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

Suzanne M Pilkington,Lesley E Rhodes,Anna Nicolaou,Karen A Massey,Naser M I Al‐Aasswad

doi:10.1002/mnfr.201300405

Abstract

ScopeEicosapentaenoic 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 resultsIn 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 PGE2, 12-hydroxyeicosatetraenoic acids, 12-HEPE (all p < 0.001) and PGE3 (p < 0.05). Post-EPA, PGE2 was reduced in unchallenged skin (p < 0.05) while EPA-derived PGE3 (non-sign) and 12-HEPE (p < 0.01) were elevated post-UVR. Thus, post-EPA, PGE2:PGE3 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).ConclusionDietary 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.

Highlights

Exposure of the skin to ultraviolet radiation (UVR) induces acute inflammation characterised clinically by erythema, which becomes visible after 4–6 h and peaks in intensity at 24–48 h post-exposure
The arachidonic acid (AA)-derived mediators PGE2 and 12-hydroxyeicosatetraenoic acids (HETE) are highly expressed, potent eicosanoids in basal and UVR-exposed skin [3]; they and their Eicosapentaenoic acid (EPA)-derived counterparts PGE3 and 12-HEPE were the focus of this assessment
The higher availability of EPA in the active group post-supplementation resulted in a doubling of the relative dermal EPA:AA content, which was accompanied by a doubling of the basal PGE3:PGE2 level, while following UVR-exposure, skin PGE3:PGE2 increased threefold and the 12-HEPE:12-HETE was fourfold higher than on control lipid (Fig. 3)

Summary

Introduction

Exposure of the skin to ultraviolet radiation (UVR) induces acute inflammation characterised clinically by erythema, which becomes visible after 4–6 h and peaks in intensity at 24–48 h post-exposure. This vasodilatory response is accompanied by a dermal leukocytic infiltrate comprising neutrophils, macrophage, mast cells and T-lymphocytes [1, 2] and, when severe, can be associated with oedema and pain. 12-HETE, the most abundant HETE expressed in UVR-inflamed skin, continues to rise at 72-h post-UVR exposure [3] This eicosanoid has powerful leukocyte chemoattractant properties [8,9,10] and is believed to promote the infiltration of leukocytes into the skin following UVR exposure [3]

Methods

Results

Conclusion