Anti-Neuroinflammatory Properties of n-3 Fatty Acids and Nano- Curcumin on Migraine Patients from Cellular to Clinical Insight: A Randomized, Double-Blind and Placebo-Controlled Trial

Endocr Metab Immune Disord Drug Targets. 2021;21(2):365-373. doi: 10.2174/1871530320666200729144430.


Background and objectives: Migraine is an exhausting neuro-inflammatory disorder recognized as recurrent headache attacks. Evidence has shown that Interleukin (IL)-1β plays a substantial role in the neuro-immunity pathogenicity of migraine. n-3 fatty acids and curcumin revealed neuromodulatory and anti-inflammatory effects through several pathways, of which the suppression of IL-1β gene expression is an important inflammatory pathway. The aim of this study was the investigation of synergistic relation of n -3 fatty acids and nano-curcumin on IL-1β gene expression and serum levels in migraine patients.

Methods: This study was performed as a randomized, double-blind, placebo-controlled trial in a period of two months. A total of 80 episodic migraines were assigned into 4 groups of 1) n-3 fatty acids and curcumin combination; 2) n -3 fatty acids; 3) nano-curcumin; and 4) n-3 fatty acids and curcumin placebo. The gene expression and serum level of IL-1β were measured by real-time PCR and ELISA methods respectively, at the beginning and the end of the interventions.

Results: Results showed the n-3 fatty acids and nano-curcumin combination significantly reduced the attack frequency in a synergistic status (P < 0.001). A significantly greater reduction in the serum level of IL-1β was observed in the combination group, and the differences in the other groups were not statistically significant. The IL-1β gene expression in the combination group showed a significant reduction for other treatment groups (P < 0.05), but these significant differences were absent after multiple testing Bonferroni corrections.

Conclusion: Present findings revealed that n -3 fatty acids and curcumin co-supplementation can be suggested as a promising new approach in migraine headache management, but further studies are needed to confirm these findings.

Keywords: IL-1β; Migraine; gene expression; n-3 fatty acids; nano-curcumin; randomized clinical trial.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Combined Modality Therapy / methods
  • Curcumin / administration & dosage*
  • Dietary Supplements
  • Double-Blind Method
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / blood
  • Male
  • Middle Aged
  • Migraine Disorders / blood
  • Migraine Disorders / diagnosis
  • Migraine Disorders / therapy*
  • Nanoparticles / administration & dosage*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Fatty Acids, Omega-3
  • Inflammation Mediators
  • Curcumin