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.

Fish oil has been shown to have a direct electrophysiological effect on the myocardium. Initial experience with animal ischemia models demonstrated that the ventricular fibrillation threshold was increased in both animals fed or infused with omega-3 FA.23,24 This progressed to a demonstration, on a cellular and ion channel level, that omega-3 FA reduce both sodium currents and L-type calcium currents.25–29 It is hypothesized that during ischemia, a reduction in the sodium ion current protects hyperexcitable tissue, and a reduction in the calcium ion current reduces arrhythmogenic depolarizing currents.30
16. Saito Y, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, et al. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis. 2008;200:135–40. [PubMed]
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Both omega−6 and omega−3 fatty acids are essential: humans must consume them in their diet. Omega−6 and omega−3 eighteen-carbon polyunsaturated fatty acids compete for the same metabolic enzymes, thus the omega−6:omega−3 ratio of ingested fatty acids has significant influence on the ratio and rate of production of eicosanoids, a group of hormones intimately involved in the body's inflammatory and homeostatic processes, which include the prostaglandins, leukotrienes, and thromboxanes, among others. Altering this ratio can change the body's metabolic and inflammatory state.[16] In general, grass-fed animals accumulate more omega−3 than do grain-fed animals, which accumulate relatively more omega−6.[86] Metabolites of omega−6 are more inflammatory (esp. arachidonic acid) than those of omega−3. This necessitates that omega−6 and omega−3 be consumed in a balanced proportion; healthy ratios of omega−6:omega−3, according to some authors, range from 1:1 to 1:4.[87] Other authors believe that a ratio of 4:1 (4 times as much omega−6 as omega−3) is already healthy.[88][89] Studies suggest the evolutionary human diet, rich in game animals, seafood, and other sources of omega−3, may have provided such a ratio.[90][91]
And in osteoarthritis, when a DHA/EPA formulation was added to chondroitin sulfate, people experienced more complete relief of symptoms such as stiffness and pain. One study found a significant increase in walking speed in people who supplemented with fish oil versus those who did not.79,80 As with the beneficial results seen in people with bone loss, these positive findings may have been the result of the decreased inflammatory destruction of joint cartilage.81
Animal studies show potent reduction of liver fat stores, glucose levels, and cholesterol levels in mice supplemented with krill oil while being fed a high fat diet.64,65 While many of these effects are seen with fish oil as well, studies show that krill oil, with its unique phospholipid structure, had the added benefit of increasing fat-burning in mitochondria while reducing new glucose production in the liver.66,67 As with so many other complex disease processes, utilizing multiple pathways to reduce disease is a highly effective strategy.67

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.

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.
High blood pressure. Fish oil seems to slightly lower blood pressure in people with moderate to very high blood pressure. Some types of fish oil might also reduce blood pressure in people with slightly high blood pressure, but results are inconsistent. Fish oil seems to add to the effects of some, but not all, blood pressure-lowering medications. However, it doesn't seem to reduce blood pressure in people with uncontrolled blood pressure who are already taking blood pressure-lowering medications.