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.
Fish oil’s most potent effect on atherosclerosis may be related to its potential to alter plaque inflammation, thereby stabilizing vulnerable plaques. In recent years there has been a growing body of evidence that is shifting the paradigm of how inflammation is contained and dissipated.4 In this new model, inflammation resolution is an active process mediated by lipid-derived compounds. Newly discovered families of chemical mediators, resolvins, and protectins5,6 are directly involved in blocking neutrophil migration, infiltration, and recruitment, as well as in blocking T-cell migration and promoting T-cell apoptosis.7–12 In addition, protectins can reduce tumor necrosis factor and interferon secretion.13 Interestingly, both protectins and resolvins are strictly derived from omega-3 FA. EPA is the substrate of the resolvins family and DHA can be converted to both resolvins and protectins.7 It may be that the effects of fish oil on inflammatory mediators underlie the positive findings demonstrated in several trials assessing fish oil and plaque stability.14–16
The Federal Government’s Dietary Guidelines for Americans 2015–2020 recommends that adults eat 8 or more ounces of a variety of seafood (fish or shellfish) per week for the total package of nutrients seafood provides, and that some seafood choices with higher amounts of EPA and DHA be included. Smaller amounts of seafood are recommended for young children.
First difference is in the area of omega-6 fatty acid metabolism. Whereas EPA is the inhibitor of the enzyme (D5D) that directly produces AA, DHA is an inhibitor of another key enzyme delta-6-desaturase (D6D) that produces the first metabolite from linoleic acid known as gamma linolenic acid or GLA (6). However, this is not exactly an advantage. Even though reduction of GLA will eventually decrease AA production, it also has the more immediate effect of reducing the production of the next metabolite known as dihomo gamma linolenic acid or DGLA. This can be a disaster as a great number of powerful anti-inflammatory eicosanoids are derived from DGLA. This is why if you use high-dose DHA it is essential to add back trace amounts of GLA to maintain sufficient levels of DGLA to continue to produce anti-inflammatory eicosanoids.
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]
“This systematic review did find moderate evidence that ALA, found in plant oils (such as rapeseed or canola oil) and nuts (particularly walnuts) may be slightly protective of some diseases of the heart and circulation. However, the effect is very small, 143 people would need to increase their ALA intake to prevent one person developing arrhythmia. One thousand people would need to increase their ALA intake to prevent one person dying of coronary heart disease or experiencing a cardiovascular event.  ALA is an essential fatty acid, an important part of a balanced diet, and increasing intakes may be slightly beneficial for prevention or treatment of cardiovascular disease."
A number of trials have found that omega-3 PUFAs might reduce anxiety under serious stressful situations. Case-controlled studies have shown low peripheral omega-3 PUFA levels in patients with anxiety disorders.27-31 A cohort study found that high serum EPA levels were associated with protection against posttraumatic stress disorder.32 In studies of therapeutic interventions, while a randomized clinical trial of adjunctive EPA treatment in patients with obsessive-compulsive disorder revealed that EPA augmentation had no beneficial effect on symptoms of anxiety, depression, or obsessive-compulsiveness,33 a randomized clinical trial involving participants with substance abuse showed that EPA and DHA administration was accompanied by significant decreases in anger and anxiety scores compared with placebo.34 In addition, a randomized clinical trial found that omega-3 PUFAs had additional effects on decreasing depressive and anxiety symptoms in patients with acute myocardial infarction,35 and a randomized clinical trial demonstrated that omega-3 PUFAs could reduce inflammation and anxiety among healthy young adults facing a stressful major examination.36 Despite the largely positive findings of these trials, the clinical application of the findings is unfortunately limited by their small sample sizes.

Another study conducted by researchers at Rhode Island Hospital examined the relationship between fish oil supplementation and indicators of cognitive decline. The subjects of the study were older adults: 229 cognitively normal individuals, 397 patients with mild cognitive impairment and 193 patients with Alzheimer’s disease. They were assessed with neuropsychological tests and brain magnetic resonance imaging every six months while taking fish oil supplements. The study found that the adults taking fish oil (who had not yet developed Alzheimer’s and did not have genetic risk factor for developing Alzheimer’s known as APOE ε4) experienced significantly less cognitive decline and brain shrinkage than adults not taking fish oil. (9)

Saito, Y., Yokoyama, M., Origasa, H., Matsuzaki, M., Matsuzawa, Y., Ishikawa, Y., Oikawa, S., Sasaki, J., Hishida, H., Itakura, H., Kita, T., Kitabatake, A., Nakaya, N., Sakata, T., Shimada, K., and Shirato, K. 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(1):135-140. View abstract.

Before getting to know some of the fish oil side effects, you have to know more about fish oil, like its benefits and usages. Fish oil has become a popular supplement for athletes, as well as those looking to improve their overall health. Many claims have been made regarding the improvements to the body which can be made by using fish oil to increase the body's level of fatty omega-3 acids. Some of these claims have been backed up by studies, while others have not been proven with significant scientific evidence. There are also some precautions that need to be addressed if you will be taking fish oil regularly. People with certain health conditions may see a worsening of their symptoms if they increase their intake of fatty acids too quickly or with the wrong products.
In fact, fish oil is even dipping its way into mainstream medicine. In September 2018, Amarin Corporation, the biopharmaceutical developer of pharmaceutical-grade fish oil Vascepa, released preliminary findings of its double-blind clinical trial. In the study, researchers tracked more than 8,000 adults for a median 4.9 years. The mix of study participants had either established cardiovascular disease or type 2 diabetes and another cardiovascular disease risk factor, along with persistently elevated triglycerides.

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

Heavy metal poisoning by the body's accumulation of traces of heavy metals, in particular mercury, lead, nickel, arsenic, and cadmium, is a possible risk from consuming fish oil supplements.[medical citation needed] Also, other contaminants (PCBs, furans, dioxins, and PBDEs) might be found, especially in less-refined fish oil supplements.[citation needed] However, heavy metal toxicity from consuming fish oil supplements is highly unlikely, because heavy metals selectively bind with protein in the fish flesh rather than accumulate in the oil. An independent test in 2005 of 44 fish oils on the US market found all of the products passed safety standards for potential contaminants.[107][unreliable source?]

Maclean, C. H., Mojica, W. A., Morton, S. C., Pencharz, J., Hasenfeld, Garland R., Tu, W., Newberry, S. J., Jungvig, L. K., Grossman, J., Khanna, P., Rhodes, S., and Shekelle, P. Effects of omega-3 fatty acids on lipids and glycemic control in type II diabetes and the metabolic syndrome and on inflammatory bowel disease, rheumatoid arthritis, renal disease, systemic lupus erythematosus, and osteoporosis. Evid.Rep.Technol.Assess.(Summ.) 2004;(89):1-4. View abstract.

The biggest cause of omega-3 deficiency is the overconsumption of foods high in omega-6 fatty acids. Omega-6 comes from things like fried foods, fast foods and boxed foods that contain vegetables oils like soybean oil, canola oil, sunflower oil, cottonseed oil and corn oil. When you consume too much omega-6, it can decrease your body’s ability to metabolize healthy omega-3 fatty acids. (36)
In addition, there was no significant difference in the association of treatment with reduced anxiety symptoms between participants receiving omega-3 PUFAs and those not receiving omega-3 PUFAs in the adolescent subgroup (aged <18 years) (k, 3; Hedges g, 0.020; 95% CI, –0.209 to 0.250; P = .86),48,53,57 in the adult subgroup (aged ≥18 years but <60 years) (k, 11; Hedges g, 0.388; 95% CI, –0.012 to 0.788; P = .06),33,35,36,47,49-51,54-56,59 or in the elderly subgroup (aged ≥60 years) (k, 3; Hedges g, –0.112; 95% CI, –0.406 to 0.181; P = .45).52,58,60 These insignificant results might be due to the smaller sample sizes in each subgroup.

These low levels are especially bad when compared to the numbers from the Japanese population. In Japan, the average omega-3 index level is more than double that of the average American, with some surveys showing Japanese men consume over 100 g (approximately 3.5 oz) of fish every day. These radically different dietary habits help explain how even those with omega-3 indexes in the lowest 5th percentile of the Japanese population have higher omega-3 index averages than most Americans (8).

I have been a long time user of Fish Oils for their anti-inflammatory action, unfortunately I have not really obtained much benefit in that area, though the benefits of eye health have been very good. I have been thinking of dropping this supplement for a number of reasons, first, I read a while back the possibility of “sudden death” in those that supplement in larger quantities, I use 1-2 tablespoons since I have an autoimmune issue. Now that you have brought forth the information that Fish Oil suppresses CD8+ counts I will definitely do so, reason being CD8+ T cells are very much at the forefront of containing the Epstein Barr virus and this virus has been implicated in most autoimmune issues. I doubt it will make a difference with my AI, but perhaps it will help prevent other issues down the line. Keep up the great work, very informative!
The ultimate goal of using omega-3 fatty acids is the reduction of cellular inflammation. Since eicosanoids derived from arachidonic acid (AA), an omega-6 fatty acid, are the primary mediators of cellular inflammation, EPA becomes the most important of the omega-3 fatty acids to reduce cellular inflammation for a number of reasons. First, EPA is an inhibitor of the enzyme delta-5-desaturase (D5D) that produces AA (1). The more EPA you have in the diet, the less AA you produce. This essentially chokes off the supply of AA necessary for the production of pro-inflammatory eicosanoids (prostaglandins, thromboxanes, leukotrienes, etc.). DHA is not an inhibitor of this enzyme because it can’t fit into the active catalytic site of the enzyme due to its larger spatial size. As an additional insurance policy, EPA also competes with AA for the enzyme phospholipase A2 necessary to release AA from the membrane phospholipids (where it is stored). Inhibition of this enzyme is the mechanism of action used by corticosteroids. If you have adequate levels of EPA to compete with AA (i.e. a low AA/EPA ratio), you can realize many of the benefits of corticosteroids but without their side effects. That’s because if you don’t release AA from the cell membrane then you can’t make inflammatory eicosanoids. Because of its increased spatial dimensions, DHA is not a good competitor of phospholipase A2 relative to EPA. On the other hand, EPA and AA are very similar spatially so they are in constant competition for the phospholipase A2 enzyme just as both fatty acids are in constant competition for the delta-5 desaturase enzyme. This is why measuring the AA/EPA ratio is such a powerful predictor of the state of cellular inflammation in your body.
If you get your omega-3 index measured, you’ll know if your current efforts are sufficient. And this knowledge is especially important given that even health-conscious people are not always self-aware. One survey found that in a group of people with omega-3 index levels in the intermediate risk range, some 30% believed they were consuming enough omega-3s (11). One registered dietitian wrote a compelling story about exactly this experience. She discovered she was in the intermediate range, in spite of her intentions to eat enough fish.
A Pregnancy Prerequisite: Omega-3 fatty acids directly affect brain development, making it crucial for expectant mothers. Additionally, research indicates they decrease a mother's risk of depression. When the mother doesn't have enough of these essential fatty acids, the baby borrows from her. Some prenatal vitamins now include omega-3s, so be sure to check the label or grab a handful of walnuts each day.
There was no significant association between the Hedges g and mean age (k, 17; P = .51), female proportion (k, 18; P = .32), mean omega-3 PUFA dosage (k, 19; P = .307), EPA to DHA ratio (k, 17; P = .86), dropout rate in the omega-3 PUFA group (k, 18; P = .71), duration of omega-3 PUFA treatment (k, 19; P = .14), Jadad score of randomization (k, 19; P = .10), Jadad score of blindness (k, 19; P = .57), or total Jadad score (k, 19; P = .18).
DHA is vital for early brain development and maintenance, while EPA seems to be closely related to behavior and mood. Together, both molecules provide critical neuroprotective benefits.11 These neuroprotective effects are important for the prevention of age-related brain shrinkage (cortical atrophy). Aging adults with brain shrinkage often experience memory loss, cognitive decline, and an increase in depression.12-14
In the United States, the Institute of Medicine publishes a system of Dietary Reference Intakes, which includes Recommended Dietary Allowances (RDAs) for individual nutrients, and Acceptable Macronutrient Distribution Ranges (AMDRs) for certain groups of nutrients, such as fats. When there is insufficient evidence to determine an RDA, the institute may publish an Adequate Intake (AI) instead, which has a similar meaning, but is less certain. The AI for α-linolenic acid is 1.6 grams/day for men and 1.1 grams/day for women, while the AMDR is 0.6% to 1.2% of total energy. Because the physiological potency of EPA and DHA is much greater than that of ALA, it is not possible to estimate one AMDR for all omega−3 fatty acids. Approximately 10 percent of the AMDR can be consumed as EPA and/or DHA.[105] The Institute of Medicine has not established a RDA or AI for EPA, DHA or the combination, so there is no Daily Value (DVs are derived from RDAs), no labeling of foods or supplements as providing a DV percentage of these fatty acids per serving, and no labeling a food or supplement as an excellent source, or "High in..."[citation needed] As for safety, there was insufficient evidence as of 2005 to set an upper tolerable limit for omega−3 fatty acids,[105] although the FDA has advised that adults can safely consume up to a total of 3 grams per day of combined DHA and EPA, with no more than 2 g from dietary supplements.[8]
More than 30 clinical trials have tested different omega-3 preparations in people with depression. Most studies have used omega-3s as add-on therapy for people who are taking prescription antidepressants with limited or no benefit. Fewer studies have examined omega-3 therapy alone. Clinical trials typically use EPA alone or a combination of EPA plus DHA, at doses from 0.5 to 1 gram per day to 6 to 10 grams per day. To give some perspective, 1 gram per day would correspond to eating three salmon meals per week.
Eicosatetraenoic Acid (ETA): ETA is a lesser-known omega-3 fatty acid that also contains 20 carbons, like EPA, but only four bonds instead of five. It is found richly inroe oil and green-lipped mussel and is only recently being recognized for its potent health benefits. Not only is it anti-inflammatory, like the other omega-3s, but ETA can also limit your body’s production of the inflammatory omega-6 fatty acid arachidonic acid (ARA). In fact, ETA redirects the enzyme that normally creates ARA to convert it to EPA instead!
• Fish oil – Fish oil is among the primary ways that people enhance their intake of omega-3 fats. High-quality fish oils can certainly provide many health benefits. However, this oil is weak in antioxidants. This means that as you increase your omega-3 intake through fish oil consumption, you actually increase your need for added antioxidant protection.
Infant development. There is some evidence that mothers who eat fish or take fish oil supplements during pregnancy may improve some aspects of their baby's mental development. Taking fish oil during breast-feeding does not have this effect. However, feeding infants formula fortified with fish oil appears to improve some aspect of the baby's vision by the age of 2 months.