Fish oil is an oil extracted from the tissue of fatty fish, rich in two omega-3 fatty acids that your body can’t efficiently make on its own: EPA and DHA. These two fats play structural roles in cell membranes throughout your body and are especially concentrated in the brain, where DHA alone accounts for over 90% of all omega-3 fats and 10% to 20% of the brain’s total fat content. Fish oil is consumed both through whole fish and as a concentrated supplement, making it one of the most widely used dietary supplements worldwide.
What’s Actually in Fish Oil
The two active ingredients that matter are EPA and DHA. Both are long-chain omega-3 fatty acids, meaning they have a specific molecular shape that your body uses differently from the shorter omega-3 (ALA) found in plant foods like flaxseed and walnuts. EPA has 20 carbon atoms and DHA has 22, compared to ALA’s 18. That extra length is what allows them to integrate into cell membranes and influence how cells communicate.
Your body can technically convert ALA into EPA and DHA, but the conversion rate is extremely low, which is why dietary sources of the longer-chain forms matter. A standard fish oil supplement capsule contains varying concentages of EPA and DHA, with the rest made up of other fats, and the ratio between the two differs by product. Some formulations emphasize EPA, others DHA, and many provide a roughly even split.
How Fish Oil Works in the Body
When you consume EPA and DHA, they gradually replace other fats in the membranes of your cells, including immune cells. This swap changes how those cells behave. Normally, cell membranes contain a high proportion of a fat called arachidonic acid, which the body uses as raw material to produce inflammatory signaling molecules. As EPA and DHA accumulate in those membranes, they crowd out arachidonic acid and reduce the supply of pro-inflammatory building blocks.
The anti-inflammatory effect goes beyond just displacing one fat with another. EPA and DHA also change the physical structure of cell membranes in ways that disrupt the signaling platforms immune cells use to ramp up inflammation. They dial down the activity of a key molecular switch that turns on inflammatory genes, while simultaneously activating a separate switch that suppresses inflammation. DHA in particular binds to a receptor on immune cells called GPR120. When researchers blocked this receptor in lab studies, DHA lost its ability to calm the immune response, confirming that this receptor is a major pathway for the anti-inflammatory effect.
The result is lower production of inflammatory signaling molecules like TNF-alpha and IL-6, both of which drive chronic, low-grade inflammation linked to heart disease, joint pain, and metabolic problems.
Effects on Heart Health
The most studied benefit of fish oil is its ability to lower triglycerides, a type of fat in the blood that raises cardiovascular risk when elevated. At high doses (around 4 grams per day of combined EPA and DHA), fish oil reduces triglycerides by 20% to 30% or more, depending on how high levels are to start with. In people with very high triglycerides (500 mg/dL or above), reductions of 30% or greater have been documented in clinical trials.
There’s an important nuance here. Supplements that combine EPA and DHA can raise LDL cholesterol by roughly 15% to 36% in people with very high triglycerides. EPA-only formulations do not appear to cause this increase. In the REDUCE-IT trial, an EPA-only prescription product taken alongside a statin lowered triglycerides by about 20% while also reducing LDL cholesterol by 7% and other markers of cardiovascular risk.
DHA and the Brain
DHA is the dominant structural fat in brain tissue, concentrated heavily in gray matter and enriched at synaptic terminals, the junctions where nerve cells communicate. It influences membrane fluidity, neurotransmitter release, and the formation of new nerve cells. Total synaptic loss is the strongest predictor of cognitive decline during aging, and DHA has demonstrated effects on both the strength and number of synapses.
In the context of age-related cognitive decline, DHA appears to work through several pathways. It helps counteract oxidative stress and neuroinflammation, two processes that accelerate brain aging. It can reduce levels of a damaged form of tau protein, one of the hallmarks of Alzheimer’s disease, by inhibiting the enzymes that cause tau to become dysfunctional. DHA also appears to slow the formation of amyloid plaques and can stimulate immune cells in the brain to clear amyloid fragments. Brain glucose metabolism drops 10% to 15% during normal aging and can fall by nearly 35% in certain brain regions during Alzheimer’s, so maintaining the structural integrity of brain cell membranes with adequate DHA may help preserve normal energy use.
Best Dietary Sources
Fatty, cold-water fish provide the highest concentrations of EPA and DHA per serving. The amount varies significantly by species. Per 3.5-ounce (100-gram) serving:
- Lake trout: roughly 1,650 mg combined EPA and DHA
- Farmed salmon: roughly 1,120 mg
- Lake herring: roughly 600 mg
- Whitefish: roughly 590 mg
- Rainbow smelt: roughly 500 mg
- Canned tuna: roughly 550 mg
- Wild cod: roughly 300 mg
- Walleye: roughly 220 mg
- Tilapia: roughly 47 mg
The gap between species is dramatic. A single serving of lake trout delivers more than 35 times the omega-3s found in the same amount of tilapia. If you’re eating fish specifically for omega-3 content, the type of fish matters far more than simply eating “more fish.”
Supplement Forms and Absorption
Fish oil supplements come in several chemical forms, and the form affects how well your body absorbs them. Natural fish oil contains EPA and DHA attached to a glycerol backbone as triglycerides. During processing, many manufacturers convert these to ethyl esters, a synthetic form that’s easier to concentrate and purify. Some products then convert the ethyl esters back into triglyceride form, called re-esterified triglycerides.
The absorption differences are significant. Compared to natural fish oil as the baseline, re-esterified triglycerides showed 124% bioavailability, meaning slightly better absorption. Ethyl esters, on the other hand, showed only 73% bioavailability, about a quarter less than natural fish oil. In practical terms, if you’re taking an ethyl ester product, you’re absorbing roughly 40% less EPA and DHA than you would from a re-esterified triglyceride product at the same dose.
How Fish Oil Is Purified
Because fish can accumulate mercury, PCBs, and dioxins, commercial fish oil goes through extensive refining. The process starts with degumming using phosphoric acid, followed by neutralization and centrifugation to remove free fatty acids. Bleaching with activated carbon or clay removes pigments, trace metals, and environmental contaminants. Carbon-based adsorbents can remove up to 99% of dioxins and about 70% of hexachlorobenzene. Finally, steam distillation under vacuum strips out odor compounds and remaining impurities without damaging the heat-sensitive omega-3 fats.
Higher-end products use molecular distillation, which operates at high vacuum levels to physically separate fatty acids by their boiling points. This allows manufacturers to concentrate EPA and DHA while removing shorter-chain and saturated fats, producing a more potent final product.
Side Effects and Blood Thinning Concerns
Common side effects of fish oil supplements include fishy aftertaste, digestive discomfort, and loose stools, particularly at higher doses. Taking capsules with meals and storing them in the freezer can reduce the aftertaste.
A persistent concern is that fish oil might dangerously thin the blood, especially in people taking anticoagulant medications. The clinical evidence, however, does not support this. A retrospective study of patients on warfarin found that fish and krill oil did not significantly alter the time patients spent in their therapeutic anticoagulation range, nor did it increase bleeding incidence. A randomized trial giving warfarin patients 3 to 6 grams of fish oil daily for four weeks found no significant effect on anticoagulation control. In a larger trial of 610 patients taking either aspirin or warfarin, those randomized to 4 grams of omega-3 fatty acids for nine months showed no excess bleeding events compared to placebo. While a handful of individual case reports have described elevated bleeding markers, the overall body of human evidence does not support a clinically meaningful interaction between fish oil and blood thinners at typical supplemental doses.