Effects of N-acetylcysteine supplementation on disease activity, oxidative stress, and inflammatory and metabolic parameters in rheumatoid arthritis patients: a randomized double-blind placebo-controlled trial

Amino Acids. 2022 Mar;54(3):433-440. doi: 10.1007/s00726-022-03134-8. Epub 2022 Feb 8.


Considering the importance of inflammation and oxidative stress in the development of rheumatoid arthritis (RA) as well as anti-inflammatory and antioxidant features of N-acetylcysteine (NAC), this study was conducted to evaluate the effect of NAC supplementation on disease activity, oxidative stress, and inflammatory and metabolic parameters in RA patients. In a randomized double-masked placebo-controlled trial, 74 RA subjects were chosen and randomly divided into two groups to take 600 mg of NAC or placebo twice daily for 3 months. Before and after the study, disease activity was assessed via disease activity score-28 (DAS-28), and serum malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPX) activity, nitric oxide (NO), high-sensitivity C-reactive protein (hs-CRP), fasting blood sugar (FBS), lipid profile, and erythrocyte sedimentation rate (ESR) were measured. Seventy patients completed the trial. Compared to baseline, NAC significantly reduced morning stiffness (P < 0.001), DAS-28 (P < 0.001), ESR (P = 0.004), MDA (P < 0.001), NO (P < 0.001), hs-CRP (P = 0.006), FBS (P < 0.001), and low-density lipoprotein cholesterol (LDL-C) (P = 0.023) and significantly increased GPx activity (P = 0.015) and high-density lipoprotein cholesterol (HDL-C) level (P = 0.001). After treatment, remarkable differences were only seen between the two groups in serum NO (P = 0.003), FBS (P = 0.010), and HDL-C (P < 0.001) adjusted for baseline measures. There were no significant changes in morning stiffness, DAS-28, ESR, hs-CRP, MDA, TAC, GPx activity, triglyceride, total cholesterol, and LDL-C levels compared to the placebo group. In conclusion, NAC did not improve RA disease activity, but reduced NO and FBS and increased HDL-C levels. It appears that NAC should not be consumed as a replacement for routine medications prescribed in RA therapy, but it can be used as an adjunctive therapy.

Keywords: Disease activity; Inflammation; N-Acetylcysteine; Oxidative stress; Rheumatoid arthritis.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acetylcysteine* / pharmacology
  • Acetylcysteine* / therapeutic use
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Arthritis, Rheumatoid* / drug therapy
  • Biomarkers
  • C-Reactive Protein
  • Dietary Supplements
  • Double-Blind Method
  • Humans
  • Oxidative Stress


  • Antioxidants
  • Biomarkers
  • C-Reactive Protein
  • Acetylcysteine