Mammals lack the desaturases to make omega-3 (ω3) and omega-6 (ω6) fatty acids de novo — they must come from diet. ALA (α-linolenic, ω3) → EPA → DHA via FADS2 (Δ6-desaturase) + elongases + FADS1 (Δ5). Conversion rate ALA → EPA → DHA is low (<10%) — explains why dietary EPA/DHA from fish oil has effects ALA supplementation doesn't reproduce. Linoleic (ω6) → arachidonic acid (AA) via the same enzyme set — competes with ω3 desaturation. SPMs (specialized pro-resolving mediators): from EPA → E-series resolvins; from DHA → D-series resolvins + protectins + maresins. SPMs actively terminate inflammation (vs glucocorticoids which suppress it) — therapeutic interest is growing.
Organ Systems
cardiovascular
immune-hematologic
nervous
Pathway Steps
alpha-linolenic-acid → eicosapentaenoic-acid — via FADS2 + elongases + FADS1; conversion <10% in most humans. Endogenous conversion of plant ALA to EPA is inefficient (<10%, often <5%, lower in men) — the basis for recommending preformed marine EPA. EPA also competes with arachidonic acid for the eicosanoid enzymes, shifting toward less-inflammatory mediators.
eicosapentaenoic-acid → docosahexaenoic-acid — via elongases + FADS2 + retroconversion. EPA→DHA conversion is likewise limited (and partly retroconverts), so DHA — uniquely concentrated in brain and retinal membranes — is best obtained preformed. Algal oil is a vegan DHA source that bypasses the poor conversion.
eicosapentaenoic-acid → resolvin-e1 — via aspirin-triggered + cox-2 + ALOX5 → E-series resolvins. EPA is the substrate for E-series resolvins — specialized pro-resolving mediators that actively terminate inflammation rather than merely block it. Aspirin-acetylated COX-2 makes the aspirin-triggered forms, a proposed contributor to aspirin’s benefits.
docosahexaenoic-acid → resolvin-d1 — via ALOX15 + ALOX5 → D-series resolvins + protectins + maresins. DHA yields D-series resolvins, protectins, and maresins — the specialized pro-resolving mediator (SPM) family that drives active resolution of inflammation and tissue repair, reframing omega-3 benefit as pro-resolution, not simple anti-inflammation.
Known Modulators
epa dha (substrate) — EPA + DHA pool replenishment from dietary fish oil
aspirin (activator) — cox-2 acetylation produces aspirin-triggered resolvins from EPA
ala (substrate) — omega-3 ALA → EPA/DHA (low conversion). α-linolenic acid; plant omega-3; <5% converts to EPA/DHA in humans