Omega-3 DHA

Overview

Docosahexaenoic acid (DHA, 22:6 n-3) is a 22-carbon polyunsaturated fatty acid with six cis double bonds — the longest and most unsaturated of the common omega-3s. Humans can synthesize DHA from its shorter-chain precursor α-linolenic acid (ALA) only inefficiently (typically <5% conversion), which makes dietary intake the practical primary source. DHA is concentrated in the phospholipids of neuronal membranes (particularly phosphatidylethanolamine and phosphatidylserine at synapses) and photoreceptor outer segments, where its flexibility supports membrane fluidity, receptor function, and synaptic transmission. DHA is also the precursor to specialized pro-resolving mediators — including resolvins and neuroprotectins — that actively resolve neuroinflammation. Supplemental forms include fish oil (triglyceride or ethyl ester), krill oil (phospholipid-bound), and algal DHA (a vegan, contaminant-free option manufactured from marine microalgae).

Mechanism of Action

DHA is incorporated directly into the sn-2 position of neuronal phospholipids, where its flexible, highly unsaturated tail maintains membrane fluidity and supports the function of embedded proteins (G-protein–coupled receptors, ion channels, neurotransmitter transporters). This structural role explains why DHA deficiency impairs synaptic transmission and long-term potentiation in preclinical models. Beyond structure, DHA serves as the substrate for enzymatic and non-enzymatic generation of specialized pro-resolving mediators (SPMs) — neuroprotectin D1 and the D-series resolvins — which resolve neuroinflammation and support neuronal survival. DHA also modulates gene expression via PPAR and retinoid X receptors, supports mitochondrial membrane integrity, and is the precursor to synaptamide (N-docosahexaenoylethanolamide), which promotes neurite growth, synaptogenesis, and neurogenesis through CB1/CB2-independent pathways.