glutamate signaling in the brain’s reward circuits. Results did not replicate across age groups:
- Adolescents: In an 8-week RCT of 116 people aged 15–21, NAC 1,200 mg twice daily doubled the odds of a negative urine cannabis test versus placebo (OR 2.4, 95% CI 1.1–5.2) (Gray et al., Am J Psychiatry 2012).
- Adults: In a 12-week RCT of 302 adults at the same dose, there was no difference (OR 1.00, 95% CI 0.63–1.59; 22.3% vs 22.4% negative tests) (Gray et al., Drug Alcohol Depend 2017).
Exercise and muscle
The evidence on training is small and points in two directions:
- Low-glutathione individuals: Researchers screened 100 people and selected 36 with low, moderate or high blood glutathione. In a double-blind crossover, NAC (reported as 2 × 600 mg twice daily) for 30 days improved VO₂max, time-trial and Wingate sprint performance by 13.6%, 15.4% and 11.4% only in the low-glutathione group. It did not change performance or redox status in the moderate and high groups (Paschalis et al., Free Radic Biol Med 2018).
- Recovery from muscle damage: In a crossover study, 10 men took NAC at 20 mg/kg/day or placebo after 300 eccentric (muscle-lengthening) contractions. NAC reduced markers of inflammation and early strength loss, but it also blunted the activation of muscle growth signals (Akt, mTOR and p70S6K) and of a muscle-repair factor. Performance had fully recovered at 8 days only with placebo (Michailidis et al., Am J Clin Nutr 2013).
The second study is relevant to the common idea that more antioxidant is always better: in people with normal glutathione, extra NAC may interfere with the signaling that drives repair after hard training.
Liver protection during anabolic steroid use
NAC is often promoted for “liver support” alongside oral anabolic steroids such as Anadrol or Anavar. No controlled human trials of this use were found. The data are from animals: in 24 male rats given nandrolone decanoate for 6 weeks, adding NAC (150 mg/kg daily) partly reduced the rise in liver enzymes, lipid changes and liver fibrosis (Mohammadpour-Asl et al., J Steroid Biochem Mol Biol 2026). These results cannot be assumed to apply to people. The approved antidote use concerns acetaminophen, a different mechanism of liver injury.
Side effects and risks
IV use: hypersensitivity reactions
The main risk of IV NAC is an acute hypersensitivity (anaphylactoid) reaction, usually during the loading dose. The label reports rates from a Canadian study of 4,709 adults treated between 1980 and 2005 (Acetadote label):
| Reaction (adults) | Incidence |
|---|---|
| Any hypersensitivity reaction | 8% |
| Hives or facial flushing | 6.1% |
| Itching | 4.3% |
| Respiratory symptoms (cough, wheeze, chest tightness, bronchospasm) | 1.9% |
| Swelling (edema) | 1.6% |
| Low blood pressure | 0.1% |
| Anaphylaxis | 0.1% |
In an Australian trial of 180 patients, 17% had an acute hypersensitivity reaction (18% with a 15-minute and 14% with a 60-minute loading infusion). In observational studies cited in the label, the two-bag regimen was linked with fewer reactions; for example, 4% vs 16% in three Danish hospitals. Fatal anaphylaxis has been reported after marketing. Other labeled warnings:
- Fluid overload: IV NAC can cause fluid overload leading to low sodium, seizures and death, so volumes are reduced for patients under 40 kg or on fluid restriction.
- Asthma: patients with asthma should be closely monitored.
- NAC overdose: anaphylaxis, cerebral edema (brain swelling) and hemolytic-uremic syndrome, including fatal cases, have been reported after acetylcysteine overdose.
Oral and inhaled use
Oral NAC, especially at the large antidote doses, can cause nausea, vomiting and other stomach symptoms; rash, with or without mild fever, is rare. Inhaled NAC can cause unpredictable bronchospasm (airway narrowing), even in patients who used it before without problems. Other reported effects include mouth sores (stomatitis), nausea, runny nose, drowsiness and chest tightness, along with an unpleasant smell (acetylcysteine solution label).
At supplement-range doses in a 1-year trial (1,200 mg/day), adverse events occurred in 29% of patients on NAC vs 26% on placebo (Zheng et al., 2014).
Interactions
- Nitroglycerin: NAC strengthens the blood-vessel-widening effect of nitroglycerin. In a double-blind trial in 46 patients with unstable angina, IV nitroglycerin plus IV NAC (5 g every 6 hours) caused symptomatic low blood pressure in 7 patients vs 0 with nitroglycerin alone (Horowitz et al., Circulation 1988).
- Activated charcoal: charcoal adsorbs NAC in the test tube and may reduce its effect when both are used in overdose (acetylcysteine solution label).
- Nebulizer mixtures: the solution is incompatible with some antibiotics in the same mixture, including tetracycline, oxytetracycline, erythromycin lactobionate and ampicillin.
Pregnancy and fertility
In acetaminophen overdose during pregnancy, the label warns that delaying treatment may increase risk to mother and fetus; both acetaminophen and NAC cross the placenta. Animal studies found no harm to the fetus at oral doses similar to the IV treatment dose. In female rats, a high IV dose (1,000 mg/kg/day) sharply reduced fertility, an effect not seen at 300 mg/kg/day; its relevance to people is unknown (Acetadote label).
Key takeaways
- An approved antidote first. NAC is the standard treatment to prevent liver injury after acetaminophen overdose, and it works best when started within 8 hours.
- A glutathione building block. NAC supplies cysteine, which cells use to make glutathione; it does not deliver glutathione itself, and oral bioavailability of NAC is only about 4–10%.
- A legal gray zone for supplements. FDA holds that NAC is excluded from the dietary supplement definition because it was approved as a drug in 1963, but since 2022 it has used enforcement discretion for supplements without disease claims.
- Mixed evidence outside the labels. Results were positive in one large COPD trial but negative in another, and negative in pulmonary fibrosis and contrast-dye kidney injury; a cannabis benefit in adolescents did not replicate in adults.
- Antioxidant effects can cut both ways. NAC improved performance only in people with low glutathione, and in one study it blunted muscle repair signaling after damaging exercise.
- Main risks are route-specific. IV use carries hypersensitivity reactions (about 8% of adults in a large series), inhaled use can trigger bronchospasm, and NAC can amplify the blood-pressure drop from nitroglycerin.
Sources
- National Center for Biotechnology Information. PubChem Compound Summary for CID 12035, Acetylcysteine. PubChem.
- Cumberland Pharmaceuticals. Acetadote (acetylcysteine) injection prescribing information, revised 11/2024. DailyMed.
- Hospira. Acetylcysteine solution, USP 10% and 20% prescribing information. DailyMed.
- Food and Drug Administration. Drugs@FDA: Mucomyst (acetylcysteine) solution, NDA 013601. FDA.
- Food and Drug Administration. Policy Regarding N-acetyl-L-cysteine: Guidance for Industry. August 2022. Docket FDA-2022-D-0490. FDA.
- Food and Drug Administration. FDA Releases Final Guidance on Enforcement Discretion for Certain NAC Products. Constituent update, August 1, 2022; updated November 29, 2023. FDA.
- Food and Drug Administration. Warning letter to Vita Heaven, LLC dba Hangover Heaven, MARCS-CMS 593765. July 23, 2020. FDA.
- World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA 2026 Prohibited List.
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