The Lyon Diet Heart Study, performed shortly after the DART study, was a prospective trial of 607 survivors of MI who were randomized to either a Mediterranean diet or a regular Western diet.49 At a mean follow-up of 27 months, the primary end point of death from cardiovascular causes and nonfatal deaths had a 73% relative risk reduction—a positive effect that continued at follow up assessment at a mean of 46 months.50 FA analysis of plasma lipids showed that in the patients randomized to a Mediterranean diet, there was a higher concentration of alpha-linolenic acid as well as EPA. Fish, however, was consumed in similar amounts by both the Western and Mediterranean diet groups. The higher blood level of EPA in the Mediterranean diet arm was attributed to its synthesis from alpha-linolenic acid, which was 60-times higher than the plasma concentration of EPA. In addition, the risk reduction that occurred in this trial could not be attributed to one particular diet intervention because as the consumption of fruits and vegetables increased, the consumption of monounsaturated fat increased, while saturated fat and cholesterol were decreased.
42. Cawood AL, Ding R, Napper FL, Young RH, Williams JA, Ward MJ, Gudmundsen O, Vige R, Payne SP, Ye S, et al. Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. Atherosclerosis. 2010;212:252–9. [PubMed]
In fact, dietary fat intake has been among the most widely studied dietary risk factors for breast and prostate cancers. Two studies from 2002 explain how omega-3 can protect against breast cancer. BRCA1 (breast cancer gene 1) and BRCA2 (breast cancer gene 2) are two tumor suppressor genes that, when functioning normally, help repair DNA damage, a process that also prevents tumor development.

Doses for depression range from less than 1 g/day to 10 g/day, but most studies use doses between 1 and 2 g/day. In my practice, I recommend 1 to 2 g/day of an EPA+DHA combination, with at least 60% EPA, for major depression. I am more cautious in patients with bipolar depression, because the omega-3s may bring on mania, as can most antidepressants. In these individuals, I recommend using omega-3 cautiously, and preferably in combination with a prescription mood stabilizer.
The omega-3 index is also important because it is inversely related to one’s omega-6 to omega-3 ratio — another important measurement (3). A lower omega-6/omega-3 ratio (meaning, you consume a balanced amount of these two fatty acid families) is associated with a reduced risk of many chronic diseases, including cardiovascular disease, cancer, and autoimmune disease, to name a few (4). Of course, most people get far too much omega-6 and too little omega-3, thanks to the plethora of highly processed foods in the Western diet.
Humans are unable to place double bonds beyond position 9 on long chain polyunsaturated fatty acids (FA), making the omega-3 FA synthesized in plants and in marine microalgae essential elements to the human diet.1 Fish contain high levels of 2 omega-3 FA, eicosapentaenoic acid (EPA; C20:5 n-3), and docosahexaenoic acid [DHA]; C22:6 n-3)2,3 (Fig. 1). Many claims about the role of these omega-3 FA have been made in the prevention and treatment of cardiovascular disease. For instance, fish oil is seen as having a therapeutic role in coronary artery disease (CAD), heart failure, fatal and nonfatal arrhythmias, as well as offering an alternative or adjunct to the standard therapy for hypertriglyceridemia and diabetes. This review will highlight the potential mechanisms of fish oil on cardiovascular disease and provide an update of clinical trial results. The established uses in the treatment of hypertriglyceridemia and sources of omega-3 FA—both dietary and drug therapy—will be iterated, along with its potential application in combination with standard hypolipidemic agents. Finally, the limitations of current data will be addressed, as well as suggested recommendations for clinical use.

Stiefel, P., Ruiz-Gutierrez, V., Gajon, E., Acosta, D., Garcia-Donas, M. A., Madrazo, J., Villar, J., and Carneado, J. Sodium transport kinetics, cell membrane lipid composition, neural conduction and metabolic control in type 1 diabetic patients. Changes after a low-dose n-3 fatty acid dietary intervention. Ann Nutr Metab 1999;43(2):113-120. View abstract.
Children require DHA for growth and development, and the brain, CNS and retina rely heavily on the adequate supply of DHA during growth in the womb. Thus women should emphasise DHA in their diets when they become pregnant and continue to take this until they cease breastfeeding. Children continue to need DHA up until the age they start school, so if children under the age of five are taking an omega-3 supplement, it should contain DHA. The exception is for children with developmental problems – where pure EPA or high EPA omega-3 has been shown to be most effective for supporting cognitive function. We would still recommend, where possible, naturally derived sources of omega-3 such as oily fish to support a balanced EPA and DHA intake.
Gerber, J. G., Kitch, D. W., Fichtenbaum, C. J., Zackin, R. A., Charles, S., Hogg, E., Acosta, E. P., Connick, E., Wohl, D., Kojic, E. M., Benson, C. A., and Aberg, J. A. Fish oil and fenofibrate for the treatment of hypertriglyceridemia in HIV-infected subjects on antiretroviral therapy: results of ACTG A5186. J.Acquir.Immune.Defic.Syndr. 4-1-2008;47(4):459-466. View abstract.
Retinol (Vitamin A) B vitamins: Thiamine (B1) Riboflavin (B2) Niacin (B3) Pantothenic acid (B5) Pyridoxine (B6) Biotin (B7) Folic acid (B9) Cyanocobalamin (B12) Ascorbic acid (Vitamin C) Ergocalciferol and Cholecalciferol (Vitamin D) Tocopherol (Vitamin E) Naphthoquinone (Vitamin K) Calcium Choline Chromium Cobalt Copper Fluorine Iodine Iron Magnesium Manganese Molybdenum Phosphorus Potassium Selenium Sodium Sulfur Zinc
Maternal nutrition guidelines have always stressed a diet including sufficient caloric and protein requirements, but recently fatty acids have also been deemed important (17). This is partially due to the fact that EPA and DHA supplementation during pregnancy has been associated with multiple benefits for the infant (Table 1). During pregnancy, the placenta transfers nutrients, including DHA, from the mother to the fetus (18). The amount of omega-3 fatty acid in the fetus is correlated with the amount ingested by the mother, so it is essential that the mother has adequate nutrition (19). The 2010 U.S. Department of Health and Human Services dietary guidelines recommend that women who are pregnant or breastfeeding should “consume 8 to 12 ounces of seafood per week from a variety of seafood types” (12). Ingesting 8–12 oz of seafood per week, depending on the type of fish, is equivalent to ∼300–900 mg EPA+DHA per day. Unfortunately, this amount is not being met by most mothers in the United States and Canada, which means that infants many not be receiving adequate amounts of these vital nutrients in the womb (20).
Results  In total, 1203 participants with omega-3 PUFA treatment (mean age, 43.7 years; mean female proportion, 55.0%; mean omega-3 PUFA dosage, 1605.7 mg/d) and 1037 participants without omega-3 PUFA treatment (mean age, 40.6 years; mean female proportion, 55.0%) showed an association between clinical anxiety symptoms among participants with omega-3 PUFA treatment compared with control arms (Hedges g, 0.374; 95% CI, 0.081-0.666; P = .01). Subgroup analysis showed that the association of treatment with reduced anxiety symptoms was significantly greater in subgroups with specific clinical diagnoses than in subgroups without clinical conditions. The anxiolytic effect of omega-3 PUFAs was significantly better than that of controls only in subgroups with a higher dosage (at least 2000 mg/d) and not in subgroups with a lower dosage (<2000 mg/d).
According to the Cardiovascular Research Institute in Maastricht in Netherlands, “Epidemiological studies show that replacing fat with carbohydrates may even be worse [than the Western-type high-fat diet] and that various polyunsaturated fatty acids (FA) have beneficial rather than detrimental effects on CVD (cardiovascular disease) outcome.” This includes fish-oil fatty acids with anti-inflammatory properties, which can help prevent and reverse a plethora of cardiovascular diseases. (19)
Fish oil supplements came under scrutiny in 2006, when the Food Standards Agency in the UK and the Food Safety Authority of Ireland reported PCB levels that exceeded the European maximum limits in several fish oil brands,[60][61] which required temporary withdrawal of these brands. To address the concern over contaminated fish oil supplements, the International Fish Oil Standards (IFOS) Program, a third-party testing and accreditation program for fish oil products, was created by Nutrasource Diagnostics Inc. in Guelph, Ontario, Canada.[62]
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.
The Japanese notably have the lowest levels of coronary heart disease mortality and atherosclerosis among developed nations — a phenomena that has been largely subscribed to diet. However, even within Japan, a 10-year study of over 41,000 people found that higher intakes of omega-3s were associated with lower risks of nonfatal coronary events (8). A more recent study also found that Japanese with higher omega-3 index levels (10%) had a lower risk of fatal coronary heart disease than those with a lower omega-3 index levels (8%) (9). The study begs the question of whether maybe even the Japanese have room to improve their omega-3 intake and whether 8% should be considered the lower limit of a desirable range.
Five studies with 7 data sets recruited participants without specific clinical conditions.36,47,51,55,60 The main results revealed that there was no significant difference in the association of treatment with reduced anxiety symptoms between patients receiving omega-3 PUFA treatment and those not receiving it (k, 5; Hedges g, –0.008; 95% CI, –0.266 to 0.250; P = .95) (Figure 3A). Fourteen studies with 14 data sets recruited participants with specific clinical diagnoses.33-35,48-50,52-54,56-59,61 The main results revealed a significantly greater association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 14; Hedges g, 0.512; 95% CI, 0.119-0.906; P = .01) (Figure 3A). Furthermore, according to the interaction test, the association of omega-3 PUFA treatment with reduced anxiety symptoms was significantly stronger in subgroups with specific clinical diagnoses than in subgroups without specific clinical conditions (P = .03).
In your final paragraph, you suggest that a ratio of 2:1 EPA/DHA maybe best for reducing inflammation. Are you suggesting using two separate products to obtain that ratio? I can't see how it is achieveable through standard omega-3 products. Good fish oil brands are typically 60% or higher EPA, but never reach a 2:1 ratio in my product searches. According to case studies (link below), 1 gram of EPA per day (60% or more of the total omega-3 content) is sufficient and the highest efficacy.

Meanwhile, blood levels of DHA and EPA are very transitory, reflecting what an individual consumed only recently, while of course prostate cancer has a markedly longer progression. The study was not designed to isolate omega oil :: prostate cancer relationships, so conclusion would be weak. Seems likely to me that when faced with a serious disease, men suddenly begin to try living “right” in a hurry.
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
Fish oil supplements are available as liquids or capsules. Some capsules are enteric-coated to pass through the stomach before dissolving in the small intestine, thus helping prevent indigestion and "fish burps". Poorly manufactured enteric-coated products have the potential to release ingredients too early. ConsumerLab.com, a for-profit supplement testing company, reported that 1 of the 24 enteric-coated fish oil supplements it evaluated released ingredients prematurely.[48]
Recent studies have shown that the consumption of fish oil (or, more specifically, the omega-3 fatty acids found in fish oil) can improve fertility in both men and women. DHA, which is a byproduct of omega-3 fatty acids, plays a key role in the mobility of sperm and health of sperm in men. Low blood levels of DHA have been linked to decreased fertility. Animal studies have found that the DHA in fish is vital to changing dysfunctional round-headed sperm into strong swimmers with cone-shaped heads packed with egg-opening proteins. (29)
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.
There have been numerous clinical trials looking mainly at death, stroke, and cardiac outcomes related to omega 3 consumption, either in food or in supplements. Now the Cochrane Library has published the largest systematic review of these studies to date. Unfortunately, the review shows little benefit from consuming omega 3 fatty acid. This is a fairly extensive review with good statistical power:
Unsafe for children. Fish oil supplements are not considered safe for children. Too much of this fat in their system can lead to a chemical imbalance in the brain which could stunt healthy growth and development. Because of this, and the possible exposure to polychlorinated biphenyls, methylmercury and other toxins which are found in some sources of fish, it is not recommended that women who are pregnant take excessive amounts of fish oil. Servings of fish should be limited to six ounces per week and they should refrain from using fish oil or other fatty acid supplement pills. Children should not consume more than two ounces of fish per week to avoid overexposure to these chemicals. Now you know although fish oil can benefit human beings a lot, fish oil side effects should never be neglected for the sake of your safety. 
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).
The hypotriglyceridemic effect of fish oil is well established and is related to both dose and baseline triglyceride level. Patients with triglycerides <90 mg/dL will be negligibly affected unless very high doses of omega-3 FA are used.67,68 However, in patients with triglycerides >200 mg/dL, who are treated with 4 g/d of fish oil, a 30% reduction in triglycerides is expected.17,69 For patients with triglycerides >500 mg/dL who are at risk for pancreatitis, the National Cholesterol Education Program Adult Treatment Panel III guidelines recommend using fish oil supplements as an adjunctive therapy to fibrates and nicotinic acid.70 Lovaza capsules have been shown to be effective, safe, and comparable to gemfibrozil in treating triglycerides at this range.71,72 The official label recommendation for Lovaza is for patients with triglycerides >500 mg/dL.73
We’ve written about the dose necessary to achieve measurable benefits before. However, a person’s actual omega-3 intake can be tricky to estimate. Even if you eat at least two servings of fatty fish per week, as the American Heart Association recommends (10), your fish might contain more or less omega-3s depending on the fish species, the time of year, and how you cook it. Even taking fish oil supplements isn’t always straightforward, as dose can be impacted by numerous bioavailability factors, as well as genetics, age, gender, medication-use and lifestyle.
After just seven days, those supplementing with krill had their CRP levels reduced by 19.3%, while in the placebo group, CRP levels rose by 15.7%. Even more impressive, the krill benefit was long-lasting. The krill group’s CRP levels continued to fall by 29.7% at 14 days, and 30.9% at 30 days. More importantly from the patients’ points of view, the krill oil supplement reduced pain scores by 28.9%, reduced stiffness by 20.3%, and reduced functional impairment by 22.8%.
If you find yourself in a position where you are just not eating any of these foods, and you want to get enough omega-3 fatty acids, then I think fish oil is okay, but I would limit not the amount of fish oil but the amount listed on the label of EPA and DHA combined. I would limit that amount to around 250 milligrams per day because I don’t think most people need more than that. Some signs that you might not be getting enough omega-3 fatty acids include chronic low-grade inflammation, poor visual acuity, slower mental processing, trouble learning, and possibly Alzheimer’s disease and psychiatric conditions, like depression, anxiety, and attention deficit and hyperactivity disorder, ADHD.
These conversions occur competitively with omega−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. They both utilize the same desaturase and elongase proteins in order to synthesize inflammatory regulatory proteins.[50] The products of both pathways are vital for growth making a balanced diet of omega−3 and omega−6 important to an individual's health.[77] A balanced intake ratio of 1:1 was believed to be ideal in order for proteins to be able to synthesize both pathways sufficiently, but this has been controversial as of recent research.[78]
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.
In fact, dietary fat intake has been among the most widely studied dietary risk factors for breast and prostate cancers. Two studies from 2002 explain how omega-3 can protect against breast cancer. BRCA1 (breast cancer gene 1) and BRCA2 (breast cancer gene 2) are two tumor suppressor genes that, when functioning normally, help repair DNA damage, a process that also prevents tumor development.
Only fish and breast milk contain all the members of the omega-3 family, including its two main stars, EPA and DHA. Because Americans as a rule consume far too few omega-3s from fish or fish oil, it’s no surprise that the majority of Americans have low omega-3 index levels as well. A recent study of global omega-3 index levels found that an estimated 95% of Americans (with the exception of folks from Alaska) had an omega-3 index of 4 or below, putting them in the high risk category (5, 6, 7).
To exclude the possible confounding effects of clinical variables on the Hedges g, metaregression analysis was conducted with an unrestricted maximum likelihood random-effects model of single variables when there were more than 10 data sets available. Specifically, the clinical variables of interest included mean age, female proportion, sample size, mean body mass index, daily omega-3 PUFA dosage, EPA to DHA ratio, treatment duration, dropout rate, and others. In addition, a subgroup meta-analysis was conducted to investigate potential sources of heterogeneity, specifically, a further subgroup meta-analysis focused on those trials that were placebo controlled or non–placebo controlled. To more clearly uncover the differences in the meta-analysis results among the recruited studies, a further subgroup meta-analysis was performed according to the presence of a specific clinical diagnosis or no specific clinical condition, mean omega-3 PUFA daily dosage, and mean age. In addition, in a previous study, the EPA percentage (ie, ≥60%) in the PUFA regimens had different effects on depression treatment.9 Therefore, we also arranged the subgroup meta-analysis based on the EPA percentage. Furthermore, we arranged subgroup meta-analysis procedures only when there were at least 3 data sets included.45 To investigate the potentially different estimated effect sizes between subgroups, we performed an interaction test and calculated the corresponding P values.46
DHA is one of the most prevalent fatty acids in the brain. This could partly explain why our brains do better with a greater supply. A Rush Institute for Healthy Aging study analyzed fish-eating patterns of more than 800 men and women, ages 65 to 94. Those eating fish at least once a week were much less likely to develop Alzheimer's disease than those who turned up their nose at it.
The hypotriglyceridemic effect of fish oil is well established and is related to both dose and baseline triglyceride level. Patients with triglycerides <90 mg/dL will be negligibly affected unless very high doses of omega-3 FA are used.67,68 However, in patients with triglycerides >200 mg/dL, who are treated with 4 g/d of fish oil, a 30% reduction in triglycerides is expected.17,69 For patients with triglycerides >500 mg/dL who are at risk for pancreatitis, the National Cholesterol Education Program Adult Treatment Panel III guidelines recommend using fish oil supplements as an adjunctive therapy to fibrates and nicotinic acid.70 Lovaza capsules have been shown to be effective, safe, and comparable to gemfibrozil in treating triglycerides at this range.71,72 The official label recommendation for Lovaza is for patients with triglycerides >500 mg/dL.73

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]

Foods such as meat, eggs, fish and nuts contain omega-3 and omega-6 fatty acids, which the body converts into endocannabinoids – cannabinoids that the body produces naturally, said Aditi Das, a University of Illinois professor of comparative biosciences and biochemistry, who led the study. Cannabinoids in marijuana and endocannabinoids produced in the body can support the body’s immune system and therefore are attractive targets for the development of anti-inflammatory therapeutics, she said.
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.
Fish and omega-3 fatty acids. If you keep up with the latest nutrition news, you may have a pretty good sense of what they offer. But, if you're like many people, you still can't tell your omega-3s from your omega-6s -- and you sure as heck can't pronounce eicosapentaenoic acid. That's OK. Our fishing expedition turned up some interesting facts to share about omega-3 fatty acids and fish.

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!
My estimate is that close to 90 percent of fish oils on the market today may contain mercury and pesticide residues plus hydrogenated oils. Of course, this is my opinion based on my own research from visiting different manufacturing plants, interviewing companies, and studying the research and the listed ingredients of typical fish oils. I would stay away from ALL fish oils that do not have antioxidants like astaxanthin, which help stabilize the oil from going rancid. I always look for astaxanthin as part of any high-quality fish oil supplement.

First, EPA inhibits the enzyme that produces arachidonic acid. Second, EPA impedes the release of arachidonic acid from cell membranes (where it is stored) and its metabolization once it is released. Without this release and metabolization, your body can’t make eicosanoids. The result is lower risk of the inflammation that would have been caused by all that arachidonic acid going to eicosanoids.
Nielsen, A. A., Jorgensen, L. G., Nielsen, J. N., Eivindson, M., Gronbaek, H., Vind, I., Hougaard, D. M., Skogstrand, K., Jensen, S., Munkholm, P., Brandslund, I., and Hey, H. Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acids. Aliment.Pharmacol.Ther. 2005;22(11-12):1121-1128. View abstract.
×