As you likely know (and as I’ve been discussing for years), omega-3 fatty acids have anti-inflammatory properties. They have been studied for the treatment and prevention of many diseases, several of which are related to inflammation, including heart disease, stroke, cancer, and Alzheimer’s disease. They have also been shown to be extraordinarily helpful in preventing and treating other brain conditions such as depression and other psychiatric disorders, attention deficit/hyperactivity disorder (ADHD), and concussions.
If, however, we want to target the actions and benefits of either fat for more intensive support or clinical use, we need to alter the natural 1.5:1 EPA:DHA ratio found in most omega-3 sources such as fish oil – which is when concentrated supplements are especially useful. Certain forms of omega-3 called ethyl-ester and re-esterified triglyceride give nature a helping hand – allowing us to achieve targeted ratios of specific fatty acids at high concentration and physiologically active doses.
When it comes to fat, there's one type you don’t want to cut back on: omega-3 fatty acids. Two crucial ones -- EPA and DHA -- are primarily found in certain fish. ALA (alpha-linolenic acid), another omega-3 fatty acid, is found in plant sources such as nuts and seeds. Not only does your body need these fatty acids to function, but also they deliver some big health benefits.
In 1964 it was discovered that enzymes found in sheep tissues convert omega−6 arachidonic acid into the inflammatory agent called prostaglandin E2[71] which both causes the sensation of pain and expedites healing and immune response in traumatized and infected tissues.[72] By 1979 more of what are now known as eicosanoids were discovered: thromboxanes, prostacyclins, and the leukotrienes.[72] The eicosanoids, which have important biological functions, typically have a short active lifetime in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. If the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may, however, have deleterious effects.[72] Researchers found that certain omega−3 fatty acids are also converted into eicosanoids, but at a much slower rate. Eicosanoids made from omega−3 fatty acids are often referred to as anti-inflammatory, but in fact they are just less inflammatory than those made from omega−6 fats. If both omega−3 and omega−6 fatty acids are present, they will "compete" to be transformed,[72] so the ratio of long-chain omega−3:omega−6 fatty acids directly affects the type of eicosanoids that are produced.[72]
Heavy metal poisoning by the body's accumulation of traces of heavy metals, in particular mercury, lead, nickel, arsenic, and cadmium, is a possible risk from consuming fish oil supplements.[medical citation needed] Also, other contaminants (PCBs, furans, dioxins, and PBDEs) might be found, especially in less-refined fish oil supplements.[citation needed] However, heavy metal toxicity from consuming fish oil supplements is highly unlikely, because heavy metals selectively bind with protein in the fish flesh rather than accumulate in the oil. An independent test in 2005 of 44 fish oils on the US market found all of the products passed safety standards for potential contaminants.[107][unreliable source?]
Increased EPA levels in the blood and cell membranes effectively regulates inflammatory pathways and reduces total inflammatory ‘load’, so for any inflammatory conditions or concerns, we recommend a phase of pure EPA supplementation for at least 3-6 months. Pre-loading the body with pure EPA (without the opposing actions of DHA for uptake and utilisation) ensures constant replenishment of EPA ’supplies’ to support its high rate of turnover. Since DHA levels remain fairly stable and much lower daily amounts are required, DHA levels can be supported continually through dietary intake, or increased to 250 mg daily in later stages of treatment through supplementation.
A report by the Harvard Medical School studied five popular brands of fish oil, including Nordic Ultimate, Kirkland and CVS. They found that the brands had "negligible amounts of mercury, suggesting either that mercury is removed during the manufacturing of purified fish oil or that the fish sources used in these commercial preparations are relatively mercury-free".[66]
Several recent clinical studies, especially those focusing on the benefits of omega-3 in inflammatory conditions, have investigated the actions of pure-EPA in protecting against excess inflammation in the body. EPA works in several different ways. Firstly, it is the precursor to a number of immune messengers, collectively called ‘eicosanoids’ (series-3 prostaglandins, series-3 thromboxanes and series-5 leukotrienes,) all of which have anti-inflammatory roles.
Oftentimes this could be a result of poor body composition, poor activity levels, or other things, like a low-quality diet. Now, for other people, I do think it’s the case that for people who do not eat fish and for people whose animal products, especially their eggs, are mostly from animals fed grains rather than pasture-raised animals or who don’t eat eggs, I think in those cases there is an argument for fish oil in the sense that those people are probably not going to get enough omega-3 fatty acids, but the better argument might be: Eat pastured eggs or eat fish. Even eating an oily fish like salmon once or twice a week is probably good enough to provide the omega-3 fatty acids that you need. Eating some pastured egg yolks every day is probably good enough to provide for the omega-3 fatty acids that you need.
Not surprising, there are some areas in which both EPA and DHA appear to be equally beneficial. As an example, both are equally effective in reducing triglyceride levels (10). This is probably due to the relatively equivalent activation of the gene transcription factor (PPAR alpha) that causes the enhanced synthesis of the enzymes that oxidize fats in lipoprotein particles. There is also apparently equal activation of the anti-inflammatory gene transcription factor PPAR-gamma (11). Both seem to be equally effective in making powerful anti-inflammatory eicosanoids known as resolvins (12). Finally, although both have no effect on total cholesterol levels, DHA can increase the size of LDL particle to a greater extent than can EPA (10).

Omega-3 is a group of long-chain polyunsaturated fatty acids, perhaps most notably found in fatty fish. As science parses the biological actions of nutrients, it turns out that omega-3 fats do many good things for the body and the brain. Known as an "essential" fatty acid, meaning the body must take it in from food sources, omega-3 is important to human metabolism.
The hypotriglyceridemic effect of fish oil is well established and is related to both dose and baseline triglyceride level. Patients with triglycerides <90 mg/dL will be negligibly affected unless very high doses of omega-3 FA are used.67,68 However, in patients with triglycerides >200 mg/dL, who are treated with 4 g/d of fish oil, a 30% reduction in triglycerides is expected.17,69 For patients with triglycerides >500 mg/dL who are at risk for pancreatitis, the National Cholesterol Education Program Adult Treatment Panel III guidelines recommend using fish oil supplements as an adjunctive therapy to fibrates and nicotinic acid.70 Lovaza capsules have been shown to be effective, safe, and comparable to gemfibrozil in treating triglycerides at this range.71,72 The official label recommendation for Lovaza is for patients with triglycerides >500 mg/dL.73
Humans can convert short-chain omega−3 fatty acids to long-chain forms (EPA, DHA) with an efficiency below 5%.[73][74] The omega−3 conversion efficiency is greater in women than in men, but less studied.[75] Higher ALA and DHA values found in plasma phospholipids of women may be due to the higher activity of desaturases, especially that of delta-6-desaturase.[76]
Dr. Holub has provided the questions and answers for several emails he has received over the years regarding omega-3 fatty acids for health.  If you have a question regarding omega-3, it is likely that Dr. Holub has answered it either here in this section, or elsewhere on the site (e.g. check the scientific overview section for general questions regarding omega-3).  To quickly find your answer, please use our search bar located in the top right section of this page.  After searching our site, and  you still cannot find the answer to your question, we invite you to ask Dr. Holub a question here.
Most leafy green vegetables have significant amounts of omega-3, and spinach is no exception. Despite its villainous reputation, raw spinach actually has a mild flavor, making it an ideal base for salads or a crunchy addition to sandwiches. Many people add spinach to eggs, soups, or pasta dishes without impacting flavor. If you’re dealing with a particularly picky eater, though, try some of the recipes in Jessica Seinfeld’s Deceptively Delicious — her spinach and carrot brownies are tasty, healthy, and chocolaty to boot!

A scientific review published in 2013 looked at omega-3 polyunsaturated fatty acids and prostate cancer prevention. Researchers concluded that there’s a great deal of evidence suggesting that omega-3s have antiproliferative effects – which means they inhibit cancer cell growth – in cancer cell lines, animal models and humans. In addition, the “direct effects on cancer cells” and indirect anti-inflammatory effects on the immune system fighting the cancer likely contribute to the ability of omega-3 fatty acids to inhibit tumor growth. (14)
Fish oil is also extremely beneficial for pregnant women and their children. Throughout pregnancy and also while breastfeeding, a woman’s omega-3 needs are even higher than usual. According to the American Pregnancy Association, most U.S. women are deficient in EPA and especially DHA going into pregnancy and get even more depleted during pregnancy, as the placenta supplies the fetus with DHA from the mother’s tissue. Omega-3 DHA is a critical building block of the fetal brain, eyes and nervous system. Once the baby is born, omega-3s continue to be vital to healthy brain development and immune function. (30)
Dry eye. Higher intake of fish oil from the diet has been linked to a lower risk of dry eye in women. But the effects of fish oil in people with dry eye are inconsistent. Some research shows that fish oil reduces dry eye symptoms such as pain, blurred vision, and sensitivity. But fish oil doesn’t seem to improve other signs and symptoms of dry eye such as tear production and damage to the surface of the eye. Taking fish oil also doesn’t improve signs and symptoms of dry eye when used with other dry eye treatments.
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