Omega-3 Fish Oil — Essential polyunsaturated fatty acid (n-3 PUFA)

EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) incorporate into phospholipid membranes and compete with arachidonic acid (AA) for cyclooxygenase and lipoxygenase enzymes, shifting eicosanoid production toward less pro-inflammatory resolvins and protectins. EPA reduces triglycerides via PPAR-α activation and VLDL secretion inhibition. DHA is critical for neuronal membrane fluidity and photoreceptor function. High-dose EPA reduces MACE (REDUCE-IT, n=8,179; STRENGTH). VITAL trial (n=25,871) showed 28% reduction in fatal MI.

Overview

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Compound Class

Essential polyunsaturated fatty acid (n-3 PUFA)

Mechanism of Action

EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) incorporate into phospholipid membranes and compete with arachidonic acid (AA) for cyclooxygenase and lipoxygenase enzymes, shifting eicosanoid production toward less pro-inflammatory resolvins and protectins. EPA reduces triglycerides via PPAR-α activation and VLDL secretion inhibition. DHA is critical for neuronal membrane fluidity and photoreceptor function. High-dose EPA reduces MACE (REDUCE-IT, n=8,179; STRENGTH). VITAL trial (n=25,871) showed 28% reduction in fatal MI.

Regulatory Status

OTC at standard doses. Prescription-grade high-purity forms (Vascepa/Icosapentaenoic acid, Lovaza) FDA-approved for severe hypertriglyceridemia and CV risk.

Evidence Level

High — multiple large RCTs. FDA-approved prescriptions at 4 g/day (Vascepa, Lovaza). AHA position statement supports use for hypertriglyceridemia and cardiovascular risk.