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

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.

Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD2 production in UVR‐exposed human skin: a randomised controlled study

“…Baseline dietary intake assessed by food frequency questionnaire was below current UK recommendations of 450 mg/d total long chain n‐3 PUFA . The EPA supplement was bioavailable in both RBC and skin ( P <.001) as previously reported . Three volunteers in the EPA group (all suction blister subgroup) who showed no increase in RBC EPA levels postsupplementation were excluded from analyses for poor compliance (Fig.…”

“…After 24 hours, skin suction blistering and skin punch biopsy were performed from UVR‐exposed and unexposed sites (methods as described in ref. ). The 4× MED dose was chosen to provide a sufficient challenge to produce quantifiable increases in cytokine and eicosanoid expression in human skin in vivo …”

Decreased hepatic phosphorylated p38 mitogen-activated protein kinase contributes to attenuation of thioacetamide-induced hepatic necrosis in diet-induced obese mice

“…Compared to the vehicletreated HFD mice, at 24 hr after TA administration, only one pro-inflammatory mediator, 12-HETE (Cunningham et al, 1985), was higher in the HFD mice. On the other hand, in addition to 12-HETE, 2 pro-inflammation-related metabolites, 15-HETE (Calder, 2009) and 12-HEPE (Pilkington et al, 2014;Strassburg et al, 2012), were higher in the ND mice in comparison to the vehicle-treated ND mice. Moreover, the omega-3 polyunsaturated fatty acid eicosapentaenoate and the omega-6 polyunsaturated fatty acids, linoleate and arachidonate (Chen et al, 1996), were significantly lower and the ratio of omega-3/ omega-6 polyunsaturated fatty acids was apparently lower only in the ND mice at 24 hr.…”

“…3A and 3B). Table 1 shows the results of the metabolomics analysis on unsaturated fatty acids and their metabolites, which have been reported to relate to pro-inflammation state (Tam, 2013;Cunningham et al, 1985;Calder, 2009;Pilkington et al, 2014;Strassburg et al, 2012;Elabdeen et al, 2013;Kalogeropoulos et al, 2010). These mediators were measured at 8 and 24 hr after TA administration.…”

Nutraceuticals and skin appearance: Is there any evidence to support this growing trend?

“…To examine whether EPA has anti‐inflammatory effects in skin, in a double‐blind RCT an EPA‐rich supplement (~3.5 g EPA and 0.5 g DHA) or 5 g of control oil (MCTs) was given to 79 women with nickel contact allergy every day for 12 weeks (Pilkington et al . ). Skin on the buttock was exposed to four times the individual's MED of UV radiation.…”