Impact of EPA ingestion on COX ‐ and LOX ‐mediated eicosanoid synthesis in skin with and without a pro‐inflammatory UVR challenge – Report of a randomised controlled study in humans

Scope Eicosapentaenoic acid ( EPA ), abundant in oily fish, is reported to reduce skin inflammation and provide photoprotection, potential mechanisms include competition with arachidonic acid ( AA ) for metabolism by cyclooxygenases/lipoxygenases to less pro‐inflammatory mediators. We thus examine impact of EPA intake on levels of AA , EPA and their resulting eicosanoids in human skin with or without ultraviolet radiation ( UVR ) challenge. Methods and results In a double‐blind randomised controlled study, 79 females took 5 g EPA ‐rich or control lipid for 12 wk. Pre‐ and post‐supplementation, red blood cell and skin polyunsaturated fatty acids were assessed by GC , and eicosanoids from unexposed and UVR ‐exposed skin by LC ‐ MS / MS . Active supplementation increased red blood cell and dermal EPA versus control (both p < 0.001), lowering relative AA : EPA content (4:1 versus 15:1 and 5:1 versus 11:1, respectively; both p < 0.001). Pre‐supplementation, UVR increased PGE 2 , 12‐hydroxyeicosatetraenoic acids, 12‐ HEPE (all p < 0.001) and PGE 3 ( p < 0.05). Post‐ EPA , PGE 2 was reduced in unchallenged skin ( p < 0.05) while EPA ‐derived PGE 3 (non‐sign) and 12‐ HEPE ( p < 0.01) were elevated post‐ UVR . Thus, post‐ EPA , PGE 2 : PGE 3 was lower in unchallenged (12:1 versus 28:1; p < 0.05) and UVR exposed (12:1 versus 54:1; p < 0.01) skin; 12‐hydroxyeicosatetraenoic acids:12‐ HEPE was lower in UVR ‐exposed skin (3:1 versus 11:1; p < 0.001). Conclusion Dietary EPA augments skin EPA : AA content, shifting eicosanoid synthesis towards less pro‐inflammatory species, and promoting a regulatory milieu under basal conditions and in response to inflammatory insult.