N-Acetyl Cysteine and Reduced Tumor Necrosis Factor Alpha

Research synthesisLow evidenceSmall effect4 studies · 1 beneficial · 3 neutral · 0 harmful

Across 4 studies, only 1 reported a small beneficial effect of N-acetyl cysteine (NAC) on reducing tumor necrosis factor alpha (TNF-α), observed in patients with nonalcoholic steatohepatitis (NASH) at a dose of 1200 mg twice daily for 26 weeks; the remaining 3 studies (including a meta-analysis) found no significant effect. The median study duration was 119 days (approximately 17 weeks) among the 2 studies that reported duration. Overall, the evidence predominantly shows neutral effects.

Studied populations: patients with nonalcoholic steatohepatitis (NASH) (single study); other populations (general, older adults with vitamin D deficiency) showed no effect

Caveats: Many of the included studies did not reach statistical significance — effect may be smaller than the predominant direction suggests. The evidence base is small (only 4 studies), so conclusions should be considered preliminary. The only significant beneficial finding comes from a single RCT in a specific clinical population (NASH); generalizability is uncertain. No specific form of NAC was consistently reported across studies.

Generated Jun 12, 2026

Doses used in studies

mg/day: 600–2,400 (median 1,500, IQR 1,050–1,950) — 2 studies

Time to effect

Median: 4 months · IQR 2.9 months–5 months · Range 8 weeks–6.1 months — Reported in 2 of 4 studies

Safety in these studies

Overall tolerabilityReported
Group 2 has substantial improvement in various metabolic parameters and health-related quality of life with accepted safety profile parameters.
from: New Approach Combination-Dosed Therapy for Nonalcoholic Steatohepatitis Versus Vitamin E:

4 of 4 papersPopulation:

New Approach Combination-Dosed Therapy for Nonalcoholic Steatohepatitis Versus Vitamin E: A Randomized Controlled Trial.
- 2025-08
- RCT · n = 45
- Clinical therapeutics 47(8)
- - Amr Y Zakaria
  - Rehab Badawi
  - Hasnaa Osama
  - Mona A Abdelrahman
  - Asmaa M El-Kalaawy
- PubMed: 40480879
- DOI: 10.1016/j.clinthera.2025.05.006
13 Insights on
- Reduced Tumor Necrosis Factor Alpha
- High evidence
- Clinical
Group 2 exhibited substantial reductions in mean levels of all biological markers: ... tumor necrosis factor-α by 9.64% (P < 0.05)
Effect
Beneficial
Effect size
Small
Significant
Yes
Dose
1200 mg twice daily
The impact of N-acetylcysteine on lactate, biomarkers of oxidative stress, immune response, and muscle damage: A systematic review and meta-analysis.
- 2024-12
- Meta-Analysis · n = 20
- Journal of cellular and molecular medicine 28(23)
- - Marcin Sadowski
  - Emilia Zawieja
  - Agata Chmurzynska
- PubMed: 39632267
- DOI: 10.1111/jcmm.70198
8 Insights on
- Reduced Tumor Necrosis Factor Alpha
- High evidence
However, we saw no significant effect of NAC on TNF-α
Effect
Neutral
Effect size
Small
Significant
No
Co-administration of vitamin D and N-acetylcysteine to modulate immunosenescence in older adults with vitamin D deficiency: a randomized clinical trial.
- 2025-05-12
- RCT
- Frontiers in immunology 16
- - Samira Rastgoo
  - Katayoun Pourvali
  - Seyed Ahmad Raeissadat
  - Ghazaleh Eslamian
  - Hamid Zand
- PubMed: 40421021
- DOI: 10.3389/fimmu.2025.1570441
6 Insights on
- Reduced Tumor Necrosis Factor Alpha
- High evidence
- Clinical
No significant differences were observed between the groups in serum ... (no serum TNF-α reported; if not measured, then exclude). Given the ambiguity, I will only include outcomes explicitly measured. The abstract states: "No significant differences were observed between the groups in serum IL-6, C-reactive protein (CRP), or the neutrophil-to-lymphocyte ratio (NLR)". TNF-α was only measured at gene expression level, not serum. So I will not infer a neutral serum TNF-α outcome.
Effect
Neutral
Effect size
Small
Significant
No
Dose
600 mg daily
N-Acetyl-L-cysteine in human rheumatoid arthritis and its effects on nitric oxide (NO) and malondialdehyde (MDA): analytical and clinical considerations.
- 2022-07-13
- Review
- Amino acids 54(9)
- - Dimitrios Tsikas
  - Marie Mikuteit
- PubMed: 35829920
- DOI: 10.1007/s00726-022-03185-x
5 Insights on
- Reduced Tumor Necrosis Factor Alpha
- Low evidence
Reported data on NO, MDA and clinical parameters, including C-reactive protein, interleukins and tumour necrosis factor α, are contradictory in the literature.
Effect
Neutral
Effect size
Small
Significant
No

N-Acetyl Cysteine and Reduced Tumor Necrosis Factor Alpha

New Approach Combination-Dosed Therapy for Nonalcoholic Steatohepatitis Versus Vitamin E: A Randomized Controlled Trial.

The impact of N-acetylcysteine on lactate, biomarkers of oxidative stress, immune response, and muscle damage: A systematic review and meta-analysis.

Co-administration of vitamin D and N-acetylcysteine to modulate immunosenescence in older adults with vitamin D deficiency: a randomized clinical trial.

N-Acetyl-L-cysteine in human rheumatoid arthritis and its effects on nitric oxide (NO) and malondialdehyde (MDA): analytical and clinical considerations.