Migraine is a destabilizing
neuroinflammatory disorder characterized by recurrent
headache attacks. Evidences show
tumor necrosis factor (TNF)-α play a role in neuroimmunity pathogenesis of
migraine. TNF-α increase
prostanoid production, hyperexcitability of neurons, and nociceptor activation resulted in
neuroinflammation and neurogenic
pain. ω-3
fatty acids and
curcumin exert neuroprotective and anti-inflammatory effects via several mechanisms including suppression of TNF-α gene expression and its serum levels. The aim of this study is an evaluation of synergistic effects of ω-3
fatty acids and nano-
curcumin on TNF-α gene expression and serum levels in
migraine patients. The present study performed as a clinical trial over a 2 month period included 74 episodic
migraine patients in 4 groups and received ω-3
fatty acids, nano-
curcumin, and combination of them or placebo. At the start and the end of the study, the gene expression of TNF-α and TNF-α serum levels was measured by real-time PCR and ELISA method, respectively. Our results showed that the combination of ω-3
fatty acids and nano-
curcumin downregulated TNF-α
messenger RNA (
mRNA) significantly in a synergistic manner (P < 0.05). As relative to gene expression, a significant greater reduction in serum levels of TNF-α were observed in the combination group, but no significant differences in other groups. Supplementation with ω-3
fatty acids or nano-
curcumin alone did not show significant reduction either in
mRNA or serum levels of TNF-α. In addition, a much greater reduction in attack frequency was found in the combination group (P < 0.001). These findings indicated that ω-3
fatty acids and
curcumin supplementation can be considered as a new promising approach in
migraine management.