N-acetylcysteine

updated

N-acetylcysteine (NAC) has been an FDA-approved drug since 1963 and is the labeled antidote for acetaminophen overdose, although the randomized evidence is low quality. Sellers market it for liver support alongside oral steroids, and a PubMed search on 9 October 2026 found no human trial of that use; the only steroid-specific study is in rats.

Cysteine prodrug and glutathione precursor

  • FDA first approved acetylcysteine as MUCOMYST on 14 September 1963; ACETADOTE (intravenous) followed under NDA 021539 on 23 January 2004.
  • A Cochrane review of 11 trials (700 participants) of paracetamol overdose treatments rated the evidence low or very low quality at high risk of bias, and said practice rests mainly on observational studies.
  • FDA's August 2022 guidance says NAC is excluded from the dietary supplement definition, and that FDA intends to exercise enforcement discretion for NAC products labeled as supplements that would otherwise be lawful.
  • In PANTHEON (1006 patients with COPD, 1 year), exacerbations were 1.16 versus 1.49 per patient-year; BRONCUS (523 patients) and a 2-year trial in 968 patients found no benefit.
  • A PubMed search on 9 October 2026 for NAC with anabolic or androgenic steroids and liver terms returned 48 records; none was a human trial. The only steroid-specific study is in 24 rats given nandrolone.
  • In a 36-person crossover, performance gains appeared only in people with low blood glutathione.

What is N-acetylcysteine approved to do?

FDA first approved acetylcysteine as a drug in 1963. It is labeled as an acetaminophen overdose antidote and, as an inhaled solution, for thick mucus. FDA's 2022 guidance treats NAC as excluded from the supplement definition while it exercises enforcement discretion for products labeled as supplements.

ACETADOTE, the intravenous product, is labeled to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen, in adults and children weighing 5 kg or more. Acetylcysteine solution 10% and 20% is labeled as adjuvant therapy for abnormal, viscid or inspissated mucous secretions in chronic and acute bronchopulmonary disease, cystic fibrosis complications and tracheostomy care, and, given orally, as an acetaminophen antidote. The mucolytic label covers inhaled solution, not oral supplement capsules.

FDA first approved acetylcysteine as MUCOMYST inhalation and oral solution under NDA 013601 on 14 September 1963; that product is now listed as discontinued, and generic solutions followed from 30 August 1994. ACETADOTE was approved under NDA 021539 on 23 January 2004, and CETYLEV effervescent tablets under NDA 207916 on 29 January 2016 (now discontinued).

FDA's August 2022 final guidance states that NAC is excluded from the dietary supplement definition because it was approved as a new drug before it was marketed as a supplement or food, and FDA denied two citizen petitions asking it to conclude otherwise. Unless it identifies safety concerns, FDA said it intends to exercise enforcement discretion for NAC products labeled as dietary supplements that would otherwise be lawful, until it completes rulemaking to allow NAC in supplements or denies the pending request. The guidance says it does not convert NAC into a drug. A Federal Register search on 9 October 2026 found no later FDA notice or rule on NAC supplement status. Current status beyond the 2022 guidance is not established here.

N-acetyl-L-cysteine (acetylcysteine) is C5H9NO3S (163.20 g/mol, CAS 616-91-1). N-acetylcysteine amide (NACA) is a different molecule and is not covered on this page.

ACETADOTE label, version effective 30 April 2025: indication, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ACETADOTE (acetylcysteine) injection, 200 mg/mL, for intravenous use, prescribing information, label version effective 30 April 2025. Set ID 472f158a-5ab9-4308-8e49-1116e6ea3d39.

The label approves ACETADOTE to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen, in adults and children weighing 5 kg or more, after acute ingestion or repeated supratherapeutic ingestion. It is contraindicated after a previous hypersensitivity reaction to acetylcysteine and warns of fatal or life-threatening anaphylaxis and of fluid overload that can cause hyponatremia, seizure and death. In a loading-rate study in Australia, 17% of patients had an acute hypersensitivity reaction (18% with a 15-minute and 14% with a 60-minute loading infusion). After a single intravenous dose, total acetylcysteine had a mean terminal half-life of 5.6 hours, clearance of 0.11 L/hr/kg (about 30% renal), a steady-state volume of distribution of 0.47 L/kg, and 66 to 87% protein binding. The label says acetylcysteine is postulated to form cysteine, which is further metabolized to glutathione.

Participants / model
Adults and children weighing 5 kg or more after acetaminophen overdose; label PK participants
Treatment
ACETADOTE acetylcysteine injection, 200 mg/mL, intravenous
Follow-up
Label version effective 30 April 2025
Study design
FDA prescribing information
Funding
not stated in the source

This is the intravenous antidote label. It does not cover oral supplement capsules, and this page gives no regimen from it.

Read the original source
Acetylcysteine solution label, version effective 22 May 2026: mucolytic and oral antidote uses

Official label

DailyMed, U.S. National Library of Medicine. Acetylcysteine solution, 10% and 20%, for inhalation or oral use, prescribing information, label version effective 22 May 2026. Set ID 5558a5f5-e821-473b-7d8a-5d33d09f0586.

The label approves acetylcysteine solution as adjuvant therapy for abnormal, viscid or inspissated mucous secretions in chronic and acute bronchopulmonary disease, pulmonary complications of cystic fibrosis, tracheostomy care and related conditions, and, given orally, as an antidote to prevent or lessen hepatic injury after a potentially hepatotoxic acetaminophen ingestion. Inhaled use can cause bronchospasm, and asthmatics should be watched carefully. Oral use at antidote doses may cause nausea, vomiting and other gastrointestinal symptoms. The mucolytic label covers inhaled solution, not oral supplement capsules.

Participants / model
Patients with bronchopulmonary mucus disorders; patients after acetaminophen overdose
Treatment
Acetylcysteine 10% and 20% solution, by inhalation or diluted orally
Follow-up
Label version effective 22 May 2026
Study design
Official label
Funding
not stated in the source

The gastrointestinal effects are label-level at antidote doses. No regimen from the label is given on this page.

Read the original source
Drugs@FDA: MUCOMYST 1963, ACETADOTE 2004, CETYLEV 2016

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 013601 (MUCOMYST), with NDA 021539 (ACETADOTE) and NDA 207916 (CETYLEV). Dates read from the openFDA Drugs@FDA records.

FDA first approved acetylcysteine as MUCOMYST inhalation and oral solution under NDA 013601 on 14 September 1963; that product is now listed as discontinued, and generic solutions followed under ANDAs from 30 August 1994. ACETADOTE (intravenous) was approved under NDA 021539 on 23 January 2004, and CETYLEV effervescent tablets under NDA 207916 on 29 January 2016 (now discontinued).

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1963 to 2016
Study design
FDA application records
Funding
not stated in the source

These records give approval dates and status. Indications come from the product labels.

Read the original source
FDA guidance, August 2022: NAC excluded from supplement definition, enforcement discretion

Regulatory record

U.S. Food and Drug Administration. Policy Regarding N-acetyl-L-cysteine: Guidance for Industry; Availability. Federal Register, 2 August 2022 (docket FDA-2022-D-0490). U.S. Government Publishing Office, govinfo.gov.

FDA's August 2022 final guidance states that FDA determined NAC is excluded from the dietary supplement definition under section 201(ff)(3)(B)(i) of the FD&C Act because it was approved as a new drug before it was marketed as a dietary supplement or food, and that FDA denied two citizen petitions asking it to conclude otherwise. FDA said that, unless it identifies safety concerns, it intends to exercise enforcement discretion for NAC products labeled as dietary supplements that would otherwise be lawful, until it either completes rulemaking to allow NAC in supplements or denies the pending rulemaking request. The guidance says it does not convert NAC into a drug. A Federal Register API search run on 9 October 2026 for NAC terms published after 2 August 2022 found no later FDA notice or rule on NAC supplement status.

Participants / model
Not a clinical population
Treatment
NAC products labeled as dietary supplements
Follow-up
Guidance of 2 August 2022
Study design
Official Federal Register notice
Funding
not stated in the source

Current status beyond the 2022 guidance is not established here.

Read the original source
PubChem: N-acetylcysteine identity

Chemical identity record

National Library of Medicine. PubChem compound record CID 12035 (N-acetyl-L-cysteine, acetylcysteine).

N-acetyl-L-cysteine (acetylcysteine): C5H9NO3S, 163.20 g/mol, CAS 616-91-1. N-acetylcysteine amide (NACA), a related compound with a similar name, is a different molecule (CID 10176265, C5H10N2O2S, 162.21 g/mol, CAS 38520-57-9) and is not covered by any other source on this page.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

What did the studies in people with liver injury find?

For acetaminophen overdose, the randomized evidence is low quality and practice rests mainly on observational studies. In established liver failure from other drugs, results were mixed, and no study tests prevention of steroid-related liver injury.

A Cochrane review found 11 randomized trials (700 participants) of interventions for paracetamol overdose, all at high risk of bias, with low or very low quality evidence. Acetylcysteine appeared superior to placebo and had fewer adverse effects than dimercaprol or cysteamine. One small trial found it may reduce mortality in fulminant hepatic failure (Peto OR 0.29, 95% CI 0.09 to 0.94). The authors conclude acetylcysteine should be given to people at risk of toxicity, and that current worldwide practice rests mainly on observational studies.

A systematic review of NAC for liver injury from drugs other than paracetamol found one randomized trial, in non-acetaminophen acute liver failure. Overall 3-week survival did not differ (70% on NAC, n=81, versus 66% on placebo, n=92), and transplant-free survival was higher (40% versus 27%). In the drug-induced subgroup, transplant-free survival was 58% (n=19) versus 27% (n=26), OR 0.27 (95% CI 0.076 to 0.942), with similar overall survival. The authors say the evidence does not allow firm conclusions. This is treatment of established liver failure, not prevention.

In a double-blind trial of 102 hospitalized adults in South Africa with anti-tuberculosis drug-induced liver injury (53 NAC, 49 placebo; 87% HIV positive), intravenous NAC did not shorten time to ALT below 100 U/L (median 7.5 versus 8 days) but shortened median time to discharge (9 versus 18 days; HR 1.73, 95% CI 1.13 to 2.65). Mortality was 14% overall and did not differ by arm.

Cochrane review: 11 trials, 700 participants, low-quality evidence

Systematic review and meta-analysis

Chiew AL et al. Cochrane Database Syst Rev. 2018;2(2):CD003328. PMID 29473717.

The review found 11 randomized trials (700 participants) of interventions for paracetamol overdose, all at high risk of bias, with low or very low quality evidence. Acetylcysteine appeared superior to placebo and had fewer adverse effects than dimercaprol or cysteamine. One small trial found it may reduce mortality in fulminant hepatic failure (Peto OR 0.29, 95% CI 0.09 to 0.94). The authors conclude acetylcysteine should be given to people at risk of toxicity, and that current worldwide practice rests mainly on observational studies.

Participants / model
People after paracetamol overdose; mostly adults
Treatment
Oral or intravenous acetylcysteine, among other interventions
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 11 randomized trials
Funding
not stated in the source

The randomized evidence is low quality and practice rests mainly on observational studies.

Read the original source
Review: one randomized trial in non-acetaminophen acute liver failure

Systematic review and meta-analysis

Chughlay MF et al. Br J Clin Pharmacol. 2016;81(6):1021-9. PMID 26757427.

The review found one randomized trial, in non-acetaminophen acute liver failure. Overall 3-week survival did not differ (70% on NAC, n=81, versus 66% on placebo, n=92), and transplant-free survival was higher (40% versus 27%). In the drug-induced subgroup, transplant-free survival was 58% (n=19) versus 27% (n=26), OR 0.27 (95% CI 0.076 to 0.942), with similar overall survival. The authors say the evidence does not allow firm conclusions.

Participants / model
Patients with non-acetaminophen acute liver failure, including a drug-induced subgroup
Treatment
Intravenous NAC infusion
Follow-up
3-week survival
Study design
Systematic review that found one randomized trial
Funding
not stated in the source

This is treatment of established liver failure, not prevention.

Read the original source
Anti-tuberculosis liver injury: 102 adults, discharge sooner, ALT recovery not faster

Randomized controlled trial

Moosa MS et al. Clin Infect Dis. 2021;73(9):e3377-e3383. PMID 32845997.

Intravenous NAC did not shorten time to ALT below 100 U/L (median 7.5 versus 8 days) but shortened median time to discharge (9 versus 18 days; HR 1.73, 95% CI 1.13 to 2.65). Mortality was 14% overall and did not differ by arm. The infusion was stopped early for an adverse reaction in 5 NAC recipients, including 1 anaphylaxis.

Participants / model
102 hospitalized adults in South Africa with anti-tuberculosis drug-induced liver injury (53 NAC, 49 placebo; 87% HIV positive)
Treatment
Intravenous NAC versus placebo
Follow-up
Hospital stay
Study design
Double-blind randomized trial
Funding
not stated in the source

Applies to hospitalized adults with established liver injury, most with HIV.

Read the original source

What did the COPD studies find?

One large trial in China cut COPD exacerbations over 1 year, while BRONCUS and a 2-year trial in China found no benefit. The respiratory record is mixed.

PANTHEON randomized 1006 patients aged 40 to 80 with moderate-to-severe COPD at 34 hospitals in China to NAC 600 mg twice daily or placebo for 1 year. Exacerbations were 1.16 versus 1.49 per patient-year (risk ratio 0.78, 95% CI 0.67 to 0.90). Adverse events occurred in 29% versus 26%. It was funded by Hainan Zambon Pharmaceutical.

BRONCUS randomized 523 patients with COPD at 50 centres to NAC 600 mg daily or placebo for 3 years. Yearly FEV1 decline (54 versus 47 mL) and exacerbations per year (1.25 versus 1.29; HR 0.99, 95% CI 0.89 to 1.10) did not differ between arms, and the authors concluded NAC was ineffective at preventing lung-function decline and exacerbations.

A 2-year trial in 968 patients aged 40 to 80 with mild-to-moderate COPD in China found NAC 600 mg twice daily did not significantly reduce total exacerbations (0.65 versus 0.72 per patient-year; RR 0.90, 95% CI 0.80 to 1.02) or change pre-bronchodilator FEV1 at 24 months.

PANTHEON: 1006 patients with COPD, 1 year, exacerbations 1.16 versus 1.49

Randomized controlled trial

Zheng JP et al. Lancet Respir Med. 2014;2(3):187-94. PMID 24621680.

Exacerbations were 1.16 versus 1.49 per patient-year (risk ratio 0.78, 95% CI 0.67 to 0.90). Adverse events occurred in 29% versus 26%.

Participants / model
1006 patients aged 40 to 80 with moderate-to-severe COPD at 34 hospitals in China
Treatment
Oral NAC 600 mg tablets twice daily versus placebo
Follow-up
1 year
Study design
Randomized placebo-controlled trial
Funding
Hainan Zambon Pharmaceutical

Funded by Hainan Zambon Pharmaceutical.

Read the original source
BRONCUS: 523 patients with COPD, 3 years, no benefit

Randomized controlled trial

Decramer M et al. Lancet. 2005;365(9470):1552-60. PMID 15866309.

Yearly FEV1 decline (54 versus 47 mL) and exacerbations per year (1.25 versus 1.29; HR 0.99, 95% CI 0.89 to 1.10) did not differ between arms. The authors concluded NAC was ineffective at preventing lung-function decline and exacerbations.

Participants / model
523 patients with COPD at 50 centres
Treatment
Oral NAC 600 mg daily versus placebo
Follow-up
3 years
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Applies to patients with COPD.

Read the original source
Two-year COPD trial: 968 patients, no significant reduction in exacerbations

Randomized controlled trial

Zhou Y et al. Nat Commun. 2024;15(1):8468. PMID 39349461.

NAC did not significantly reduce total exacerbations (0.65 versus 0.72 per patient-year; RR 0.90, 95% CI 0.80 to 1.02) or change pre-bronchodilator FEV1 at 24 months.

Participants / model
968 patients aged 40 to 80 with mild-to-moderate COPD in China
Treatment
Oral NAC 600 mg twice daily versus placebo
Follow-up
2 years
Study design
Randomized trial
Funding
not stated in the source

Applies to patients with mild-to-moderate COPD.

Read the original source

Does NAC protect the liver during oral steroid use?

No human trial tests it. A PubMed search on 9 October 2026 returned 48 records, and none was a human trial of NAC for preventing or treating steroid-related liver injury. The only steroid-specific study is in 24 rats given nandrolone.

Sellers market NAC as an antioxidant and glutathione precursor for liver support alongside hepatotoxic oral steroids, for general oxidative stress, and for occasional respiratory or mucolytic use. The 48 PubMed records were reviews, acetaminophen and other drug-toxicity studies, mechanistic, cell and animal studies, case reports, and one rat study. The liver-support use during steroid cycles has no trial behind it in those records.

The rat study gave 24 male Wistar rats nandrolone decanoate 10 mg/kg for 6 weeks. Adding NAC 150 mg/kg daily partially reduced the nandrolone-related rises in AST, ALT, ALP and blood lipids, and reduced liver fibrosis and related gene and protein changes. Routes were not stated in the abstract. It is rat evidence with nandrolone, not evidence in people or with the oral steroids sellers name.

The nearest human evidence is treatment of established liver failure and anti-tuberculosis drug liver injury, not prevention. The mucolytic label covers inhaled solution, not oral supplement capsules.

PubMed search, 9 October 2026: 48 records, none a human trial

PubMed search record

PubMed search run on 9 October 2026: acetylcysteine AND (anabolic steroid OR anabolic-androgenic OR androgenic steroid OR oxandrolone OR methyltestosterone OR stanozolol OR oxymetholone OR methandienone) AND (liver OR hepat* OR cholesta* OR jaundice). 48 records returned.

The search returned 48 records. None was a human trial of NAC for preventing or treating steroid-related liver injury. The records were reviews, acetaminophen and other drug-toxicity studies, mechanistic, cell and animal studies, case reports, and the rat nandrolone study. The liver-support-on-cycle use has no trial behind it in the records reviewed.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
Rat study: 24 male Wistar rats, nandrolone with NAC

Animal study

Mohammadpour-Asl S et al. J Steroid Biochem Mol Biol. 2026;256:106902. PMID 41242401.

In 24 male Wistar rats given nandrolone decanoate 10 mg/kg for 6 weeks, adding NAC 150 mg/kg daily partially reduced the nandrolone-related rises in AST, ALT, ALP and blood lipids and reduced liver fibrosis and related gene and protein changes.

Participants / model
24 male Wistar rats
Treatment
Nandrolone decanoate with NAC; routes not stated in the abstract
Follow-up
6 weeks
Study design
Randomized animal experiment
Funding
not stated in the source

This is the only steroid-specific NAC liver study found. It is rat evidence with nandrolone, not evidence in people or with the oral steroids the supplier names.

Read the original source
Review: one randomized trial in non-acetaminophen acute liver failure

Systematic review and meta-analysis

Chughlay MF et al. Br J Clin Pharmacol. 2016;81(6):1021-9. PMID 26757427.

The review found one randomized trial, in non-acetaminophen acute liver failure. Overall 3-week survival did not differ (70% on NAC, n=81, versus 66% on placebo, n=92), and transplant-free survival was higher (40% versus 27%). In the drug-induced subgroup, transplant-free survival was 58% (n=19) versus 27% (n=26), OR 0.27 (95% CI 0.076 to 0.942), with similar overall survival. The authors say the evidence does not allow firm conclusions.

Participants / model
Patients with non-acetaminophen acute liver failure, including a drug-induced subgroup
Treatment
Intravenous NAC infusion
Follow-up
3-week survival
Study design
Systematic review that found one randomized trial
Funding
not stated in the source

This is treatment of established liver failure, not prevention.

Read the original source
Anti-tuberculosis liver injury: 102 adults, discharge sooner, ALT recovery not faster

Randomized controlled trial

Moosa MS et al. Clin Infect Dis. 2021;73(9):e3377-e3383. PMID 32845997.

Intravenous NAC did not shorten time to ALT below 100 U/L (median 7.5 versus 8 days) but shortened median time to discharge (9 versus 18 days; HR 1.73, 95% CI 1.13 to 2.65). Mortality was 14% overall and did not differ by arm. The infusion was stopped early for an adverse reaction in 5 NAC recipients, including 1 anaphylaxis.

Participants / model
102 hospitalized adults in South Africa with anti-tuberculosis drug-induced liver injury (53 NAC, 49 placebo; 87% HIV positive)
Treatment
Intravenous NAC versus placebo
Follow-up
Hospital stay
Study design
Double-blind randomized trial
Funding
not stated in the source

Applies to hospitalized adults with established liver injury, most with HIV.

Read the original source
Acetylcysteine solution label, version effective 22 May 2026: mucolytic and oral antidote uses

Official label

DailyMed, U.S. National Library of Medicine. Acetylcysteine solution, 10% and 20%, for inhalation or oral use, prescribing information, label version effective 22 May 2026. Set ID 5558a5f5-e821-473b-7d8a-5d33d09f0586.

The label approves acetylcysteine solution as adjuvant therapy for abnormal, viscid or inspissated mucous secretions in chronic and acute bronchopulmonary disease, pulmonary complications of cystic fibrosis, tracheostomy care and related conditions, and, given orally, as an antidote to prevent or lessen hepatic injury after a potentially hepatotoxic acetaminophen ingestion. Inhaled use can cause bronchospasm, and asthmatics should be watched carefully. Oral use at antidote doses may cause nausea, vomiting and other gastrointestinal symptoms. The mucolytic label covers inhaled solution, not oral supplement capsules.

Participants / model
Patients with bronchopulmonary mucus disorders; patients after acetaminophen overdose
Treatment
Acetylcysteine 10% and 20% solution, by inhalation or diluted orally
Follow-up
Label version effective 22 May 2026
Study design
Official label
Funding
not stated in the source

The gastrointestinal effects are label-level at antidote doses. No regimen from the label is given on this page.

Read the original source

Does NAC help people with normal glutathione levels?

In one small crossover, gains appeared only in people with low blood glutathione. Performance and oxidative stress did not change in people with moderate or high glutathione.

From 100 screened people, 36 were grouped by low, moderate or high blood glutathione (12 per group) and given NAC or placebo for 30 days in a double-blind crossover. Only the low-glutathione group responded: glutathione was restored, systemic oxidative stress fell, and VO2max, time-trial and Wingate performance rose 13.6%, 15.4% and 11.4%. Performance and redox state did not change in the moderate and high groups.

This supports a deficiency-dependent effect, not a general antioxidant benefit. The dose wording in the abstract is ambiguous, so no dose is given here.

Glutathione-stratified crossover: 36 people, gains only with low glutathione

Randomized controlled trial

Paschalis V et al. Free Radic Biol Med. 2018;115:288-297. PMID 29233792.

Only the low-glutathione group responded: glutathione was restored, systemic oxidative stress fell, and VO2max, time-trial and Wingate performance rose 13.6%, 15.4% and 11.4%. Performance and redox state did not change in the moderate and high groups.

Participants / model
36 people selected from 100 screened by low, moderate or high blood glutathione (12 per group)
Treatment
NAC supplementation versus placebo; the dose wording in the abstract is ambiguous, so no dose is given here
Follow-up
30 days
Study design
Double-blind randomized crossover trial
Funding
not stated in the source

This supports a deficiency-dependent effect, not a general antioxidant benefit.

Read the original source

How does NAC work, and what does the body do with it?

The label says acetylcysteine is postulated to form cysteine, which is further metabolized to glutathione. Oral bioavailability is low, and total NAC has a terminal half-life of about 6 hours.

The ACETADOTE label says acetylcysteine is postulated to form cysteine, which is further metabolized to glutathione. The glutathione-precursor mechanism is label-supported, but in the one trial that stratified by baseline level, glutathione was restored only in people who started low.

After a single intravenous dose, the label gives total acetylcysteine a mean terminal half-life of 5.6 hours, clearance of 0.11 L/hr/kg (about 30% renal), a steady-state volume of distribution of 0.47 L/kg and 66 to 87% protein binding. In 6 healthy volunteers, oral bioavailability was 4.0% for reduced NAC and 9.1% for total NAC. Total NAC had a terminal half-life of 5.58 hours after intravenous and 6.25 hours after oral dosing, and reduced NAC 1.95 hours after intravenous dosing.

ACETADOTE label, version effective 30 April 2025: indication, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ACETADOTE (acetylcysteine) injection, 200 mg/mL, for intravenous use, prescribing information, label version effective 30 April 2025. Set ID 472f158a-5ab9-4308-8e49-1116e6ea3d39.

The label approves ACETADOTE to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen, in adults and children weighing 5 kg or more, after acute ingestion or repeated supratherapeutic ingestion. It is contraindicated after a previous hypersensitivity reaction to acetylcysteine and warns of fatal or life-threatening anaphylaxis and of fluid overload that can cause hyponatremia, seizure and death. In a loading-rate study in Australia, 17% of patients had an acute hypersensitivity reaction (18% with a 15-minute and 14% with a 60-minute loading infusion). After a single intravenous dose, total acetylcysteine had a mean terminal half-life of 5.6 hours, clearance of 0.11 L/hr/kg (about 30% renal), a steady-state volume of distribution of 0.47 L/kg, and 66 to 87% protein binding. The label says acetylcysteine is postulated to form cysteine, which is further metabolized to glutathione.

Participants / model
Adults and children weighing 5 kg or more after acetaminophen overdose; label PK participants
Treatment
ACETADOTE acetylcysteine injection, 200 mg/mL, intravenous
Follow-up
Label version effective 30 April 2025
Study design
FDA prescribing information
Funding
not stated in the source

This is the intravenous antidote label. It does not cover oral supplement capsules, and this page gives no regimen from it.

Read the original source
PK crossover: 6 healthy volunteers, oral bioavailability 4.0% reduced and 9.1% total NAC

Human study

Olsson B et al. Eur J Clin Pharmacol. 1988;34(1):77-82. PMID 3360052.

Oral bioavailability was 4.0% for reduced NAC and 9.1% for total NAC. Total NAC had a terminal half-life of 5.58 hours after intravenous and 6.25 hours after oral dosing. Reduced NAC had a terminal half-life of 1.95 hours after intravenous dosing.

Participants / model
6 healthy volunteers
Treatment
Single doses, NAC 200 mg intravenous and 400 mg oral, in a randomized crossover
Follow-up
Single doses
Study design
Randomized crossover pharmacokinetic study
Funding
not stated in the source

A single study in 6 volunteers.

Read the original source
Glutathione-stratified crossover: 36 people, gains only with low glutathione

Randomized controlled trial

Paschalis V et al. Free Radic Biol Med. 2018;115:288-297. PMID 29233792.

Only the low-glutathione group responded: glutathione was restored, systemic oxidative stress fell, and VO2max, time-trial and Wingate performance rose 13.6%, 15.4% and 11.4%. Performance and redox state did not change in the moderate and high groups.

Participants / model
36 people selected from 100 screened by low, moderate or high blood glutathione (12 per group)
Treatment
NAC supplementation versus placebo; the dose wording in the abstract is ambiguous, so no dose is given here
Follow-up
30 days
Study design
Double-blind randomized crossover trial
Funding
not stated in the source

This supports a deficiency-dependent effect, not a general antioxidant benefit.

Read the original source

What warnings and side effects are reported?

The ACETADOTE label contraindicates use after a prior hypersensitivity reaction and warns of fatal or life-threatening anaphylaxis and of fluid overload. Inhaled use can cause bronchospasm, and oral antidote doses may cause nausea and vomiting.

The ACETADOTE label contraindicates use after a previous hypersensitivity reaction to acetylcysteine. It warns of fatal or life-threatening anaphylaxis and of fluid overload that can cause hyponatremia, seizure and death. In a loading-rate study in Australia, 17% of patients had an acute hypersensitivity reaction (18% with a 15-minute and 14% with a 60-minute loading infusion).

The solution label notes that inhaled use can cause bronchospasm, so asthmatics should be watched carefully, and that oral use at antidote doses may cause nausea, vomiting and other gastrointestinal symptoms. These effects are label-level at antidote doses.

In PANTHEON, adverse events occurred in 29% on NAC versus 26% on placebo. In the anti-tuberculosis liver injury trial, the infusion was stopped early for an adverse reaction in 5 NAC recipients, including 1 anaphylaxis. No source reviewed gives adverse-event rates at typical supplement doses.

ACETADOTE label, version effective 30 April 2025: indication, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ACETADOTE (acetylcysteine) injection, 200 mg/mL, for intravenous use, prescribing information, label version effective 30 April 2025. Set ID 472f158a-5ab9-4308-8e49-1116e6ea3d39.

The label approves ACETADOTE to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen, in adults and children weighing 5 kg or more, after acute ingestion or repeated supratherapeutic ingestion. It is contraindicated after a previous hypersensitivity reaction to acetylcysteine and warns of fatal or life-threatening anaphylaxis and of fluid overload that can cause hyponatremia, seizure and death. In a loading-rate study in Australia, 17% of patients had an acute hypersensitivity reaction (18% with a 15-minute and 14% with a 60-minute loading infusion). After a single intravenous dose, total acetylcysteine had a mean terminal half-life of 5.6 hours, clearance of 0.11 L/hr/kg (about 30% renal), a steady-state volume of distribution of 0.47 L/kg, and 66 to 87% protein binding. The label says acetylcysteine is postulated to form cysteine, which is further metabolized to glutathione.

Participants / model
Adults and children weighing 5 kg or more after acetaminophen overdose; label PK participants
Treatment
ACETADOTE acetylcysteine injection, 200 mg/mL, intravenous
Follow-up
Label version effective 30 April 2025
Study design
FDA prescribing information
Funding
not stated in the source

This is the intravenous antidote label. It does not cover oral supplement capsules, and this page gives no regimen from it.

Read the original source
Acetylcysteine solution label, version effective 22 May 2026: mucolytic and oral antidote uses

Official label

DailyMed, U.S. National Library of Medicine. Acetylcysteine solution, 10% and 20%, for inhalation or oral use, prescribing information, label version effective 22 May 2026. Set ID 5558a5f5-e821-473b-7d8a-5d33d09f0586.

The label approves acetylcysteine solution as adjuvant therapy for abnormal, viscid or inspissated mucous secretions in chronic and acute bronchopulmonary disease, pulmonary complications of cystic fibrosis, tracheostomy care and related conditions, and, given orally, as an antidote to prevent or lessen hepatic injury after a potentially hepatotoxic acetaminophen ingestion. Inhaled use can cause bronchospasm, and asthmatics should be watched carefully. Oral use at antidote doses may cause nausea, vomiting and other gastrointestinal symptoms. The mucolytic label covers inhaled solution, not oral supplement capsules.

Participants / model
Patients with bronchopulmonary mucus disorders; patients after acetaminophen overdose
Treatment
Acetylcysteine 10% and 20% solution, by inhalation or diluted orally
Follow-up
Label version effective 22 May 2026
Study design
Official label
Funding
not stated in the source

The gastrointestinal effects are label-level at antidote doses. No regimen from the label is given on this page.

Read the original source
PANTHEON: 1006 patients with COPD, 1 year, exacerbations 1.16 versus 1.49

Randomized controlled trial

Zheng JP et al. Lancet Respir Med. 2014;2(3):187-94. PMID 24621680.

Exacerbations were 1.16 versus 1.49 per patient-year (risk ratio 0.78, 95% CI 0.67 to 0.90). Adverse events occurred in 29% versus 26%.

Participants / model
1006 patients aged 40 to 80 with moderate-to-severe COPD at 34 hospitals in China
Treatment
Oral NAC 600 mg tablets twice daily versus placebo
Follow-up
1 year
Study design
Randomized placebo-controlled trial
Funding
Hainan Zambon Pharmaceutical

Funded by Hainan Zambon Pharmaceutical.

Read the original source
Anti-tuberculosis liver injury: 102 adults, discharge sooner, ALT recovery not faster

Randomized controlled trial

Moosa MS et al. Clin Infect Dis. 2021;73(9):e3377-e3383. PMID 32845997.

Intravenous NAC did not shorten time to ALT below 100 U/L (median 7.5 versus 8 days) but shortened median time to discharge (9 versus 18 days; HR 1.73, 95% CI 1.13 to 2.65). Mortality was 14% overall and did not differ by arm. The infusion was stopped early for an adverse reaction in 5 NAC recipients, including 1 anaphylaxis.

Participants / model
102 hospitalized adults in South Africa with anti-tuberculosis drug-induced liver injury (53 NAC, 49 placebo; 87% HIV positive)
Treatment
Intravenous NAC versus placebo
Follow-up
Hospital stay
Study design
Double-blind randomized trial
Funding
not stated in the source

Applies to hospitalized adults with established liver injury, most with HIV.

Read the original source

Why does NAC sit in A tier?

An approval since 1963 and a labeled antidote use support the A, though the randomized evidence behind the antidote use is low quality. The supplier's liver-support-on-steroids use has no human trial.

Acetylcysteine has been an FDA-approved drug since 1963 and is the labeled antidote for acetaminophen overdose, although a Cochrane review rated the randomized evidence low quality and said practice rests mainly on observational data. The respiratory record is mixed: one large trial cut COPD exacerbations and two others found no benefit.

The supplier's headline use, liver protection during oral steroid cycles, sits outside every label and has no human trial in the records reviewed. The nearest human evidence is treatment of acute liver failure and anti-tuberculosis drug injury, and the only steroid-specific study is in rats. The general antioxidant claim held only for people with low glutathione in one small trial.

ACETADOTE label, version effective 30 April 2025: indication, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ACETADOTE (acetylcysteine) injection, 200 mg/mL, for intravenous use, prescribing information, label version effective 30 April 2025. Set ID 472f158a-5ab9-4308-8e49-1116e6ea3d39.

The label approves ACETADOTE to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen, in adults and children weighing 5 kg or more, after acute ingestion or repeated supratherapeutic ingestion. It is contraindicated after a previous hypersensitivity reaction to acetylcysteine and warns of fatal or life-threatening anaphylaxis and of fluid overload that can cause hyponatremia, seizure and death. In a loading-rate study in Australia, 17% of patients had an acute hypersensitivity reaction (18% with a 15-minute and 14% with a 60-minute loading infusion). After a single intravenous dose, total acetylcysteine had a mean terminal half-life of 5.6 hours, clearance of 0.11 L/hr/kg (about 30% renal), a steady-state volume of distribution of 0.47 L/kg, and 66 to 87% protein binding. The label says acetylcysteine is postulated to form cysteine, which is further metabolized to glutathione.

Participants / model
Adults and children weighing 5 kg or more after acetaminophen overdose; label PK participants
Treatment
ACETADOTE acetylcysteine injection, 200 mg/mL, intravenous
Follow-up
Label version effective 30 April 2025
Study design
FDA prescribing information
Funding
not stated in the source

This is the intravenous antidote label. It does not cover oral supplement capsules, and this page gives no regimen from it.

Read the original source
Cochrane review: 11 trials, 700 participants, low-quality evidence

Systematic review and meta-analysis

Chiew AL et al. Cochrane Database Syst Rev. 2018;2(2):CD003328. PMID 29473717.

The review found 11 randomized trials (700 participants) of interventions for paracetamol overdose, all at high risk of bias, with low or very low quality evidence. Acetylcysteine appeared superior to placebo and had fewer adverse effects than dimercaprol or cysteamine. One small trial found it may reduce mortality in fulminant hepatic failure (Peto OR 0.29, 95% CI 0.09 to 0.94). The authors conclude acetylcysteine should be given to people at risk of toxicity, and that current worldwide practice rests mainly on observational studies.

Participants / model
People after paracetamol overdose; mostly adults
Treatment
Oral or intravenous acetylcysteine, among other interventions
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 11 randomized trials
Funding
not stated in the source

The randomized evidence is low quality and practice rests mainly on observational studies.

Read the original source
PANTHEON: 1006 patients with COPD, 1 year, exacerbations 1.16 versus 1.49

Randomized controlled trial

Zheng JP et al. Lancet Respir Med. 2014;2(3):187-94. PMID 24621680.

Exacerbations were 1.16 versus 1.49 per patient-year (risk ratio 0.78, 95% CI 0.67 to 0.90). Adverse events occurred in 29% versus 26%.

Participants / model
1006 patients aged 40 to 80 with moderate-to-severe COPD at 34 hospitals in China
Treatment
Oral NAC 600 mg tablets twice daily versus placebo
Follow-up
1 year
Study design
Randomized placebo-controlled trial
Funding
Hainan Zambon Pharmaceutical

Funded by Hainan Zambon Pharmaceutical.

Read the original source
BRONCUS: 523 patients with COPD, 3 years, no benefit

Randomized controlled trial

Decramer M et al. Lancet. 2005;365(9470):1552-60. PMID 15866309.

Yearly FEV1 decline (54 versus 47 mL) and exacerbations per year (1.25 versus 1.29; HR 0.99, 95% CI 0.89 to 1.10) did not differ between arms. The authors concluded NAC was ineffective at preventing lung-function decline and exacerbations.

Participants / model
523 patients with COPD at 50 centres
Treatment
Oral NAC 600 mg daily versus placebo
Follow-up
3 years
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Applies to patients with COPD.

Read the original source
PubMed search, 9 October 2026: 48 records, none a human trial

PubMed search record

PubMed search run on 9 October 2026: acetylcysteine AND (anabolic steroid OR anabolic-androgenic OR androgenic steroid OR oxandrolone OR methyltestosterone OR stanozolol OR oxymetholone OR methandienone) AND (liver OR hepat* OR cholesta* OR jaundice). 48 records returned.

The search returned 48 records. None was a human trial of NAC for preventing or treating steroid-related liver injury. The records were reviews, acetaminophen and other drug-toxicity studies, mechanistic, cell and animal studies, case reports, and the rat nandrolone study. The liver-support-on-cycle use has no trial behind it in the records reviewed.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
Rat study: 24 male Wistar rats, nandrolone with NAC

Animal study

Mohammadpour-Asl S et al. J Steroid Biochem Mol Biol. 2026;256:106902. PMID 41242401.

In 24 male Wistar rats given nandrolone decanoate 10 mg/kg for 6 weeks, adding NAC 150 mg/kg daily partially reduced the nandrolone-related rises in AST, ALT, ALP and blood lipids and reduced liver fibrosis and related gene and protein changes.

Participants / model
24 male Wistar rats
Treatment
Nandrolone decanoate with NAC; routes not stated in the abstract
Follow-up
6 weeks
Study design
Randomized animal experiment
Funding
not stated in the source

This is the only steroid-specific NAC liver study found. It is rat evidence with nandrolone, not evidence in people or with the oral steroids the supplier names.

Read the original source
Glutathione-stratified crossover: 36 people, gains only with low glutathione

Randomized controlled trial

Paschalis V et al. Free Radic Biol Med. 2018;115:288-297. PMID 29233792.

Only the low-glutathione group responded: glutathione was restored, systemic oxidative stress fell, and VO2max, time-trial and Wingate performance rose 13.6%, 15.4% and 11.4%. Performance and redox state did not change in the moderate and high groups.

Participants / model
36 people selected from 100 screened by low, moderate or high blood glutathione (12 per group)
Treatment
NAC supplementation versus placebo; the dose wording in the abstract is ambiguous, so no dose is given here
Follow-up
30 days
Study design
Double-blind randomized crossover trial
Funding
not stated in the source

This supports a deficiency-dependent effect, not a general antioxidant benefit.

Read the original source

Studies and sources

PubChem: N-acetylcysteine identity

Chemical identity record

National Library of Medicine. PubChem compound record CID 12035 (N-acetyl-L-cysteine, acetylcysteine).

N-acetyl-L-cysteine (acetylcysteine): C5H9NO3S, 163.20 g/mol, CAS 616-91-1. N-acetylcysteine amide (NACA), a related compound with a similar name, is a different molecule (CID 10176265, C5H10N2O2S, 162.21 g/mol, CAS 38520-57-9) and is not covered by any other source on this page.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source
ACETADOTE label, version effective 30 April 2025: indication, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. ACETADOTE (acetylcysteine) injection, 200 mg/mL, for intravenous use, prescribing information, label version effective 30 April 2025. Set ID 472f158a-5ab9-4308-8e49-1116e6ea3d39.

The label approves ACETADOTE to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen, in adults and children weighing 5 kg or more, after acute ingestion or repeated supratherapeutic ingestion. It is contraindicated after a previous hypersensitivity reaction to acetylcysteine and warns of fatal or life-threatening anaphylaxis and of fluid overload that can cause hyponatremia, seizure and death. In a loading-rate study in Australia, 17% of patients had an acute hypersensitivity reaction (18% with a 15-minute and 14% with a 60-minute loading infusion). After a single intravenous dose, total acetylcysteine had a mean terminal half-life of 5.6 hours, clearance of 0.11 L/hr/kg (about 30% renal), a steady-state volume of distribution of 0.47 L/kg, and 66 to 87% protein binding. The label says acetylcysteine is postulated to form cysteine, which is further metabolized to glutathione.

Participants / model
Adults and children weighing 5 kg or more after acetaminophen overdose; label PK participants
Treatment
ACETADOTE acetylcysteine injection, 200 mg/mL, intravenous
Follow-up
Label version effective 30 April 2025
Study design
FDA prescribing information
Funding
not stated in the source

This is the intravenous antidote label. It does not cover oral supplement capsules, and this page gives no regimen from it.

Read the original source
Acetylcysteine solution label, version effective 22 May 2026: mucolytic and oral antidote uses

Official label

DailyMed, U.S. National Library of Medicine. Acetylcysteine solution, 10% and 20%, for inhalation or oral use, prescribing information, label version effective 22 May 2026. Set ID 5558a5f5-e821-473b-7d8a-5d33d09f0586.

The label approves acetylcysteine solution as adjuvant therapy for abnormal, viscid or inspissated mucous secretions in chronic and acute bronchopulmonary disease, pulmonary complications of cystic fibrosis, tracheostomy care and related conditions, and, given orally, as an antidote to prevent or lessen hepatic injury after a potentially hepatotoxic acetaminophen ingestion. Inhaled use can cause bronchospasm, and asthmatics should be watched carefully. Oral use at antidote doses may cause nausea, vomiting and other gastrointestinal symptoms. The mucolytic label covers inhaled solution, not oral supplement capsules.

Participants / model
Patients with bronchopulmonary mucus disorders; patients after acetaminophen overdose
Treatment
Acetylcysteine 10% and 20% solution, by inhalation or diluted orally
Follow-up
Label version effective 22 May 2026
Study design
Official label
Funding
not stated in the source

The gastrointestinal effects are label-level at antidote doses. No regimen from the label is given on this page.

Read the original source
Drugs@FDA: MUCOMYST 1963, ACETADOTE 2004, CETYLEV 2016

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 013601 (MUCOMYST), with NDA 021539 (ACETADOTE) and NDA 207916 (CETYLEV). Dates read from the openFDA Drugs@FDA records.

FDA first approved acetylcysteine as MUCOMYST inhalation and oral solution under NDA 013601 on 14 September 1963; that product is now listed as discontinued, and generic solutions followed under ANDAs from 30 August 1994. ACETADOTE (intravenous) was approved under NDA 021539 on 23 January 2004, and CETYLEV effervescent tablets under NDA 207916 on 29 January 2016 (now discontinued).

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1963 to 2016
Study design
FDA application records
Funding
not stated in the source

These records give approval dates and status. Indications come from the product labels.

Read the original source
FDA guidance, August 2022: NAC excluded from supplement definition, enforcement discretion

Regulatory record

U.S. Food and Drug Administration. Policy Regarding N-acetyl-L-cysteine: Guidance for Industry; Availability. Federal Register, 2 August 2022 (docket FDA-2022-D-0490). U.S. Government Publishing Office, govinfo.gov.

FDA's August 2022 final guidance states that FDA determined NAC is excluded from the dietary supplement definition under section 201(ff)(3)(B)(i) of the FD&C Act because it was approved as a new drug before it was marketed as a dietary supplement or food, and that FDA denied two citizen petitions asking it to conclude otherwise. FDA said that, unless it identifies safety concerns, it intends to exercise enforcement discretion for NAC products labeled as dietary supplements that would otherwise be lawful, until it either completes rulemaking to allow NAC in supplements or denies the pending rulemaking request. The guidance says it does not convert NAC into a drug. A Federal Register API search run on 9 October 2026 for NAC terms published after 2 August 2022 found no later FDA notice or rule on NAC supplement status.

Participants / model
Not a clinical population
Treatment
NAC products labeled as dietary supplements
Follow-up
Guidance of 2 August 2022
Study design
Official Federal Register notice
Funding
not stated in the source

Current status beyond the 2022 guidance is not established here.

Read the original source
Cochrane review: 11 trials, 700 participants, low-quality evidence

Systematic review and meta-analysis

Chiew AL et al. Cochrane Database Syst Rev. 2018;2(2):CD003328. PMID 29473717.

The review found 11 randomized trials (700 participants) of interventions for paracetamol overdose, all at high risk of bias, with low or very low quality evidence. Acetylcysteine appeared superior to placebo and had fewer adverse effects than dimercaprol or cysteamine. One small trial found it may reduce mortality in fulminant hepatic failure (Peto OR 0.29, 95% CI 0.09 to 0.94). The authors conclude acetylcysteine should be given to people at risk of toxicity, and that current worldwide practice rests mainly on observational studies.

Participants / model
People after paracetamol overdose; mostly adults
Treatment
Oral or intravenous acetylcysteine, among other interventions
Follow-up
Varied by included trial
Study design
Systematic review and meta-analysis of 11 randomized trials
Funding
not stated in the source

The randomized evidence is low quality and practice rests mainly on observational studies.

Read the original source
Review: one randomized trial in non-acetaminophen acute liver failure

Systematic review and meta-analysis

Chughlay MF et al. Br J Clin Pharmacol. 2016;81(6):1021-9. PMID 26757427.

The review found one randomized trial, in non-acetaminophen acute liver failure. Overall 3-week survival did not differ (70% on NAC, n=81, versus 66% on placebo, n=92), and transplant-free survival was higher (40% versus 27%). In the drug-induced subgroup, transplant-free survival was 58% (n=19) versus 27% (n=26), OR 0.27 (95% CI 0.076 to 0.942), with similar overall survival. The authors say the evidence does not allow firm conclusions.

Participants / model
Patients with non-acetaminophen acute liver failure, including a drug-induced subgroup
Treatment
Intravenous NAC infusion
Follow-up
3-week survival
Study design
Systematic review that found one randomized trial
Funding
not stated in the source

This is treatment of established liver failure, not prevention.

Read the original source
Anti-tuberculosis liver injury: 102 adults, discharge sooner, ALT recovery not faster

Randomized controlled trial

Moosa MS et al. Clin Infect Dis. 2021;73(9):e3377-e3383. PMID 32845997.

Intravenous NAC did not shorten time to ALT below 100 U/L (median 7.5 versus 8 days) but shortened median time to discharge (9 versus 18 days; HR 1.73, 95% CI 1.13 to 2.65). Mortality was 14% overall and did not differ by arm. The infusion was stopped early for an adverse reaction in 5 NAC recipients, including 1 anaphylaxis.

Participants / model
102 hospitalized adults in South Africa with anti-tuberculosis drug-induced liver injury (53 NAC, 49 placebo; 87% HIV positive)
Treatment
Intravenous NAC versus placebo
Follow-up
Hospital stay
Study design
Double-blind randomized trial
Funding
not stated in the source

Applies to hospitalized adults with established liver injury, most with HIV.

Read the original source
Rat study: 24 male Wistar rats, nandrolone with NAC

Animal study

Mohammadpour-Asl S et al. J Steroid Biochem Mol Biol. 2026;256:106902. PMID 41242401.

In 24 male Wistar rats given nandrolone decanoate 10 mg/kg for 6 weeks, adding NAC 150 mg/kg daily partially reduced the nandrolone-related rises in AST, ALT, ALP and blood lipids and reduced liver fibrosis and related gene and protein changes.

Participants / model
24 male Wistar rats
Treatment
Nandrolone decanoate with NAC; routes not stated in the abstract
Follow-up
6 weeks
Study design
Randomized animal experiment
Funding
not stated in the source

This is the only steroid-specific NAC liver study found. It is rat evidence with nandrolone, not evidence in people or with the oral steroids the supplier names.

Read the original source
PK crossover: 6 healthy volunteers, oral bioavailability 4.0% reduced and 9.1% total NAC

Human study

Olsson B et al. Eur J Clin Pharmacol. 1988;34(1):77-82. PMID 3360052.

Oral bioavailability was 4.0% for reduced NAC and 9.1% for total NAC. Total NAC had a terminal half-life of 5.58 hours after intravenous and 6.25 hours after oral dosing. Reduced NAC had a terminal half-life of 1.95 hours after intravenous dosing.

Participants / model
6 healthy volunteers
Treatment
Single doses, NAC 200 mg intravenous and 400 mg oral, in a randomized crossover
Follow-up
Single doses
Study design
Randomized crossover pharmacokinetic study
Funding
not stated in the source

A single study in 6 volunteers.

Read the original source
Glutathione-stratified crossover: 36 people, gains only with low glutathione

Randomized controlled trial

Paschalis V et al. Free Radic Biol Med. 2018;115:288-297. PMID 29233792.

Only the low-glutathione group responded: glutathione was restored, systemic oxidative stress fell, and VO2max, time-trial and Wingate performance rose 13.6%, 15.4% and 11.4%. Performance and redox state did not change in the moderate and high groups.

Participants / model
36 people selected from 100 screened by low, moderate or high blood glutathione (12 per group)
Treatment
NAC supplementation versus placebo; the dose wording in the abstract is ambiguous, so no dose is given here
Follow-up
30 days
Study design
Double-blind randomized crossover trial
Funding
not stated in the source

This supports a deficiency-dependent effect, not a general antioxidant benefit.

Read the original source
PANTHEON: 1006 patients with COPD, 1 year, exacerbations 1.16 versus 1.49

Randomized controlled trial

Zheng JP et al. Lancet Respir Med. 2014;2(3):187-94. PMID 24621680.

Exacerbations were 1.16 versus 1.49 per patient-year (risk ratio 0.78, 95% CI 0.67 to 0.90). Adverse events occurred in 29% versus 26%.

Participants / model
1006 patients aged 40 to 80 with moderate-to-severe COPD at 34 hospitals in China
Treatment
Oral NAC 600 mg tablets twice daily versus placebo
Follow-up
1 year
Study design
Randomized placebo-controlled trial
Funding
Hainan Zambon Pharmaceutical

Funded by Hainan Zambon Pharmaceutical.

Read the original source
BRONCUS: 523 patients with COPD, 3 years, no benefit

Randomized controlled trial

Decramer M et al. Lancet. 2005;365(9470):1552-60. PMID 15866309.

Yearly FEV1 decline (54 versus 47 mL) and exacerbations per year (1.25 versus 1.29; HR 0.99, 95% CI 0.89 to 1.10) did not differ between arms. The authors concluded NAC was ineffective at preventing lung-function decline and exacerbations.

Participants / model
523 patients with COPD at 50 centres
Treatment
Oral NAC 600 mg daily versus placebo
Follow-up
3 years
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Applies to patients with COPD.

Read the original source
Two-year COPD trial: 968 patients, no significant reduction in exacerbations

Randomized controlled trial

Zhou Y et al. Nat Commun. 2024;15(1):8468. PMID 39349461.

NAC did not significantly reduce total exacerbations (0.65 versus 0.72 per patient-year; RR 0.90, 95% CI 0.80 to 1.02) or change pre-bronchodilator FEV1 at 24 months.

Participants / model
968 patients aged 40 to 80 with mild-to-moderate COPD in China
Treatment
Oral NAC 600 mg twice daily versus placebo
Follow-up
2 years
Study design
Randomized trial
Funding
not stated in the source

Applies to patients with mild-to-moderate COPD.

Read the original source

Why is N-acetylcysteine in A tier?

A fits a drug approved since 1963 for narrow uses and sold for much wider ones. The antidote label stands on low-quality randomized evidence, the COPD results are mixed, and the headline supplement use, liver protection alongside oral steroids, has no human trial.