Randomized controlled trial of oral omega-3 PUFA in solar-simulated radiation-induced suppression of human cutaneous immune responses

Pilkington, Suzanne M.; Massey, Karen A.; Bennett, Susan; Al-Aasswad, Naser M. I.; Roshdy, K; Gibbs, Neil K.; Friedmann, Peter S.; Nicolaou, Anna; Rhodes, Lesley E.

doi:10.3945/ajcn.112.049494

Cited by 40 publications

(49 citation statements)

References 58 publications

(73 reference statements)

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“…To date there has been no comprehensive review of existing epidemiological data regarding the relationship between dietary n‐3 PUFAs and the incidence of skin cancer, although a number of potentially relevant biological mechanisms have been proposed . In vitro , n‐3 PUFAs not only protect against UV‐induced damage but promote appropriate immunological responses and hairless mice given diets rich in n‐3 PUFAs show significant reductions in cutaneous malignancy through promotion of tumor latency and inhibition of tumor multiplicity .…”

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confidence: 99%

Consumption of omega‐3 fatty acids and the risk of skin cancers: A systematic review and meta‐analysis

Noël¹,

Stoneham

Olsen

et al. 2013

Intl Journal of Cancer

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Skin cancers have a higher incidence than all other cancers combined and are a major cause of morbidity worldwide. Laboratory data suggest certain dietary constituents, notably omega-3 polyunsaturated fatty acids (n-3 PUFAs), could potentially protect against skin malignancy, although no large-scale review has been conducted in humans. The objective of this review and meta-analysis was to determine the relationship between dietary n-3 PUFAs and skin cancer incidence. It considered all published randomized controlled trials and observational studies up to March 2013. Five studies (two case-control and three cohort) were identified pertaining to oral n-3 PUFA consumption and incidence of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma (or a combination) and were included in a random-effects meta-analysis. A further six studies considering nondietary n-3 PUFA exposure (e.g. by tissue analysis) and/or recognized biological markers of skin cancer risk (e.g. p53 expression) were analyzed qualitatively. Dietary n-3 PUFAs were not associated with BCC (pooled OR 1.05, 95% CIs 0.86-1.28). Consumption of high levels of n-3 PUFAs were inversely associated with melanoma, although with only one estimate available (OR 0.52, 95% CI 0.34-0.78), and SCC, although nonsignificantly (pooled OR 0.86, 95% CIs 0.59-1.23). Available evidence is suggestive, but currently inadequate, to support the hypothesis that n-3 PUFAs protect against skin malignancy.

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confidence: 99%

Consumption of omega‐3 fatty acids and the risk of skin cancers: A systematic review and meta‐analysis

Noël¹,

Stoneham

Olsen

et al. 2013

Intl Journal of Cancer

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“…[14][15][16][17] Recent studies evidence the extensive cutaneous profile of lipid mediators in human skin, encompassing the endocannabinoids, NAE, sphingolipids and eicosanoid families. [17][18][19][20][21] Some of these lipid species are known to be modulated by UVR and to play a role in photobiological effects in humans 22,23 whilst the potential involvement of the endocannabinoids and their congeners in UVRinduced effects, awaits further exploration. The main endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), and a range of N-acyl ethanolamine (NAE) species, derive from membrane lipids (Fig.…”

Section: Introductionmentioning

confidence: 99%

Serum endocannabinoids and N-acyl ethanolamines and the influence of simulated solar UVR exposure in humans in vivo

Felton

Kendall

Almaedani

et al. 2017

Photochem Photobiol Sci

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Solar ultraviolet radiation (UVR) exposure of human skin has beneficial and harmful effects on health, including impact on immune function, inflammation and reportedly mood, but these are not fully elucidated. Since the endocannabinoid system is implicated in many activities including mood alteration, our objective was to (i) determine and quantify circulating levels of a wide range of endocannabinoid and N-acyl ethanolamine (NAE) species (ii) evaluate whether these are modulated by cutaneous UVR exposures, as attained through repeated low level summer sunlight exposure. Wearing goggles to prevent eye exposure, 16 healthy volunteers (23-59y; 10 light skin, phototype II, and 6 dark skin, phototype V) received the same UVR exposures (1.3 SED, 95%UVA/5% UVB) thrice weekly for 6 weeks, whilst casually dressed to expose ~35% skin surface area. Blood samples were taken at baseline, days 1, 3 and 5 of week one, then at weekly intervals, and analysed by LC-MS/MS. Eleven endocannabinoids and NAEs were detected and quantified at baseline, with Npalmitoyl ethanolamine the most abundant (30% of total). Levels did not vary according to phototype (p>0.05), except for the NAE docosapentaenoyl ethanolamide, which was higher in phototype II than V (p=0.0002). Level of the endocannabinoid, 2-AG, was elevated during the UVR exposure course (p<0.05 vs baseline for all subjects; p<0.01 for each phototype group), with maximum levels reached by week 2-3, while NAE species did not significantly alter. These findings suggest differential involvement of the cutaneous endocannabinoid system in low dose solar UVR responses in humans.3

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“…The Omega‐3 polyunsaturated fatty acid (n‐3 PUFA) eicosapentaenoic acid (EPA) reduces UVR suppression of CMI in vivo; in mice, both topical and systemic EPA‐rich lipids reduced UVR suppression of chemically induced CHS responses by up to 90% . Further, we recently observed in a randomised controlled trial (RCT) in humans that oral EPA supplementation showed potential to reduce UVR suppression of nickel CHS . While the mean group difference for the three solar‐simulated radiation (SSR) doses we employed showed no statistically significant protection by EPA, ~50% reduction of photoimmunosuppression was noted with UVR dosing equivalent to brief exposure to summer sunlight (post hoc analysis P <.05) .…”

Section: Introductionmentioning

confidence: 88%

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

Pilkington

Gibbs

Costello

et al. 2016

Experimental Dermatology

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28Langerhans cells (LC) are sentinels of skin's immune system, their loss from epidermis 29 contributing to UVR-suppression of cell mediated immunity (CMI). Omega-3 polyunsaturated 30 fatty acids can show potential to abrogate UVR-suppression of CMI in mice and humans, 31 potentially through modulation of LC migration. Our objectives were to examine if 32 eicosapentaenoic acid (EPA) ingestion influences UV-mediated effects on epidermal LC 33 numbers and levels of immunomodulatory mediators including prostaglandin (PG)D 2 , which 34 is expressed by LC. 35In a double-blind randomised controlled study, healthy individuals took 5g EPA-rich 36 (n=40) or control (n=33) lipid for 12-weeks; UVR exposed and unexposed skin samples were 37 taken pre-and post-supplementation. Epidermal LC numbers were assessed by 38 immunofluorescence for CD1a, and skin blister fluid PG and cytokines quantified by LC-39 MS/MS and Luminex assay, respectively. Pre-supplementation, UVR reduced mean (SEM) 40LC number/mm 2 from 913 (28) to 322 (40) (p<0.001), and mean PGD 2 level by 37% from 8.1 41 (11.6) to 5.1 (5.6) pg/µl; p<0.001), while IL-8 level increased (p<0.001). Despite confirmation 42 of EPA bioavailability in red blood cells and skin in the active group, no between-group effect 43 of EPA was found on UVR-modulation of LC numbers, PGD 2 or cytokine levels post-44 supplementation. 45

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Randomized controlled trial of oral omega-3 PUFA in solar-simulated radiation-induced suppression of human cutaneous immune responses

Abstract: Oral n-3 PUFAs appear to abrogate photoimmunosuppression in human skin, providing additional support for their chemopreventive role; verification of study findings is required. This trial was registered at clinicaltrials.gov as NCT01032343.

Cited by 40 publications

References 58 publications

Consumption of omega‐3 fatty acids and the risk of skin cancers: A systematic review and meta‐analysis

Consumption of omega‐3 fatty acids and the risk of skin cancers: A systematic review and meta‐analysis

Serum endocannabinoids and N-acyl ethanolamines and the influence of simulated solar UVR exposure in humans in vivo

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

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Randomized controlled trial of oral omega-3 PUFA in solar-simulated radiation-induced suppression of human cutaneous immune responses

Abstract: Oral n-3 PUFAs appear to abrogate photoimmunosuppression in human skin, providing additional support for their chemopreventive role; verification of study findings is required. This trial was registered at clinicaltrials.gov as NCT01032343.

Cited by 40 publications

References 58 publications

Consumption of omega‐3 fatty acids and the risk of skin cancers: A systematic review and meta‐analysis

Consumption of omega‐3 fatty acids and the risk of skin cancers: A systematic review and meta‐analysis

Serum endocannabinoids and N-acyl ethanolamines and the influence of simulated solar UVR exposure in humans in vivo

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

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