Detection of omega-3 oxylipins in human plasma and response to treatment with omega-3 acid ethyl esters

The long-chain omega-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA) have beneficial health effects, but the molecular mediators of these effects are not well characterized. Oxygenated n-3 FAs (oxylipins) may be an important class of mediators. Members of this chemical class include epoxides, alcohols, diols, and ketones, many of which have bioactivity in vitro. Neither the presence of n-3 oxylipins in human plasma nor the effect of n-3 FA ingestion on their levels has been documented. We measured plasma oxylipins derived from both the n-3 and n-6 FA classes in healthy volunteers (n = 10) before and after 4 weeks of treatment with prescription n-3 FA ethyl esters (4 g/day). At baseline, EPA and DHA oxylipins were detected in low (1-50 nM) range, with alcohols > epoxides ≥ diols. Treatment increased n-3 oxylipin levels 2- to 5-fold and reduced selected n-6 oxylipins by ∼20%. This is the first documentation that endogenous n-3 oxylipin levels can be modulated by n-3 FA treatment in humans. The extent to which the beneficial cardiovascular effects of n-3 FAs are mediated by increased n-3 and/or reduced n-6 oxylipin levels remains to be explored.