^ Jump up to: a b c Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, Geleijnse JM, Rauch B, Ness A, Galan P, Chew EY, Bosch J, Collins R, Lewington S, Armitage J, Clarke R (March 2018). "Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals". JAMA Cardiology. 3 (3): 225–34. doi:10.1001/jamacardio.2017.5205. PMC 5885893. PMID 29387889.

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).
Consumers of oily fish should be aware of the potential presence of heavy metals and fat-soluble pollutants like PCBs and dioxins, which are known to accumulate up the food chain. After extensive review, researchers from Harvard's School of Public Health in the Journal of the American Medical Association (2006) reported that the benefits of fish intake generally far outweigh the potential risks.

To evaluate the potential placebo effect, we made further subgrouping analyses. In the subgroups of studies using placebo controls, the omega-3 PUFAs still revealed a consistent positive anxiolytic association with anxiety symptoms. These phenomena meant that the anxiolytic effect of omega-3 PUFAs is probably not entirely owing to the placebo effect.

The European Journal of Neuroscience published a study in 2013 showing that fish oil reversed all anxiety-like and depression-like behavior changes induced in rats. This is an interesting study because it stresses the importance of supplementing with fish oil at “critical periods of brain development.” (10) This is exactly why I recommend giving fish oil to our kids from early on to help them so they won’t develop anxiety or depression later in life.

High levels of the oils in blood samples were linked with a 71 per cent increased risk of developing an aggressive and dangerous form of prostate cancer, according to the research. That study, if I recall correctly, mentioned concern about men eating fish more than a certain number of times a week having a 54% increased risk of developing prostate cancer.

Dioxins and PCBs may be carcinogenic at low levels of exposure over time. These substances are identified and measured in one of two categories, dioxin-like PCBs and total PCBs. While the U.S. FDA has not set a limit for PCBs in supplements, the Global Organization for EPA and DHA (GOED) has established a guideline allowing for no more than 3 picograms of dioxin-like PCBs per gram of fish oil. In 2012, samples from 35 fish oil supplements were tested for PCBs. Trace amounts of PCBs were found in all samples, and two samples exceeded the GOED‘s limit.[52] Although trace amounts of PCBs contribute to overall PCB exposure, Consumerlab.com claims the amounts reported by tests it ordered on fish oil supplements are far below those found in a single typical serving of fish.[52]

Heterogeneity was examined using the Q statistic and the corresponding P values,41 and the I2 statistic was used to evaluate the proportion of variation resulting from among-study differences. Any possible publication bias was detected with both funnel plots and Egger regression in the main part of the meta-analysis.42 By using Duval and Tweedie’s trim-and-fill test, we adjusted the effect sizes for potential publication bias if there was evidence of publication bias detected by this test in the Comprehensive Meta-analysis statistical software, version 3.43 To investigate the potential confounding effects of any outliers within the recruited studies, sensitivity testing was conducted with the 1-study removal method to detect the potential outliers.44
The differing actions of EPA and DHA, together with their competitive uptake, help to explain why studies that attempt to use standard fish oil therapeutically (where DHA and EPA are combined, in a natural ratio of approximately 1.5:1) are either less beneficial than expected, or even completely ineffective. Standard EPA/DHA fish oils are more suitable for everyday wellbeing, to compensate for a lack of fish in the diet and to meet a suggested intake.
Finally, in order for AA to be converted into inflammatory products it must be released from phospholipids (part of the cell membrane) using the enzyme phospholipase A2 and then converted by the enzyme cyclooxygenase. EPA utilises both of these enzymes, so if EPA levels are increased in the diet, it attracts enzyme away from AA to EPA – again giving rise to anti-inflammatory products instead of inflammatory ones.

AD is a devastating disease for which there are limited treatment options and no cure. Memory loss is an early indicator of the disease, which is progressive, and leads to the inability of the patient to care for him- or herself and eventually to death (47). Currently, the number of individuals with AD is estimated to be 26.6 million and is expected to increase to 106.2 million by 2050 (48). There have been many studies conducted regarding the use of omega-3 fatty acid supplementation and AD (Table 2). DHA is present in large amounts in neuron membrane phospholipids, where it is involved in proper function of the nervous system, which is why it is thought to play a role in AD (49). A case-control study consisting of 148 patients with cognitive impairment [Mini-Mental State Examination (MMSE) score <24] and 45 control patients (MMSE score ≥24) showed that serum cholesteryl ester-EPA and -DHA levels were significantly lower (P < 0.05 and P < 0.001, respectively) in all MMSE score quartiles of patients with AD compared with control values (49). Another study found that a diet characterized by higher intakes of foods high in omega-3 fatty acids (salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, dark and green leafy vegetables), and a lower intake of foods low in omega-3 fatty acids (high-fat dairy products, red meat, organ meat, butter) was strongly associated with a lower AD risk (50). Image analysis of brain sections of an aged AD mouse model showed that overall plaque burden was significantly reduced by 40.3% in mice with a diet enriched with DHA (P < 0.05) compared with placebo. The largest reductions (40–50%) were seen in brain regions that are thought to be involved with AD, the hippocampus and parietal cortex (51). A central event in AD is thought to be the activation of multiple inflammatory cells in the brain. Release of IL-1B, IL-6, and TNF α from microglia cells may lead to dysfunction of the neurons in the brain (52). In 1 study, AD patients treated with EPA+DHA supplementation increased their plasma concentrations of EPA and DHA, which were associated with reduced release of inflammatory factors IL-1B, IL-6, and granulocyte colony–stimulating factor from peripheral blood mononuclear cells (53).
Thanks for the informative article. You mentioned that those taking high doses of DHA should supplement it with trace amounts of GLA. What GLA source would you recommend, and how much per day? I will be taking around 3400 mg of epa and 2200 mg DHA per day. I've heard that Borage Oil is more potent in GLA than evening primrose, but that it can lead to increased clotting and increased risk of heart attack, stroke, etc due to increased thromboxane B2. The main reason I want to stay away from the primrose is because it is extremely rich in linoleic acid. Thanks.
Cancer. Research on the effects of fish oil in preventing cancer has produced conflicting results. Some population research suggests that eating fish or having higher blood levels of omega-3 fatty acids from fish oil is linked to a lower risk of different cancers, including oral cancer, pharyngeal cancer, esophageal cancer, colon cancer, rectal cancer, breast cancer, ovarian cancer, and prostate cancer. But other research suggests that eating fish does not reduce the risk of cancer.

Pro Omega 3 Intensive Formula is a more convenient source of EPA and DHA than regular marine fish oils for those who would like to supplement their diets with higher amounts of these important omega 3 fatty acids. Our formula contains concentrated marine fish oil, providing enriched levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Plus, it’s lower in saturated fatty acids than regular marine fish oil. For those who don’t eat fish or want to add more omega to their diet, Omega 3 supplements are a convenient way of incorporating these important nutrients into your everyday life. This fish oil supplement is strictly screened for the absence of any toxic metals and chemicals, and is completely free of cholesterol. The oil is carefully processed and handled to avoid oxidation.†

Damage to the kidneys caused the drug cyclosporine. Cyclosporine is a medication that reduces the chance of organ rejection after an organ transplant. Taking fish oil seems to prevent kidney damage in people taking this drug. Fish oil also seems to improve kidney function during the recovery phase following the rejection of a transplanted organ in people taking cyclosporine.