N-Acetyl Cysteine and Reduced Mortality Risk

Research synthesisLow evidenceMixed effect size8 studies · 4 beneficial · 4 neutral · 0 harmful

Across 8 studies, half reported beneficial large effects on reduced mortality, while half found no significant effect. The beneficial effects were observed in meta-analyses of acute conditions such as COVID-19, rodenticide poisoning, and non-acetaminophen acute liver injury, with risk reductions of 41–53%. Neutral results came from studies in chronic obstructive pulmonary disease, a pediatric surgical population, and acetaminophen overdose, suggesting the mortality benefit is context-specific and not generalizable.

Studied populations: Patients with acute clinical conditions: COVID-19, rodenticide poisoning, and non-acetaminophen acute liver injury.

Caveats: Evidence is drawn from highly heterogeneous populations—benefits appear limited to acute, often inflammatory or toxicological settings and do not extend to chronic conditions like COPD or post-surgical recovery. Dosing and duration were inconsistently reported across studies, and only one trial specified a nebulized form; the lack of standardization precludes a universal dosing recommendation. The four neutral studies include a meta-analysis on COPD and a clinical trial, which may reflect genuine null effects in those contexts rather than overall inefficacy.

Generated Jul 16, 2026

Doses used in studies

Nac · mg/day: 800 (median 800, IQR 800–800) — 1 study

Safety in these studies

mechanical ventilationIncreased riskOR 3.88; CI, 1.14-13.29
the need for mechanical ventilation (OR 3.88; CI, 1.14-13.29) were significantly higher in the treatment group.
from: N-acetyl cysteine versus standard of care for non-acetaminophen induced acute liver injury
nausea and vomitingIncreased riskOR 3.99; CI, 1.42-11.19
the risk of developing nausea and vomiting (OR, 3.99; CI, 1.42-11.19) were significantly higher in the treatment group.
from: N-acetyl cysteine versus standard of care for non-acetaminophen induced acute liver injury
deathNo significant differenceSerious adverse eventno deaths
there were no transplants or deaths.
from: N-Acetylcysteine Dose and Treatment Duration in High-Risk Acetaminophen Ingestions Treated
hepatotoxicityNo significant differenceOne patient per group developed hepatotoxicity
One patient per group developed hepatotoxicity
from: N-Acetylcysteine Dose and Treatment Duration in High-Risk Acetaminophen Ingestions Treated
Overall tolerabilityReported
No specific adverse effects were observed in the study group.
from: Evaluation of nebulized N-acetyl cysteine in outcome of esophageal atresia with tracheoeso
Overall tolerabilityReported
the majority of adverse events are transient and minor.
from: N-acetyl cysteine versus standard of care for non-acetaminophen induced acute liver injury
Overall tolerabilityReported
Its safety profile is generally favorable, with mild gastrointestinal effects being the most common adverse events.
from: The therapeutic potential of N-acetylcysteine across multiple organ systems: a narrative r

8 of 8 papersPopulation:

COVID-19 clinical outcomes and N-acetylcysteine (CoViNAC study): a GRADE compliant meta-analysis of randomized controlled trials with molecular docking and dynamics simulation studies with Mpro of SARS-CoV-2.
- 2025-05-26
- Meta-Analysis · n = 1,125
- Cellular and molecular biology (Noisy-le-Grand, France) 71(5)
- - Seshadri Reddy Varikasuvu
  - Munikumar Manne
  - Subodh Kumar
  - Shiv Kumar Mudgal
  - Vikash Raj
  - Saurabh Varshney
  - Pratima Gupta
  - Ashoo Grover
  - Chanchal Goyal
  - Vanita Lal
  - Harminder Singh
  - Mona Lisa
  - Saransh Workshop Members
- PubMed: 40418545
- DOI: 10.14715/cmb/2025.71.5.13
2 Insights on
- Reduced Mortality Risk
- High evidence
NAC significantly reduced mortality (RR=0.59, 95% CI 0.39-0.88, p=0.01; I²=62%), indicating a 41% decreased risk of death.
Effect
Beneficial
Effect size
Large
Significant
Yes
Effect of N-Acetylcysteine on mortality in COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.
- 2025-07-29
- Meta-Analysis · n = 424
- Inflammopharmacology 33(8)
- - Chia Siang Kow
  - Dinesh Sangarran Ramachandram
  - Syed Shahzad Hasan
  - Kaeshaelya Thiruchelvam
- PubMed: 40728675
- DOI: 10.1007/s10787-025-01876-x
1 Insight on
- Reduced Mortality Risk
- High evidence
- Clinical
The pooled OR for mortality was 0.49 (95% CI: 0.25-0.94; I² = 67%), indicating a 51% reduction in the odds of death among patients receiving NAC.
Effect
Beneficial
Effect size
Large
Significant
Yes
Dose
varied by dose and route
N-Acetyl Cysteine in Rodenticide Poisoning: A Systematic Review and Meta-Analysis.
- 2022-11
- Meta-Analysis · n = 492
- Current reviews in clinical and experimental pharmacology 17(3)
- - Muhammed Rashid
  - Viji Pulikkel Chandran
  - Sreedharan Nair
  - Deepa Sudalai Muthu
  - Jemima Pappuraj
  - Krupa Ann Jacob
  - Balaji Sridhar
  - Karen Mark
  - Shabnam Hyder
  - Sohil Khan
  - Girish Thunga
- PubMed: 34455951
- DOI: 10.2174/2772432816666210825102726
4 Insights on
- Reduced Mortality Risk
- High evidence
Metaanalysis of RCTs (OR: 0.25; 95% CI: 0.11-0.59; n=2) and retrospective studies (OR: 0.34; 95% CI: 0.15-0.78; n=3) showed a significant reduction in mortality
Effect
Beneficial
Effect size
Large
Significant
Yes
Efficacy and safety of mucolytics in patients with stable chronic obstructive pulmonary disease: A systematic review and meta-analysis.
- 2024-11
- Meta-Analysis
- Respiratory investigation 62(6)
- - Hiroshi Ohnishi
  - Takuya Tanimoto
  - Ryunosuke Inaba
  - Masamitsu Eitoku
- PubMed: 39413571
- DOI: 10.1016/j.resinv.2024.10.004
11 Insights on
- Reduced Mortality Risk
- High evidence
- Clinical
Mucolytics did not improve mortality
Effect
Neutral
Effect size
Small
Significant
No
N-acetyl cysteine versus standard of care for non-acetaminophen induced acute liver injury: a systematic review and meta-analysis.
- 2021-09
- Meta-Analysis · n = 11
- Annals of hepatology 24
- - Dhan Bahadur Shrestha
  - Pravash Budhathoki
  - Yub Raj Sedhai
  - Anurag Adhikari
  - Ayusha Poudel
  - Barun Aryal
  - Ramkaji Baniya
- PubMed: 33722689
- DOI: 10.1016/j.aohep.2021.100340
3 Insights on
- Reduced Mortality Risk
- High evidence
- Clinical
Use of NAC in non-acetaminophen induced ALI showed 53% reduction in mortality compared to standard of care (OR, 0.47; CI, 0.29-0.75)
Effect
Beneficial
Effect size
Moderate
Significant
Yes
Evaluation of nebulized N-acetyl cysteine in outcome of esophageal atresia with tracheoesophegeal fistula.
- 2020-12
- Clinical Trial · n = 30
- Journal of pediatric surgery 55(12)
- - Gurmeet Singh
  - Anand Pandey
  - Gaurav Shandilya
  - Archika Gupta
  - J D Rawat
  - Ashish Wakhlu
  - S N Kureel
- PubMed: 32467034
- DOI: 10.1016/j.jpedsurg.2020.04.013
3 Insights on
- Reduced Mortality Risk
- High evidence
- Clinical
There was no significant (p = 0.41) difference in mortality between the groups.
Effect
Neutral
Effect size
Small
Significant
No
Dose
2 mL of 10% NAC, nebulized (2:5 dilution, every six hourly)
The therapeutic potential of N-acetylcysteine across multiple organ systems: a narrative review.
- 2026-07-01
- Review
- La Clinica terapeutica 177(4)
- - Teresa Joy
  - Chandana Bhargavi
  - Kishan Kadur
  - Priyanka Mehta
  - Y Lakshmisha Rao
  - Richard M Millis
  - Sunidhi Nahata
- PubMed: 42340796
- DOI: 10.7417/ct.2026.2089
7 Insights on
- Reduced Mortality Risk
- Low evidence
large-scale trials report mixed impacts on mortality
Effect
Neutral
Effect size
Small
Significant
No
N-Acetylcysteine Dose and Treatment Duration in High-Risk Acetaminophen Ingestions Treated Within Eight Hours: A Retrospective Cohort Study.
- 2026-03-19
- Observational
- Journal of medical toxicology : official journal of the American College of Medical Toxicology 22(2)
- - C James Watson
  - Michael D Simpson
  - Nishita Saraiya
  - Christopher A Wilkosz
  - Michael B Yu
  - Michele M Burns
  - Mark J Neavyn
  - Karen E Simone
  - Tania D Strout
- PubMed: 41857443
- DOI: 10.1007/s13181-026-01129-5
8 Insights on
- Reduced Mortality Risk
- Low evidence
- Clinical
One patient per group developed hepatotoxicity; there were no transplants or deaths.
Effect
Neutral
Effect size
Small
Significant
No
Dose
high dose (HD-NAC) vs standard dose (S-NAC)