Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers

Carcinogenesis. 2003 May;24(5):919-25. doi: 10.1093/carcin/bgg038.


Dietary omega-3 polyunsaturated fatty acids (omega-3 PUFAs) protect against photocarcinogenesis in animals, but prospective human studies are scarce. The mechanism(s) underlying the photoprotection are uncertain, although omega-3 PUFAs may influence oxidative stress. We examined the effect of supplementation on a range of indicators of ultraviolet radiation (UVR)-induced DNA damage in humans, and assessed effect on basal and post-UVR oxidative status. In a double-blind randomized study, 42 healthy subjects took 4 g daily of purified omega-3 PUFA, eicosapentaenoic acid (EPA), or monounsaturated, oleic acid (OA), for 3 months. EPA was bioavailable; the skin content at 3 months showing an 8-fold rise from baseline, P < 0.01. No consistent pattern of alteration in basal and UVR-exposed skin content of the antioxidants glutathione, vitamins E and C or lipid peroxidation, was seen on supplementation. Sunburn sensitivity was reduced on EPA, the UVR-induced erythemal threshold rising from a mean of 36 (SD 10) mJ/cm(2) at baseline to 49 (16) mJ/cm(2) after supplementation, P < 0.01. Moreover, UVR-induced skin p53 expression, assessed immunohistochemically at 24 h post-UVR exposure, fell from a mean of 16 (SD 5) positive cells/100 epidermal cells at baseline to 8 (4) after EPA supplementation, P < 0.01. Peripheral blood lymphocytes (PBL) sampled on 3 successive days both pre- and post-supplementation, showed no change with respect to basal DNA single-strand breaks or oxidative base modification (8-oxo-dG). However, when susceptibility of PBL to ex vivo UVR was examined using the comet assay, this revealed a reduction in tail moment from 84.4 (SD 3.4) at baseline to 69.4 (3.1) after EPA, P = 0.03. No significant changes were seen in any of the above parameters following OA supplementation. Reduction in this range of early markers, i.e. sunburn, UVR-induced p53 in skin and strand breaks in PBL, indicate protection by dietary EPA against acute UVR-induced genotoxicity; longer-term supplementation might reduce skin cancer in humans.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Ascorbic Acid / metabolism
  • Biological Availability
  • DNA / radiation effects
  • DNA Damage
  • DNA Repair
  • Dietary Supplements
  • Double-Blind Method
  • Eicosapentaenoic Acid / pharmacokinetics
  • Eicosapentaenoic Acid / pharmacology*
  • Female
  • Genetic Markers
  • Glutathione / metabolism
  • Humans
  • Lipid Peroxidation
  • Lymphocytes / radiation effects
  • Male
  • Middle Aged
  • Neoplasms, Radiation-Induced / genetics
  • Neoplasms, Radiation-Induced / prevention & control*
  • Oleic Acid / pharmacokinetics
  • Oleic Acid / pharmacology
  • Skin / metabolism
  • Skin / radiation effects*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / prevention & control*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Ultraviolet Rays
  • Vitamin E / metabolism


  • Genetic Markers
  • Tumor Suppressor Protein p53
  • Vitamin E
  • Oleic Acid
  • DNA
  • Eicosapentaenoic Acid
  • Glutathione
  • Ascorbic Acid