DHA

Docosahexaenoic acid (DHA, 22:6n-3) is a 22-carbon omega-3 polyunsaturated fatty acid with six cis double bonds, making it the most unsaturated fatty acid common in the human diet. DHA is the dominant omega-3 in neural tissue, retinal photoreceptors, and sperm, and is essential for normal brain development, visual function, and synaptic plasticity.

Tissue distribution

DHA is selectively incorporated into phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine of neural membranes. In retinal photoreceptor outer-segment disks, DHA comprises up to 40% of total fatty acids — an extraordinary enrichment that supports rhodopsin function and membrane fluidity required for visual signal transduction. In the cerebral cortex, DHA constitutes approximately 15-20% of phospholipid fatty acids; in sperm membranes, similarly high proportions support the fluidity required for fertilization.

Biosynthesis

Like EPA, DHA can be synthesized endogenously from alpha-linolenic acid, but with even lower efficiency than EPA — typically less than 0.5% of dietary ALA is converted to DHA in adult men, and somewhat higher (perhaps 2-9%) in women, reflecting estrogenic effects on desaturase activity. The conversion pathway involves elongation to 24:6n-3, a peroxisomal beta-oxidation step (the "Sprecher pathway"), yielding 22:6n-3 (DHA). Because endogenous synthesis is marginal, direct dietary DHA intake is considered functionally important for populations with elevated needs.

Dietary sources

Per USDA FoodData Central: salmon 0.5-0.9 g DHA per 100 g cooked, sardines 0.5-0.7 g, mackerel 0.6-1.2 g, herring 0.9 g, anchovies 0.5 g. Algal oil (from Schizochytrium and similar species) provides 100-500 mg DHA per capsule and serves as the principal vegetarian source. Human breast milk contains 0.1-0.4% of fatty acids as DHA, reflecting maternal dietary intake.

Neurodevelopment

The third trimester of pregnancy and the first two years of life are periods of rapid cerebral DHA accretion; adequate maternal intake and breast milk or formula DHA content support neurodevelopmental outcomes. FDA, WHO, and major pediatric bodies recommend at least 200 mg DHA/day during pregnancy and lactation. Infant formulas have been DHA-supplemented in most jurisdictions since the early 2000s, and omega-3 status in pregnancy is linked to visual acuity and language development outcomes in observational studies, with more mixed results in randomized trials of supplementation.

Cognitive aging

Observational studies associate higher omega-3 blood concentrations and fish intake with lower rates of cognitive decline and dementia. Randomized trials (OmegAD, MIDAS, LipiDiDiet) have produced mixed but generally modest results, with benefits most evident in subgroups with low baseline omega-3 status or specific genetic profiles (APOE genotype interactions). DHA is being actively investigated for prevention and early-stage intervention in Alzheimer's disease.

Specialized pro-resolving mediators

DHA is the substrate for D-series resolvins (RvD1-RvD6), protectins (PD1, neuroprotectin D1), and maresins — a suite of specialized pro-resolving mediators that actively resolve inflammation. Neuroprotectin D1 has been implicated in retinal and neural protection against oxidative stress.

Supplementation status

Fish oil supplements typically provide EPA:DHA in ratios of 1.5:1 to 2:1 (e.g., 1000 mg fish oil with 180 mg EPA + 120 mg DHA). Algal DHA supplements provide pure DHA. Krill oil provides phospholipid-bound EPA and DHA at lower total concentrations. Prescription omega-3 products (icosapent ethyl = pure EPA; omega-3-acid ethyl esters = EPA+DHA) are available at higher concentrations for hypertriglyceridemia management.