N-Acetyl Cysteine and Reduced Mortality Risk

Research synthesisModerate evidenceLarge effect7 studies · 4 beneficial · 3 neutral · 0 harmful

Across 7 studies, 4 reported beneficial effects of N-acetyl cysteine (NAC) on mortality reduction, with large effect sizes observed in meta-analyses of COVID-19 patients, rodenticide poisoning, and non-acetaminophen-induced acute liver injury. Three studies found no significant effect in different populations (esophageal atresia, acetaminophen overdose) or were narrative reviews. The predominant effect size is large, and the strongest evidence comes from critically ill clinical populations.

Studied populations: hospitalized patients with COVID-19, rodenticide poisoning, and non-acetaminophen-induced acute liver injury

Caveats: The beneficial effect is derived from meta-analyses of small trials with moderate heterogeneity (I² 62–67%). Neutral results in other populations suggest the effect may be context-dependent. Doses and treatment durations were not consistently reported, limiting dose-response conclusions. The evidence base is small (7 studies) and further research is needed to confirm efficacy in broader populations.

Generated Jul 14, 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

7 of 7 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
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)

N-Acetyl Cysteine and Reduced Mortality Risk

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.

Effect of N-Acetylcysteine on mortality in COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

N-Acetyl Cysteine in Rodenticide Poisoning: A Systematic Review and Meta-Analysis.

N-acetyl cysteine versus standard of care for non-acetaminophen induced acute liver injury: a systematic review and meta-analysis.

Evaluation of nebulized N-acetyl cysteine in outcome of esophageal atresia with tracheoesophegeal fistula.

The therapeutic potential of N-acetylcysteine across multiple organ systems: a narrative review.

N-Acetylcysteine Dose and Treatment Duration in High-Risk Acetaminophen Ingestions Treated Within Eight Hours: A Retrospective Cohort Study.