The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are essential components of cellular membranes throughout the body, with particular importance in the cardiovascular system, brain, and retina. Unlike omega-6 fatty acids — which the modern Western diet delivers in excessive abundance — omega-3s must be obtained through diet or supplementation; the body cannot synthesize them in physiologically meaningful quantities from shorter-chain precursors.
The consequence of this dietary dependence is that omega-3 status is almost entirely a function of what people eat — and what most Americans eat contains very little EPA or DHA. National dietary survey data consistently show median long-chain omega-3 intake of approximately 100–170 mg per day, far below the 500 mg per day minimum associated with cardiovascular protection and the 1,000–2,000 mg range showing broader anti-inflammatory and neuroprotective benefits.
The Omega-6:Omega-3 Imbalance
The problem is not simply absolute omega-3 insufficiency but the profoundly distorted ratio of omega-6 to omega-3 fatty acids in the modern diet. Evolutionary estimates suggest our ancestors consumed omega-6s and omega-3s in a roughly 4:1 ratio. Contemporary Western diets commonly deliver this ratio at 15:1 to 20:1, driven by the ubiquitous presence of omega-6-rich refined vegetable oils (soybean, corn, sunflower) in processed foods.
This imbalance matters mechanistically. EPA and DHA compete with arachidonic acid — the primary omega-6-derived eicosanoid precursor — for the same enzymatic pathways that produce inflammatory signaling molecules. When EPA and DHA are scarce and arachidonic acid is abundant, the balance of eicosanoid production tilts toward pro-inflammatory species including prostaglandins E2, leukotriene B4, and thromboxane A2.
Cardiovascular Evidence: From Observational to Interventional
The cardiovascular benefits of omega-3 supplementation have been subject to two decades of debate, with earlier large trials producing inconsistent results and more recent high-dose EPA studies producing some of the most striking cardiovascular outcome data in recent memory.
The REDUCE-IT trial, published in 2019, randomized 8,179 patients with elevated triglycerides and established cardiovascular disease or diabetes to receive either 4 grams daily of icosapentaenoic acid ethyl ester (Vascepa) or mineral oil placebo. After a median 4.9-year follow-up, the EPA group showed a remarkable 25% relative risk reduction in major adverse cardiovascular events including cardiovascular death, nonfatal myocardial infarction, and stroke. The absolute risk reduction of 4.8 percentage points corresponded to a number needed to treat of 21 — exceptional by cardiovascular medicine standards.
Brain Health and Cognitive Aging
DHA constitutes approximately 40% of polyunsaturated fatty acids in the brain and is particularly concentrated in synaptic membranes, where it plays critical structural and functional roles in signal transduction, membrane fluidity, and neuroinflammatory regulation. Low plasma DHA has been consistently associated with accelerated cognitive aging and elevated risk of Alzheimer-type dementia in prospective cohort studies.
The neuroprotective mechanisms are multiple: DHA serves as a precursor to resolvins and protectins, bioactive lipid mediators that actively resolve neuroinflammation; it modulates BDNF expression, supporting neuronal survival and synaptic plasticity; and it regulates amyloid precursor protein processing, potentially influencing amyloid plaque accumulation.
Practical Guidance
For most adults seeking cardiovascular and general anti-inflammatory benefit, 1,000–2,000 mg per day of combined EPA+DHA from quality fish oil or algae-based omega-3 supplements represents a reasonable evidence-based target. Algal omega-3 is the preferred option for vegetarians and vegans — it provides DHA and increasingly EPA, bypasses fish entirely, and avoids concerns about marine contaminant accumulation.
Dietary sources remain important: two to three servings of fatty fish weekly (salmon, sardines, mackerel, anchovies) provide approximately 1,500–2,500 mg of EPA+DHA and confer benefits that likely extend beyond what omega-3 supplementation alone delivers, including contributions from selenium, vitamin D, astaxanthin, and marine protein.