Several small studies have shown that combination therapy with fish oil and HMG CoA reductase inhibitors is safe.56–61 The largest trial to date, the JELIS trial,32 was an open label trial of 18,645 Japanese adults with hypercholesterolemia who were randomized to a standard statin regimen or a fish oil formulation containing 1.8 g of EPA added to a statin medication. The cohort was made up mostly of postmenopausal, nonobese women with a 15% to 20% incidence of diabetes, tobacco use, or CAD. The primary outcome of any major cardiovascular event, at a mean of 4.6 years, was moderately reduced by a relative risk reduction of 26%. Both unstable angina and nonfatal MI were reduced, but no change was seen in sudden death. Overall, the findings were remarkable because at baseline approximately 90% of Japanese consumed at least 900 mg of EPA and DHA per day.62 The rates of cancer, joint pain, lumbar pain, or muscle pain were similar in the 2 groups. There was a similar rate of increase in measures of creatine phosphokinase, but more patients had an increase in aspartate aminotransferase levels (0.6% vs. 0.4%) in the fish oil group. The rate of bleeding was 1.1% in the fish oil combination group versus 0.6% in the HMG–CoA reductase inhibitor group.

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]

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Ramakrishnan, U., Stein, A. D., Parra-Cabrera, S., Wang, M., Imhoff-Kunsch, B., Juarez-Marquez, S., Rivera, J., and Martorell, R. Effects of docosahexaenoic acid supplementation during pregnancy on gestational age and size at birth: randomized, double-blind, placebo-controlled trial in Mexico. Food Nutr Bull 2010;31(2 Suppl):S108-S116. View abstract.
The supplements contain omega-3 fatty acids, the polyunsaturated oils prominent in fatty cold water fish like salmon, sardines and mackerel. In many observational studies, people who regularly consumed fish two or more times a week were less likely to suffer heart attacks, strokes and cardiovascular deaths than those who ate fish infrequently or not at all.
Jump up ^ Heartney, Eleanor (2007). "Zhang Huan: Becoming the Body". Zhang Huan: Altered States. Charta and Asia Society. ISBN 978-8881586417. Retrieved 2014-10-23. This becomes abundantly clear in the work of Chinese body artist Zhang Huan. In the course of his career, Zhang Huan has subjected himself to painful trials: sitting motionless for hours in an outhouse covered in honey and fish oil while flies crawled over his body [...].
Nielsen, G. L., Faarvang, K. L., Thomsen, B. S., Teglbjaerg, K. L., Jensen, L. T., Hansen, T. M., Lervang, H. H., Schmidt, E. B., Dyerberg, J., and Ernst, E. The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial. Eur J Clin Invest 1992;22(10):687-691. View abstract.

Fish oil supplements came under scrutiny in 2006, when the Food Standards Agency in the UK and the Food Safety Authority of Ireland reported PCB levels that exceeded the European maximum limits in several fish oil brands,[60][61] which required temporary withdrawal of these brands. To address the concern over contaminated fish oil supplements, the International Fish Oil Standards (IFOS) Program, a third-party testing and accreditation program for fish oil products, was created by Nutrasource Diagnostics Inc. in Guelph, Ontario, Canada.[62]
The chemical structure of eicosapentaenoic acid and docosahexaenoic acid. Eicosapentaenoic acid consists of 20 carbons (C20) with 5 double bonds, and the last unsaturated carbon is located third from the methyl end (n-3). Do-cosahexaenoic acid consists of 22 carbons (C22) with 6 double bonds, and also with the3 last unsaturated carbon located third from the methyl end (n-3). Adapted with permission from Frishman et al, eds. Cardiovascular Pharmacotherapeutics. New York, NY: McGraw Hill; 2003.3
Peroxides can be produced when fish oil spoils. A study commissioned by the government of Norway concluded there would be some health concern related to the regular consumption of oxidized (rancid) fish/marine oils, particularly in regards to the gastrointestinal tract, but there is not enough data to determine the risk. The amount of spoilage and contamination in a supplement depends on the raw materials and processes of extraction, refining, concentration, encapsulation, storage and transportation.[51] ConsumerLab.com reports in its review that it found spoilage in test reports it ordered on some fish oil supplement products.[52]
Jump up ^ Siscovick DS, Barringer TA, Fretts AM, Wu JH, Lichtenstein AH, Costello RB, Kris-Etherton PM, Jacobson TA, Engler MB, Alger HM, Appel LJ, Mozaffarian D (2017). "Omega−3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association". Circulation. 135 (15): e867–84. doi:10.1161/CIR.0000000000000482. PMID 28289069.
Joensen, A. M., Schmidt, E. B., Dethlefsen, C., Johnsen, S. P., Tjonneland, A., Rasmussen, L. H., and Overvad, K. Dietary intake of total marine n-3 polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid and docosapentaenoic acid and the risk of acute coronary syndrome - a cohort study. Br J Nutr 2010;103(4):602-607. View abstract.
During pregnancy and breastfeeding, eating 8 to 12 ounces per week of fish and other seafood may improve your baby’s health. However, it is important to choose fish that are higher in EPA and DHA and lower in mercury. Examples are salmon, herring, sardines, and trout. It is not clear whether taking dietary supplements containing EPA and DHA during pregnancy or breastfeeding affects a baby’s health or development. However, some studies show that taking these supplements may slightly increase a baby’s weight at birth and the length of time the baby is in the womb, both of which may be beneficial. Breast milk contains DHA. Most commercial infant formulas also contain DHA.
In your final paragraph, you suggest that a ratio of 2:1 EPA/DHA maybe best for reducing inflammation. Are you suggesting using two separate products to obtain that ratio? I can't see how it is achieveable through standard omega-3 products. Good fish oil brands are typically 60% or higher EPA, but never reach a 2:1 ratio in my product searches. According to case studies (link below), 1 gram of EPA per day (60% or more of the total omega-3 content) is sufficient and the highest efficacy.
Fortier, M., Tremblay-Mercier, J., Plourde, M., Chouinard-Watkins, R., Vandal, M., Pifferi, F., Freemantle, E., and Cunnane, S. C. Higher plasma n-3 fatty acid status in the moderately healthy elderly in southern Quebec: higher fish intake or aging-related change in n-3 fatty acid metabolism? Prostaglandins Leukot.Essent.Fatty Acids 2010;82(4-6):277-280. View abstract.
Several other analyses of the evidence have been done in the last few years (2012 or later), and like the 2018 analysis and the AHRQ report, most found little or no evidence for a protective effect of omega-3 supplements against heart disease. However, some earlier analyses suggested that omega-3s could be helpful. The difference between the newer conclusions and the older ones may reflect two changes over time: 

Makrides et al. (25) Double-blind, placebo-controlled, randomized 2399 (n = 1197 supplemented, n = 1202 placebo; 726 children were followed up with) DHA (fish-oil capsules providing 800 mg/d DHA) Supplementation did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in offspring during early childhood


The conversion of ALA to EPA and further to DHA in humans has been reported to be limited, but varies with individuals.[79][80] Women have higher ALA-to-DHA conversion efficiency than men, which is presumed[81] to be due to the lower rate of use of dietary ALA for beta-oxidation. One preliminary study showed that EPA can be increased by lowering the amount of dietary linoleic acid, and DHA can be increased by elevating intake of dietary ALA.[82]
Fearon, K. C., Von Meyenfeldt, M. F., Moses, A. G., Van Geenen, R., Roy, A., Gouma, D. J., Giacosa, A., Van Gossum, A., Bauer, J., Barber, M. D., Aaronson, N. K., Voss, A. C., and Tisdale, M. J. Effect of a protein and energy dense n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut 2003;52(10):1479-1486. View abstract.
The omega-3 PUFA EPA and DHA are important throughout life and are a dietary necessity found predominantly in fish and fish-oil supplements. The omega-3 fatty acids EPA and DHA are essential for proper fetal development, and supplementation during pregnancy has also been linked to decreased immune responses in infants including decreased incidence of allergies in infants. Omega-3 fatty acid consumption has been associated with improved cardiovascular function in terms of antiinflammatory properties, PAD, reduced major coronary events, and improved antiplatelet effects in the face of aspirin resistance or clopidogrel hyporesponsiveness. Patients with AD have been shown to be deficient in DHA, and supplementing them with EPA+DHA not only reverses this deficiency, but may also improve cognitive functioning in patients with very mild AD. With increasing rates of pediatric allergies, cardiovascular disease, and AD in the United States, EPA and DHA may be a safe and inexpensive link to a healthier life. Further research should be conducted in humans to assess a variety of clinical outcomes including quality of life and mental status. In addition, because potent lipid mediator metabolites of EPA and DHA are of great interest currently, their influence on these important outcomes should be assessed because current evidence suggests that their antiinflammatory and tissue-protective effects are nearly 1000 times greater than those of EPA and DHA (7).
Irving, G. F., Freund-Levi, Y., Eriksdotter-Jonhagen, M., Basun, H., Brismar, K., Hjorth, E., Palmblad, J., Vessby, B., Vedin, I., Wahlund, L. O., and Cederholm, T. Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer's disease: the omega-3 Alzheimer's disease study. J Am Geriatr Soc 2009;57(1):11-17. View abstract.

Schilling, J., Vranjes, N., Fierz, W., Joller, H., Gyurech, D., Ludwig, E., Marathias, K., and Geroulanos, S. Clinical outcome and immunology of postoperative arginine, omega-3 fatty acids, and nucleotide-enriched enteral feeding: a randomized prospective comparison with standard enteral and low calorie/low fat i.v. solutions. Nutrition 1996;12(6):423-429. 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.
Several small studies have shown that combination therapy with fish oil and HMG CoA reductase inhibitors is safe.56–61 The largest trial to date, the JELIS trial,32 was an open label trial of 18,645 Japanese adults with hypercholesterolemia who were randomized to a standard statin regimen or a fish oil formulation containing 1.8 g of EPA added to a statin medication. The cohort was made up mostly of postmenopausal, nonobese women with a 15% to 20% incidence of diabetes, tobacco use, or CAD. The primary outcome of any major cardiovascular event, at a mean of 4.6 years, was moderately reduced by a relative risk reduction of 26%. Both unstable angina and nonfatal MI were reduced, but no change was seen in sudden death. Overall, the findings were remarkable because at baseline approximately 90% of Japanese consumed at least 900 mg of EPA and DHA per day.62 The rates of cancer, joint pain, lumbar pain, or muscle pain were similar in the 2 groups. There was a similar rate of increase in measures of creatine phosphokinase, but more patients had an increase in aspartate aminotransferase levels (0.6% vs. 0.4%) in the fish oil group. The rate of bleeding was 1.1% in the fish oil combination group versus 0.6% in the HMG–CoA reductase inhibitor group.
A 2009 metastudy found that patients taking omega-3 supplements with a higher EPA:DHA ratio experienced fewer depressive symptoms. The studies provided evidence that EPA may be more efficacious than DHA in treating depression. However, this metastudy concluded that due to the identified limitations of the included studies, larger, randomized trials are needed to confirm these findings.[40]
Weight loss. Some research shows that eating fish improves weight loss and decreases blood sugar in people who are overweight with high blood pressure. Early research also shows that taking a specific fish oil supplement (Hi-DHA, NuMega) lowers body fat when combined with exercise. But other evidence suggests that taking another specific fish oil supplement (Lovaza) does not lower body weight in overweight people.
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