The synergistic effects of ω-3 fatty acids and nano-curcumin supplementation on tumor necrosis factor (TNF)-α gene expression and serum level in migraine patients

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