ReviewOmega-3 fatty acids and cytochrome P450-derived eicosanoids in cardiovascular diseases: Which actions and interactions modulate hemodynamics?

- Observational studies and RCTs suggest that omega-3 FA can be cardioprotective.
- Omega-3 compete with omega-6 for the metabolism via CYP450.
- Omega-3 metabolites via CYP450 might have a higher vasodilatatory capacity.
- These hemodynamic effects by omega-3 could mediate their vascular beneficial effect.
- Interactions with other nutrients can interfere with beneficial omega-3 actions.

Increasing interest is focused on omega-3 fatty acids (FA) because of their potential beneficial effects, particularly in cardiovascular disease prevention. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), two major omega-3 FA, are mainly consumed through diet, particularly from fish and seafood intake, whereas alpha-linolenic acid (ALA) is present in high amounts in leafy green vegetables, nuts and seeds. The hypothesis of a cardiovascular protective action of omega-3 FA derives mainly from observational studies, whereas the evidence from interventional studies is not always consistent. Nonetheless, clinical trials and meta-analyses indicate a positive action, at minimum on blood pressure (BP). Omega-3 FA may act through different biological pathways; however, in our review, we seek to revisit, most notably, the role of their metabolites via cytochrome P450 (CYP450) in hemodynamic modulation. We emphasize that the effect of omega-3 FA may depend on their balance with other dietary compounds, particularly omega-6 FA, which compete for the same pathways, thus modulating the production of metabolites. Furthermore, the biological activity of omega-3 FA might be better explained by the complex balance and interactions between a variety of nutrients and polymorphisms of genes implicated in specific metabolic pathways.