Ample evidence from animal studies supports regular supplementation with omega-3 oils as a means of lowering long-term cardiovascular risk. This may be due to omega-3 fatty acids’ effects on reducing inflammation, lowering triglycerides, reducing blood pressure, improving endothelial function, inducing new blood vessel formation after heart attack or stroke, and favorable modification of obesity-related inflammatory molecules.35-39

Omega AD study, Irving et al. (54) Double-blind, placebo-controlled, randomized 1741 DHA (1.7 g/d) and EPA (0.6 g/d) for 6 mo, then for all subjects (supplementation group and placebo group) Supplementation was associated with positive weight gain and appetite in supplementation group at 6 mo, but not in the placebo group, and for both groups at 12 mo
Human growth and intellectual development – DHA plays a very important role during fetal development, early infancy and old age. High concentrations of DHA are found in the brain and increase 300 to 500 percent in an infant’s brain during the last trimester of pregnancy. Adding DHA to a pregnant mother’s diet may be beneficial for the fetus’s brain development. Elderly people should also take EPA DHA, because as we get older, our bodies form less EPA and DHA, which may cause less mental focus and cognitive function. Taking EPA DHA also may help with mental abnormalities, such as Alzheimer’s disease and dementia.
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.
Heart disease. Eating fish can be effective for keeping people with healthy hearts free of heart disease. People who already have heart disease might also be able to lower their risk of dying from heart disease by eating fish. The picture is less clear for fish oil supplements. For people who already take heart medications such as a "statin" and those who already eat a decent amount of fish, adding on fish oil might not offer any additional benefit.

In total, 19 articles with 19 data sets revealed the main results of the meta-analysis, namely that there was a significantly better association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 19; Hedges g, 0.374; 95% CI, 0.081-0.666; P = .01; Figure 2), with significant heterogeneity (Cochran Q, 178.820; df, 18; I2, 89.934%; P < .001) but no significant publication bias via Egger regression (t, 1.736; df, 17; P = .10) or inspection of the funnel plot (eFigure 2 in the Supplement). According to the trim-and-fill test, there was no need for adjustment for publication bias. The meta-analysis results remained significant after removal of any one of the included studies, which indicated that the significant results are not owing to any single study.
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 studies recruited men and women, some healthy and others with existing illnesses from North America, Europe, Australia and Asia. Participants were randomly assigned to increase their omega 3 fats or to maintain their usual intake of fat for at least a year. Most studies investigated the impact of giving a long-chain omega 3 supplement in a capsule form and compared it to a dummy pill.  Only a few assessed whole fish intake. Most ALA trials added omega 3 fats to foods such as margarine and gave these enriched foods, or naturally ALA-rich foods such as walnuts, to people in the intervention groups, and usual (non-enriched) foods to other participants.
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.

Of great clinical importance, EPA and DHA supplementation during pregnancy has been associated with longer gestation and increased concentrations of EPA and DHA in fetal tissues (21). In 2005, preterm births accounted for 12.7% of all births in the United States, increasing the likelihood of health complications (22). Carrying a baby to term is very important because prematurity is the cause of various infant diseases and can lead to death; preterm delivery is an underlying factor for 85% of the deaths of normally formed infants (23). One mechanism by which EPA and DHA may decrease the incidence of preterm birth is by decreasing prostaglandin E2 and prostaglandin F2α production, therefore reducing inflammation within the uterus, which could be associated with preterm labor (21, 24). Several studies investigated EPA and DHA intake during pregnancy and its correlation with longer gestation. Conclusions were that EPA+DHA supplementation during pregnancy delayed the onset of delivery to term or closer to term; however, supplementation did not delay delivery to the point of being post-term (20, 23, 25). This supports the evidence that EPA+DHA ingestion leads to optimal pregnancy length. EPA+DHA supplementation reduced the HR of preterm delivery by 44% (95% CI: 14–64%) in those who consumed relatively low amounts of fish and 39% (95% CI: 16–56%) in those who consumed medium amounts of fish; however, a level of statistical significance was not met (P = 0.10) (23). The Judge et al. (20) study found that women who had DHA supplementation from gestation week 24 until full-term delivery carried their infants significantly (P = 0.019) longer than did the women in the placebo group. One study found that DHA supplementation after gestation week 21 led to fewer preterm births (<34 wk of gestation) in the DHA group compared with the control group (1.09% vs. 2.25%; adjusted RR, 0.49; 95% CI: 0.25–0.94; P = 0.03). Also, mean birth weight was 68 g heavier (95% CI: 23–114 g; P = 0.003) and fewer infants were of low birth weight in the DHA group compared with the control group (3.41% vs. 5.27%; adjusted RR, 0.65; 95% CI: 0.44–0.96; P = 0.03) (25).


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]
In addition to depression, chronic stress leads to loss of volume of the hippocampus—and also causes enlargement of the amygdala, the portion of the brain that regulates anxiety and anger.24 When rats were supplemented with omega-3s during exposure to stress, they showed lower corticosterone levels (a marker of stress), and improved learning on a maze—indicating that the omega-3s helped preserve memory and reduce anxiety.24
46. Gajos G, Rostoff P, Undas A, Piwowarska W. Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after pci to modify responsiveness to dual antiplatelet therapy) study. J Am Coll Cardiol. 2010;55:1671–8. [PubMed]
As mentioned above, the omega-3 index has been suggested as a predictor of the risk of coronary heart disease and other cardiovascular events. One study on a population in Seattle found that people with low omega-3 index levels were 10 times as likely to die from sudden cardiac death compared to people with higher omega-3 index levels (13). The NIH-funded Framingham study referenced above showed that the people with the highest omega-3 index levels had a 33% reduction in risk of death from any cause compared to the people with the lowest levels (2). In addition, a new study focused on individuals age 25 to 41 found that higher omega-3 index levels were associated with lower blood pressure in healthy adults (14).
Heart rate variability, a possible surrogate outcome for the risk of sudden death, was assessed in a randomized trial of myocardial infarction (MI) survivors with an ejection fraction of 40%. In the 49 patients that were randomized to either fish oil or olive oil, Holter monitor recordings showed an increase in heart rate variability in the fish oil group.31 In a larger cohort assessed in the Japan EPA Lipid Intervention Study (JELIS),32 however, no difference in heart rate variability could be attributed to fish oil.
Corresponding Author: Yutaka J. Matsuoka, MD, PhD, Division of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan (yumatsuo@ncc.go.jp); Kuan-Pin Su, MD, PhD, China Medical University Hospital, No. 2, Yude Road, North District, Taichung City, Taiwan 404 (cobolsu@gmail.com).
Our scientists also focused on each oil’s freshness, measured by the degree of oxidation. Oxidation occurs in two phases: primary (measured by peroxide values) and secondary (measured by p-anisidine values). Total oxidation is formalized into a quantitative score, TOTOX. While Labdoor conducted tests of both primary and secondary oxidation, advances in rancidity testing confirm that added flavors–particularly added citrus flavors prevalent in liquid formulations–skew p-anisidine values and result in false positive outcomes. Until analytical techniques measuring p-anisidine values that are able to account for added flavors are established, Labdoor will use peroxide values as the primary indicator of freshness. All products recorded measurable levels of oxidation, with the average product recording a peroxide values of 3.7 meq/kg. 14/51 products recorded peroxide levels at or above the upper limit (10 meq/kg).

It is great for improving the condition of the dry skin by making it look shiny and vibrant. It is useful in treating various skin problems such as eczema, psoriasis, itching, skin redness, skin lesions, and rashes. In terms of psoriasis, the EPA present in fish oil restricts the growth of pro-inflammatory agents by producing arachidonic acid. Therefore, fish oil can also be applied topically to get relief from psoriasis.
Omega−3 fatty acids are formed in the chloroplasts of green leaves and algae. While seaweeds and algae are the source of omega−3 fatty acids present in fish, grass is the source of omega−3 fatty acids present in grass fed animals.[134] When cattle are taken off omega−3 fatty acid rich grass and shipped to a feedlot to be fattened on omega−3 fatty acid deficient grain, they begin losing their store of this beneficial fat. Each day that an animal spends in the feedlot, the amount of omega−3 fatty acids in its meat is diminished.[135]
Tanaka, K., Ishikawa, Y., Yokoyama, M., Origasa, H., Matsuzaki, M., Saito, Y., Matsuzawa, Y., Sasaki, J., Oikawa, S., Hishida, H., Itakura, H., Kita, T., Kitabatake, A., Nakaya, N., Sakata, T., Shimada, K., and Shirato, K. Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: subanalysis of the JELIS trial. Stroke 2008;39(7):2052-2058. View abstract.
Metagenics offers a wide range of educational opportunities including webinars, group meetings, and seminars as part of our commitment to continuing functional medicine education. Our goal is to give our practitioners further insight to help address their patients’ unique health needs for a higher level of personalized, lifetime wellness care. We have been sharing this ever-growing body of nutritional and lifestyle research for over 25 years.
Jump up ^ Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J (July 2006). "n−3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review". The American Journal of Clinical Nutrition. 84 (1): 5–17. doi:10.1093/ajcn/84.1.5. PMID 16825676.
Although there are no randomized data on fish oil consumption and protection from sudden death, observational studies have linked omega-3 FA with the prevention of sudden death. In a population-based, case-control study of sudden cardiac death victims, the mean red blood cell membrane omega-3 FA level of the lowest quartile, when compared with the mean level of the third quartile, was associated with a relative risk reduction of 70%.33 A similar finding was appreciated in a nested, prospective, case-control study of the Physician Health Study cohort of 22,000 healthy males. In the 119 patients that succumbed to sudden death, baseline omega-3 FA blood levels were significantly lower than in matched controls.34 Finally, in an analysis of data from the Nurses Health Study, a cohort study of 84,688 women, an inverse association was shown between fish consumption and CAD-related death. The investigators concluded that the reduction in CAD deaths was likely due to a reduction in sudden deaths, as there was no difference in the rate of MI when comparing high and low fish consumption.35
Typical Western diets provide ratios of between 10:1 and 30:1 (i.e., dramatically higher levels of omega−6 than omega−3).[92] The ratios of omega−6 to omega−3 fatty acids in some common vegetable oils are: canola 2:1, hemp 2–3:1,[93] soybean 7:1, olive 3–13:1, sunflower (no omega−3), flax 1:3,[94] cottonseed (almost no omega−3), peanut (no omega−3), grapeseed oil (almost no omega−3) and corn oil 46:1.[95]
The three types of omega−3 fatty acids involved in human physiology are α-linolenic acid (ALA), found in plant oils, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both commonly found in marine oils.[2] Marine algae and phytoplankton are primary sources of omega−3 fatty acids. Common sources of plant oils containing ALA include walnut, edible seeds, clary sage seed oil, algal oil, flaxseed oil, Sacha Inchi oil, Echium oil, and hemp oil, while sources of animal omega−3 fatty acids EPA and DHA include fish, fish oils, eggs from chickens fed EPA and DHA, squid oils, and krill oil. Dietary supplementation with omega−3 fatty acids does not appear to affect the risk of death, cancer or heart disease.[4][5] Furthermore, fish oil supplement studies have failed to support claims of preventing heart attacks or strokes or any vascular disease outcomes.[6][7]

Whilst EPA and DHA are both considered to be important regulators of immunity, platelet aggregation and inflammation, their health-influencing by-products arise from very different pathways and their effects in the body differ. DHA is the most abundant omega-3 fatty acid in cell membranes, present in all organs and most abundant in the brain and retina, playing an important structural role. EPA is present structurally only in minute quantities, always being utilised and under constant demand to be replaced. Whilst DHA provides mainly a structural role, it is becoming evident that EPA may be the dominant functional fatty acid out of the two in many areas of health and especially in inflammatory conditions.
Fish oil is useful in the treatment of arthritis, rheumatism, Raynaud’s symptoms and similar conditions. Using the fish oil can help in reducing the need for large dosages of NSAIDs (non-steroidal anti-inflammatory drugs). The Royal Adelaide Hospital and the University of Newcastle, located in Australia, have reported that fish oil has shown positive effects in the treatment of arthritis. In cases of osteoarthritis, fish oil can be helpful in reducing the impact of enzymes that destroy cartilage.

Given the wide-ranging importance and benefits of marine omega-3 fatty acids, it is important to eat fish or other seafood one to two times per week, particularly fatty (dark meat) fish that are richer in EPA and DHA. This is especially important for women who are pregnant or hoping to become pregnant and nursing mothers. From the third trimester until the second year of life, a developing child needs a steady supply of DHA to form the brain and other parts of the nervous system. Many women shy away from eating fish because of concerns that mercury and other possible contaminants might harm their babies, (9) yet the evidence for harm from lack of omega-3 fats is far more consistent, and a balance of benefit vs. risk is easily obtained. (To learn more about the controversy over contaminants in fatty fish, read Fish: Friend or Foe.)
From the time of your pregnancy through your child's later life, omega-3 fats DHA and EPA have a radically important role in her brain health and other functions. I recommend supplementing with krill oil before and during pregnancy, and while you breastfeed. Babies receive DHA through your breast milk, so continuing breastfeeding through the first year will give your child a great headstart for health and success.
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.
"Fish is still the mainstay of the diet in many parts of the world where there is very little heart disease," he says. "I think when you replace higher fat foods and highly processed foods with fish there is going to be some benefit.'' So it may be that by substituting fish for red meats, bacon and luncheon meats, and similar high-fat foods, you are making a change that will lead to improving your health outcomes, he says.
Pregnancy and breast-feeding: Fish oil is LIKELY SAFE when taken by mouth appropriately. Taking fish oil during pregnancy does not seem to affect the fetus or baby while breast-feeding. Women who are pregnant or who may become pregnant, and nursing mothers should avoid shark, swordfish, king mackerel, and tilefish (also called golden bass or golden snapper), as these may contain high levels of mercury. Limit consumption of other fish to 12 ounces/week (about 3 to 4 servings/week). Fish oil is POSSIBLY UNSAFE when dietary sources are consumed in large amounts. Fatty fish contain toxins such as mercury.
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