Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis

Arch Med Res. 2018 Aug;49(6):391-398. doi: 10.1016/j.arcmed.2018.12.004. Epub 2018 Dec 27.


Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the central nervous system (CNS). Neuroinflammation and oxidative stress are involved in the pathogenesis of MS, promoting tissue damage and demielinization. Current research findings suggest that melatonin has antioxidant and neuroprotective effects. The aim of this study was to evaluate the efficacy of melatonin on serum pro-inflammatory cytokines and oxidative stress markers in relapsing-remitting multiple sclerosis (RRMS). 36 patients diagnose with RRMS treated with Interferon β-1b (IFNβ-1b) were enrolled in a double bind, randomized, placebo controlled trial. The experimental group received orally 25 mg/d of melatonin for 6 months. After melatonin administration, we observed a significant decrease in serum concentration of pro-inflammatory cytokines and oxidative stress markers; 18% for TNF-α (p <0.05), 34.8% for IL-1β (p <0.05), 34.7% for IL-6 (p <0.05), 39.9% for lipoperoxides (LPO) (p <0.05) and 24% for nitric oxide catabolites (NOC) levels (p <0.05), compared with placebo group. No significant difference in clinical efficacy outcomes were found between groups. Melatonin treatment was well tolerated and we did not observe significant differences in rates of side effects between the two groups. We concluded that melatonin administration during 6 months period is effective in reducing levels of serum pro-inflammatory cytokines and oxidative stress markers in patients with RRMS. These data support future studies evaluating the safety and effectiveness of melatonin supplementation in RRMS patients.

Keywords: Depression; Melatonin; Multiple sclerosis; Oxidative stress; pro-inflammatory cytokines.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antioxidants / therapeutic use*
  • Biomarkers / metabolism
  • Cytokines / blood*
  • Double-Blind Method
  • Female
  • Humans
  • Interferon-beta / therapeutic use
  • Interleukin-1beta / blood
  • Interleukin-1beta / metabolism
  • Interleukin-6 / blood
  • Lipid Peroxides / blood
  • Male
  • Melatonin / adverse effects
  • Melatonin / therapeutic use*
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Neuroprotective Agents / therapeutic use*
  • Nitric Oxide
  • Oxidative Stress / drug effects*
  • Tumor Necrosis Factor-alpha / blood


  • Antioxidants
  • Biomarkers
  • Cytokines
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Lipid Peroxides
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Interferon-beta
  • Melatonin