The Neuromodulatory Effects of ω-3 Fatty Acids and Nano-Curcumin on the COX-2/ iNOS Network in Migraines: A Clinical Trial Study from Gene Expression to Clinical Symptoms

Endocr Metab Immune Disord Drug Targets. 2019;19(6):874-884. doi: 10.2174/1871530319666190212170140.


Background: Migraine is a common neuroinflammatory disorder characterized by recurrent attacks of pain. Human and experimental models of migraine studies have demonstrated the role played by COX-2/ iNOS in migraine's neuroinflammatory pathogenesis. COX-2 and iNOS are closely linked and both contribute to inflammation and neurogenic pain in the central nervous system. Omega- 3 fatty acids and curcumin, an active polyphenol of turmeric, have anti-inflammatory and neuroprotective effects through several mechanisms, including the suppression of COX-2 and iNOS gene expression, as well as their serum levels. The aim of the present study is to evaluate the nutrigenomic effects of ω-3 fatty acids, nano-curcumin, and a combination of the two, on neuroinflammation and clinical symptoms in migraine patients.

Methods: This study reports the results of a clinical trial over a 2-month period, involving 74 episodic migraine patients who received ω-3 fatty acids, nano-curcumin, a combination of them, or a placebo. At the start and end of the study, the expression of COX-2/iNOS (in peripheral mononuclear blood cells isolated from patients) and COX-2/iNOS serum levels were measured, using real-time PCR and ELISA respectively. The frequency, severity and duration of pain attacks were also recorded.

Results: The results of the present trial showed that ω-3 fatty acids and nano-curcumin can reinforce each other's effects in the downregulation of COX-2/iNOS mRNA, as well as reduce their serum levels. In addition, the combination of ω-3 and nano-curcumin significantly reduced the frequency, severity and duration of headaches (P<0.05).

Conclusion: These findings indicate that combination therapy of ω-3 fatty acids and nano-curcumin can be considered as a promising new approach in migraine prevention.

Keywords: COX-2; Migraine; curcumin; headache; iNOS; ω-3 fatty acids..

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Curcumin / administration & dosage*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Dietary Supplements
  • Double-Blind Method
  • Drug Therapy, Combination
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Migraine Disorders / drug therapy*
  • Migraine Disorders / genetics
  • Migraine Disorders / metabolism
  • Nanoparticles / administration & dosage
  • Neuroprotective Agents / administration & dosage*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Placebos
  • Signal Transduction / drug effects
  • Treatment Outcome
  • Young Adult


  • Fatty Acids, Omega-3
  • Neuroprotective Agents
  • Placebos
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Curcumin