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Migraine is a chronic inflammatory neurological disease which has progressive and episodic course. Poly unsaturated fatty acids are an important component of cell membrane phospholipids. The intake of this, specially omega 3 fatty acid rich foods related to decrease concentration of CRP, proinflammatory cytokines, eicosaniods and chemokines.


Migraine is a common chronic disease with nerve inflammation and dysfunction of the vascular endothelial cell. (1)The prevalence of a migraine is 17% in women and 7-8% in men. (2-4) Although the cause of migraine is still unknown, many factors involved in its pathogenesis include genetic factors, cerebral vasoconstriction, increased levels of glutamate in the attack phase, magnesium deficiency, monoaminergic pathway disorders, mitochondrial disorders, calcitonin gene-related peptide (CGRP) and neurogenic inflammation. (5) A large number of studies proved anti inflammatory and neuroprotective effects of omega 3 fatty acids.(6-7)

Neuro-inflammation: Only after disruption of blood brain barrier inflammatory mediators spread throughout brain tissue and cause wide spread inflammation. Immune cells produce active complement, cytokine, chemokines, IL, nitric oxide (NO), reactive oxygen species (ROS) and growth factors. These releasing substances have devastating effects on cells and cause of more damage.(8)

Anti- inflammatory and neuro protective role of omega 3 fatty acids:

DHA and EPA, PUFA which are part of omega 3 fatty acids. DHA and EPA, through the cyclooxygenase and lipoxygenase enzymatic pathway, cause production of Resolvins and related compounds with anti-inflammatory effects such as Protectine. Resolvin E1 (RvE1), Resolvin D1 (RvD1) and Protectin D1 evoke inhibition of migration of neutrophils from endothelial membrane. Some of the effects of omega-3 PUFA are related to modulation of the amount and types of eicosanoids which are made from omega-3 fatty acids.(10)

Another mechanism of PUFA is through PPAR-ϒ. The PPAR-Υ is a transcription factor that has anti-inflammatory function and can directly regulate the expression of inflammatory genes. It interferes with the activation of NFkB responsible for reducing the response of macrophages, decreasing phosphorylation  of  IkB (more NFkB activity) and production of TNF-α and IL-6.(11) Therefore, omega-3 fatty acids are remarkably effective in the treatment of inflammation and can be considered in the treatment of inflammatory pain.(9)

In rats, they studied PUFA significantly reduces oxidative stress and NO production in microglia and also having neuroprotective action.(11) The effects of sodium valproate and fish oil when both are given to patients with migraine, in combination or alone, the results showed that the significant reduction of duration, frequency, and severity of a headache has been observed in the group receiving the synergistic effect of fish oil and sodium valproate, as compared to the group receiving medication alone. Therefore, receiving sodium valproate with fish oil can control the severity of migraine disease more effectively than receiving sodium valproate alone.(12)

It has been shown that 2 months supplementation with 1 g of omega-3 fatty acids significantly decreased the frequency of headaches and also patients reported 74% reduction in the duration of their headache.(13)


Omega 3 fatty acids, especially EPA, an alternative diatery supplementation therapy can be potentially important for neuroinflammatory as well autoimmune disorders.


  1. Robbins MS, Ailani J. Epidemiology, progression, prognosis, and comorbidity of trigeminal autonomic cephalalgias. In: Robbins M, Grosberg BM, Lipton R, Editors. Headache. New York, NY: John Wiley & Sons; 2013. p. 192-200.
  2. Hamed SA. The vascular risk associations with migraine: Relation to migraine          susceptibility and progression. Atherosclerosis 2009; 205(1): 15-22.
  3. Burch RC, Loder S, Loder E, Smitherman TA. The prevalence and burden of migraine and severe headache in the United States: Updated statistics from government health surveillance studies. Headache 2015; 55(1): 21-34.
  4. Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: Data from the American Migraine Study II. Headache 2001; 41(7): 646-57.
  5. Goua M, Mulgrew S, Frank J, Rees D, Sneddon AA, Wahle KW. Regulation of adhesion molecule expression in human endothelial and smooth muscle cells by omega-3 fatty acids and conjugated linoleic acids: Involvement of the transcription factor NF-kappaB? Prostaglandins Leukot Essent Fatty Acids 2008; 78(1): 33-43.
  6. De Caterina R, Madonna R, Massaro M. Effects of omega-3 fatty acids on cytokines and adhesion molecules. Curr Atheroscler Rep 2004; 6(6): 485-91.
  7. Sedighiyan M, Abdolahi M, Mohammadzadeh Honarvar N, Hosseini B, Djafarian K. Curcumin a novel agent targeting inflammatory pathways in obesity. Journal of Nutritional Sciences And Dietetics 2016; 2(5)
  8. Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 2002; 21(6): 495-505.
  9. Xu ZZ, Zhang L, Liu T, Park JY, Berta T, Yang R, et al. Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions. Nat Med 2010; 16(5): 592-7, 1p.
  10. Bazan NG, Molina MF, Gordon WC. Docosahexaenoic acid signalolipidomics in nutrition: Significance in aging, neuroinflammation, macular degeneration, Alzheimer's, and other neurodegenerative diseases. Annu Rev Nutr 2011; 31: 321-51.
  11.  Corsi L, Dongmo BM, Avallone R. Supplementation of omega 3 fatty acids improves oxidative stress in activated BV2 microglial cell line. Int J Food Sci Nutr 2015; 66(3): 293-9.
  12. Tajmirriahi M, Sohelipour M, Basiri K, Shaygannejad V, Ghorbani A, Saadatnia M. The effects of sodium valproate with fish oil supplementation or alone in migraine prevention: A randomized single-blind clinical trial. Iran J Neurol 2012; 11(1): 21-4.
  13. Harel Z, Gascon G, Riggs S, Vaz R, Brown W, Exil G. Supplementation with omega-3 polyunsaturated fatty acids in the management of recurrent migraines in adolescents. J Adolesc Health 2002; 31(2): 154-61.

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