Omega-3 fatty acids have been shown to increase platelet responsiveness to subtherapeutic anticoagulation therapies, including aspirin. Recently, it was noted that patient response to aspirin for anticoagulation therapy is widely variable (45), and, thus, the number of patients with a low response to aspirin or aspirin resistance is estimated to range from <1% to 45%, depending on many variables. However, in patients with stable coronary artery disease taking low-dose aspirin, EPA+DHA supplementation has been proven to be as effective as aspirin dose escalation to 325 mg/d for anticoagulation benefits (45). The antiplatelet drug clopidogrel has also been associated with hyporesponsiveness in some patients. This could be attributed to poor patient compliance, differences in genes and platelet reactivity, variability of drug metabolism, and drug interactions. More importantly, in 1 study, patients receiving standard dual antiplatelet therapy (aspirin 75 mg/d and clopidogrel 600-mg loading dose followed by 75 mg/d) were assigned to either EPA+DHA supplementation or placebo. After 1 mo of treatment, the P2Y12 receptor reactivity index (an indicator of clopidogrel resistance) was significantly lower, by 22%, for patients taking EPA+DHA compared with patients taking placebo (P = 0.020) (46).
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.
Dornstauder, B., Suh, M., Kuny, S., Gaillard, F., MacDonald, I., Michael T. Clandinin, M. T., & Sauvé, Y. (2012, June). Dietary docosahexaenoic acid supplementation prevents age-related functional losses and A2E accumulation in the retina. Investigative Ophthalmology and Visual Science. Retrieved from http://iovs.arvojournals.org/article.aspx?articleid=2188773
A, Subgroup meta-analysis of the anxiolytic effect of omega-3 polyunsaturated fatty acids (PUFAs) based on an underlying specific clinical diagnosis or not. The anxiolytic effect of omega-3 PUFAs was not significant in the subgroup of participants without specific clinical conditions (k, 5; Hedges g, –0.008; 95% CI, –0.266 to 0.250; P = .95) but was significant in the subgroup of participants with specific clinical diagnoses (k, 14; Hedges g, 0.512; 95% CI, 0.119-0.906; P = .01). Furthermore, the association of treatment with reduced anxiety symptoms of omega-3 PUFAs were significantly stronger in subgroups with specific clinical diagnoses than in subgroups without specific clinical conditions (P = .03). B, Subgroup meta-analysis of the anxiolytic effect of omega-3 PUFAs based on different mean omega-3 PUFA dosages. The anxiolytic effect of omega-3 PUFAs was not significant in subgroups of mean omega-3 PUFA dosages less than 2000 mg/d (k, 9; Hedges g, 0.457; 95% CI, –0.077 to 0.991; P = .09) but was significant in the subgroup of mean omega-3 PUFA dosage of at least 2000 mg/d (k, 11; Hedges g, 0.213; 95% CI, 0.031-0.395; P = .02).
Two psychiatrists (P.-T.T. and T.-Y.C.) separately performed a systematic literature search of the PubMed, Embase, ProQuest, ScienceDirect, Cochrane Library, ClinicalKey, Web of Science, and ClinicalTrials.gov databases to March 4, 2018. Because we presumed some clinical trials would use investigating scales for some other mood symptoms but also contain symptoms of anxiety, we tried to use some nonspecific medical subject heading terms to include those clinical trials. Therefore, we used the following keywords: omega-3, eicosapentaenoic acid, EPA, DHA, or docosahexaenoic acid; and anxiety, anxiety disorder, generalized anxiety disorder, agoraphobia, panic disorder, or posttraumatic stress disorder. After removing duplicate studies, the same 2 authors screened the search results according to the title and abstract to evaluate eligibility. List of potentially relevant studies were generated for a full-text review. Any inconsistencies were discussed with a third author to achieve final consensus. To expand the list of potentially eligible articles, we performed a manual search of the reference lists of review articles in this area.12,38,39
A healthy balance of dietary omega 6 and omega 3 fatty acids is a prerequisite for normal immune function, cognitive health, and cardiovascular health. Among other factors, sufficient dietary levels of EPA, DHA or other omega 3 fatty acids are also important in the regulation of normal blood lipoprotein and healthy cholesterol metabolism. Fish oil supplements can also lower elevated triglyceride levels, improving cardiovascular health and reducing the risk of heart disease.†
Evidence suggests that omega−3 fatty acids modestly lower blood pressure (systolic and diastolic) in people with hypertension and in people with normal blood pressure. Some evidence suggests that people with certain circulatory problems, such as varicose veins, may benefit from the consumption of EPA and DHA, which may stimulate blood circulation and increase the breakdown of fibrin, a protein involved in blood clotting and scar formation. Omega−3 fatty acids reduce blood triglyceride levels but do not significantly change the level of LDL cholesterol or HDL cholesterol in the blood. The American Heart Association position (2011) is that borderline elevated triglycerides, defined as 150–199 mg/dL, can be lowered by 0.5-1.0 grams of EPA and DHA per day; high triglycerides 200–499 mg/dL benefit from 1-2 g/day; and >500 mg/dL be treated under a physician's supervision with 2-4 g/day using a prescription product.
Due to the anticipated heterogeneity, a random-effects meta-analysis was chosen rather than a fixed-effects meta-analysis because random-effects modeling is more stringent and incorporates an among-study variance in the calculations. The entire meta-analysis procedure was performed on the platform of Comprehensive Meta-analysis statistical software, version 3 (Biostat). Under the preliminary assumption that the scales for anxiety symptoms are heterogeneous among the recruited studies, we chose Hedges g and 95% confidence intervals to combine the effect sizes, in accordance with the manual of the Comprehensive Meta-analysis statistical software, version 3. Regarding the interpretation of effect sizes, we defined Hedges g values 0 or higher as a better association of treatment with reduced anxiety symptoms of omega-3 PUFAs than in controls. For each analysis, a 2-tailed P value less than .05 was considered to indicate statistical significance. When more than 1 anxiety scale was used in a study, we chose the one with the most informative data (ie, mean and standard deviation [SD] before and after treatment). We entered the primary outcome provided in the included articles or obtained from the original authors. As for the variance imputation, we mainly chose the mean and SD before and after treatment. Later, we entered the mean and SD and calculated the effect sizes based on the software option, standardized by post score SD. In the case of studies with 2 active treatment arms, we merged the 2 active treatment arms into 1 group. If these 2 active treatment arms belonged to different subgroups (ie, different PUFA dosage subgroups), we kept them separate. Regarding the numbers of participants counted, we chose intention-to-treat as our priority. If there were insufficient data in the intention to treat group (ie, some studies only provided the changes in anxiety severity in those participants completing trials), we chose instead the per-protocol numbers of participants.
Nonetheless, large population studies with solid data both on the participants’ diets and causes of disease and death bolstered the beliefs that eating fish often was a heart-healthy practice linked to reduced rates of cardiovascular disease. For example, a comprehensive analysis conducted by Dr. Dariush Mozaffarian and Eric Rimm of the Harvard T.H. Chan School of Public Health found that eating two servings of fatty fish a week — equal to about two grams of omega-3 fatty acids — lowered the risk of death from heart disease by more than a third and total deaths by 17 percent.
Fish oil is also used for diabetes, prediabetes, asthma, a movement and coordination disorder called dyspraxia, dyslexia, eczema, autism, obesity, weak bones (osteoporosis), rheumatoid arthritis (RA), osteoarthritis, psoriasis, an autoimmune disease called systemic lupus erythematosus (SLE), multiple sclerosis, HIV/AIDS, cystic fibrosis, gum disease, Lyme disease, sickle cell disease, and preventing weight loss caused by some cancer drugs.