Moertl, D., Hammer, A., Steiner, S., Hutuleac, R., Vonbank, K., and Berger, R. Dose-dependent effects of omega-3-polyunsaturated fatty acids on systolic left ventricular function, endothelial function, and markers of inflammation in chronic heart failure of nonischemic origin: a double-blind, placebo-controlled, 3-arm study. Am.Heart J. 2011;161(5):915-919. View abstract.
Dry eye disease occurs when tears don’t provide enough moisture, causing eye discomfort and vision problems. Some studies show that getting more omega-3s from foods or supplements—mainly EPA and DHA—helps relieve symptoms of dry eye disease. But a large, recent study found that the symptoms of people with dry eye disease who took fish oil supplements of 2,000 mg EPA plus 1,000 mg DHA daily for 1 year did not improve any more than those who took a placebo (a dummy pill). More research on the effects of omega-3s on dry eye disease is needed.

In another study, Australian researchers looked at whether giving infants added omega-3 fatty acids might improve health,4 including reducing their risk for heart disease. They gave 420 infants either an omega 3 supplement or olive oil from birth through six months, then revisited that at age 5 years to see if either group appeared healthier from a heart risk point of view.
To reach the required dose of EPA for treating certain conditions such as depression, CVD or CFS/ME you would need to take approximately 1-2 grams of ‘free EPA’ daily. Even with a concentrated omega-3 fish oil supplement, offering 180 mg excess EPA over DHA, this would require 10-20 capsules daily – significant in terms of volume and cost, and not efficient in terms of uptake in the body as our capacity for fat absorption is limited. The most effective and efficient way to ensure high EPA uptake in the body rapidly is to supplement with pure EPA for a minimum of 3-6 months.
Retinol (Vitamin A) B vitamins: Thiamine (B1) Riboflavin (B2) Niacin (B3) Pantothenic acid (B5) Pyridoxine (B6) Biotin (B7) Folic acid (B9) Cyanocobalamin (B12) Ascorbic acid (Vitamin C) Ergocalciferol and Cholecalciferol (Vitamin D) Tocopherol (Vitamin E) Naphthoquinone (Vitamin K) Calcium Choline Chromium Cobalt Copper Fluorine Iodine Iron Magnesium Manganese Molybdenum Phosphorus Potassium Selenium Sodium Sulfur Zinc
Many studies show that eating fatty fish and other types of seafood as part of a healthy eating pattern helps keep your heart healthy and helps protect you from many heart problems. Getting more EPA or DHA from foods lowers triglyceride levels, for example. Omega-3 dietary supplements can also help lower triglyceride levels, but it is not clear whether omega-3 supplements protect you from most heart problems.
Krill oil is joining the toolkit for fighting arthritis, thanks to its exceptional anti-inflammatory properties resulting from its phospholipid form of omega-3s. A study in mice with experimental arthritis showed that krill oil supplements reduced arthritis scores and markedly diminished joint swelling. When examined under a microscope, the animals’ joints were remarkably free of inflammatory infiltrates of immune system cells.85
When taking fish oil, more is not always better. Remember that you want it to stay in a balanced ratio with omega-6 fats. For most people, I recommend a 1,000-milligram dose of fish oil daily as a good amount and the most scientifically studied dosage. I highly recommend not taking more than that unless directed to under the supervision of a doctor.
While fish for dinner is one way to get EPA and DHA, most people don’t eat the suggested two to three servings of oily fish per week to reap the benefits of omega-3s. What’s more, there are extremely few food sources, aside from fish, that naturally provide EPA and DHA. With all the benefits that can come from fish oil, it’s no surprise that these supplements are increasing in popularity.

Cardiovascular disease is the cause of 38% of all deaths in the United States, many of which are preventable (28). Chronic inflammation is thought to be the cause of many chronic diseases, including cardiovascular disease (29). EPA and DHA are thought to have antiinflammatory effects and a role in oxidative stress (30) and to improve cellular function through changes in gene expression (31). In a study that used human blood samples, EPA+DHA intake changed the expression of 1040 genes and resulted in a decreased expression of genes involved in inflammatory and atherogenesis-related pathways, such as nuclear transcription factor κB signaling, eicosanoid synthesis, scavenger receptor activity, adipogenesis, and hypoxia signaling (31). Circulating markers of inflammation, such as C-reactive protein (CRP), TNF α, and some ILs (IL-6, IL-1), correlate with an increased probability of experiencing a cardiovascular event (32). Inflammatory markers such as IL-6 trigger CRP to be synthesized by the liver, and elevated levels of CRP are associated with an increased risk of the development of cardiovascular disease (33). A study of 89 patients showed that those treated with EPA+DHA had a significant reduction in high-sensitivity CRP (66.7%, P < 0.01) (33). The same study also showed a significant reduction in heat shock protein 27 antibody titers (57.69%, P < 0.05), which have been shown to be overexpressed in heart muscle cells after a return of blood flow after a period of ischemia (ischemia-reperfusion injury) and may potentially have a cardioprotective effect (33).

Omega 3 fatty acids are monounsaturated fats that come from food sources—primarily cold water fish (eg, salmon, trout, tuna, mackerel, and herring)—that contain EPA (eicosapentaenoic acid) and docosahexaenoic acid (DHA). Other fatty acids are derived from plant-derived sources of food—including nuts (especially walnuts) and seeds (eg, flax, chia, sunflower)—that have primarily ALA (alpha-linolenic acid).

Several studies confirmed the benefit of omega-3 supplementation during pregnancy in terms of proper development of the brain and retina. Of the 2 most important long-chain omega-3 fatty acids, EPA and DHA, DHA is the more important for proper cell membrane function and is vital to the development of the fetal brain and retina (17). During the third trimester, vast amounts of DHA accumulate in fetal tissue (20). The 2 most infiltrated fetal areas include the retina and brain, which may correlate with normal eyesight and brain function (19). A study by Judge et al. (20) found that children whose mothers had taken DHA supplementation during pregnancy (n = 29) had significantly better problem-solving skills at 9 mo old (P = 0.017) than those whose mothers had not taken DHA supplementation during pregnancy (n = 15). Another study provided a cognitive assessment of children 2.5 y after maternal EPA+DHA supplementation during pregnancy from 20 wk of gestation until delivery (n = 33) compared with children in a placebo group (n = 39). Children in the EPA + DHA–supplemented group attained significantly higher scores for eye and hand coordination [mean score, 114 (SD 10.2] than those in the placebo group [mean score, 108 (SD 11.3)] (P = 0.021, adjusted P = 0.008) (19).
Flaxseed (or linseed) (Linum usitatissimum) and its oil are perhaps the most widely available botanical source of the omega−3 fatty acid ALA. Flaxseed oil consists of approximately 55% ALA, which makes it six times richer than most fish oils in omega−3 fatty acids.[126] A portion of this is converted by the body to EPA and DHA, though the actual converted percentage may differ between men and women.[127]
The DART study, published in 1989, was the first randomized trial to show the efficacy of fish oil on CAD.37 In the trial, 2033 post-MI patients were randomized to receive 3 types of diets: a diet that was either high in cereal fiber, polyunsaturated fat, or fish oil. The fish oil group consumed 200 to 400 g/wk of fatty fish (2 portions of fish per week) or 0.5 g/d of Maxepa fish oil supplement. At 2 years, the primary end point of all-cause mortality was reduced by 29% in the fish oil group, whereas no improvement was seen in the other dietary advice groups.

Australian researchers published results of a study examining the effects of fish oil on weight loss in combination with diet and exercise in the May 2007 issue of American Journal of Clinical Nutrition. The results show that a combination of fish oil supplements and regular exercise can reduce body fat while also improving heart and metabolic health. The fish supplementation group had lowered triglycerides, increased HDL cholesterol and improved blood flow. Overall, adding fish oil to a current exercise program (and a overall healthy lifestyle) looks like it can decrease body fat as well as cardiovascular disease risk. (32)
The evidence that fish oil consumption should be used for primary prevention of CAD is based on observational studies. The only randomized trial for primary prevention, the JELIS trial, showed a moderate relative risk reduction and was conducted in a very specific group. Nevertheless, to date, there has been no strong signal suggesting any serious adverse effects of having high DHA and EPA oils in the diet. We agree with the national guidelines that one should consume moderate amounts of fish oil— either in supplement or through the dietary intake of fatty fish with low mercury levels.
EPA is the precursor to DHA in the body and can be converted to DHA with the enzyme delta-6 desaturase, but this process is inefficient in many people (much like the inefficiency of short-chain omega-3s to long-chain). For those individuals taking pure EPA products as well as those taking our EPA-rich products, we still recommend eating oily fish at least once each week to provide a natural source of DHA. Fish provides a unique nutritional package, supplying the diet with important amino acids (the building blocks of proteins) and antioxidants, including vitamins and minerals needed to process fats, so eating fish will also support the natural enzyme-dependent EPA to DHA conversion.
The systematic review suggests that eating more ALA through food or supplements probably has little or no effect on cardiovascular deaths or deaths from any cause. However, eating more ALA probably reduces the risk of heart irregularities from 3.3 to 2.6%. The review team found that reductions in cardiovascular events with ALA were so small that about 1000 people would need to increase consumption of ALA for one of them to benefit. Similar results were found for cardiovascular death. They did not find enough data from the studies to be able to measure the risk of bleeding or blood clots from using ALA.
Not all forms of fish oil may be equally digestible. Of four studies that compare bioavailability of the glyceryl ester form of fish oil vs. the ethyl ester form, two have concluded the natural glyceryl ester form is better, and the other two studies did not find a significant difference. No studies have shown the ethyl ester form to be superior, although it is cheaper to manufacture.[114][115]
Weak bones (osteoporosis). Research suggests that taking fish oil alone or together with calcium and evening primrose oil slows the rate of bone loss and increases bone density at the thigh bone (femur) and spine in elderly people with osteoporosis. But taking fish oil does not slow bone loss in older people with osteoarthritis in the knee but without weak bones.