Krauss-Etschmann et al. (26) Double-blind, placebo-controlled, randomized 311 DHA+EPA daily with either fish oil with DHA (0.5 g) and EPA (0.15 g) or with methyltetrahydrofolic acid (400 μg), both, or placebo, from gestation week 22 Fish-oil supplementation was associated with decreased levels of maternal inflammatory/TH1 cytokines and a decrease of fetal Th2-related cytokines
According to the 2012 National Health Interview Survey, which included a comprehensive survey on the use of complementary health approaches in the United States, fish oil supplements are the nonvitamin/nonmineral natural product most commonly taken by both adults and children. The survey findings indicated that about 7.8 percent of adults (18.8 million) and 1.1 percent of children age 4 to 17 (664,000) had taken a fish oil supplement in the previous 30 days.
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.
Henneicke-von Zepelin, H. H., Mrowietz, U., Farber, L., Bruck-Borchers, K., Schober, C., Huber, J., Lutz, G., Kohnen, R., Christophers, E., and Welzel, D. Highly purified omega-3-polyunsaturated fatty acids for topical treatment of psoriasis. Results of a double-blind, placebo-controlled multicentre study. Br J Dermatol 1993;129(6):713-717. View abstract.

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]

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

Alpha-linolenic Acid (ALA): This plant-based omega-3 is found in green, leafy vegetables, flaxseeds, chia seeds and canola, walnut and soybean oils (although those rancid oils are not ones I generally recommend). ALA is known as a short-chain omega-3, meaning your body has to convert it into longer-chained EPA and DHA to synthesize it. This process is rather inefficient and only about one percent of the ALA you consume is converted to the long-chain version your body needs (although this percentage is slightly higher for women).
When taking fish oil, more is not always better. Remember that you want it to stay in a balanced ratio with omega-6 fats. For most people, I recommend a 1,000-milligram dose of fish oil daily as a good amount and the most scientifically studied dosage. I highly recommend not taking more than that unless directed to under the supervision of a doctor.
In a U.K. study, children of mothers who ate more than 12 ounces a week actually scored better on tests of verbal I.Q., social behavior, and development and communication than children of mothers who ate none. In the Seychelles Islands, where people average 12 fish meals -- not ounces -- a week, there are no reports of links between mercury exposure and poor outcomes in children. These studies suggest that eating less than 12 ounces of fish each week could do more harm to a child's developing neurological system than mercury poisoning.
Three omega−3 fatty acids are important in human physiology, α-linolenic acid (18:3, n-3; ALA), eicosapentaenoic acid (20:5, n-3; EPA), and docosahexaenoic acid (22:6, n-3; DHA).[67] These three polyunsaturates have either 3, 5, or 6 double bonds in a carbon chain of 18, 20, or 22 carbon atoms, respectively. As with most naturally-produced fatty acids, all double bonds are in the cis-configuration, in other words, the two hydrogen atoms are on the same side of the double bond; and the double bonds are interrupted by methylene bridges (-CH
There is also evidence that mothers who use EPA and DHA supplementation during pregnancy and breastfeeding may protect their children against allergies. This may be due to the fact that fish-oil supplementation has been associated with decreased levels of body cells associated with inflammation and immune response (26). In a study about food allergy and IgE-associated eczema, the period prevalence of food allergy was lower in the maternal EPA+DHA supplementation group compared to placebo (P < 0.05), and the incidence of IgE-associated eczema was also lower in the maternal EPA+DHA supplementation group compared to placebo (P < 0.05) (27).
In some cases, fish oil pills may cause loose stools, nausea, diarrhea, and decreased appetite, fat in the stools, vomiting or constipation. These side effects can be minimized by taking a fish oil capsule that is coated, which is designed to help eliminate the "fish burps" many users complain about. Starting with low doses of the supplement and working up to a full dose can also help minimize side effects. You can also pair fish oil supplements with meals so that they enter your body more slowly, minimizing the risk of side effects occurring.
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).
The National Institutes of Health (NIH) has created a website, NIH Clinical Research Trials and You, to help people learn about clinical trials, why they matter, and how to participate. The site includes questions and answers about clinical trials, guidance on how to find clinical trials through and other resources, and stories about the personal experiences of clinical trial participants. Clinical trials are necessary to find better ways to prevent, diagnose, and treat diseases.
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).
Several large studies have linked higher blood levels of long-chain omega-3s with higher risks of prostate cancer. However, other research has shown that men who frequently eat seafood have lower prostate cancer death rates and that dietary intakes of long-chain omega-3s aren’t associated with prostate cancer risk. The reason for these apparently conflicting findings is unclear. 

Like I mentioned earlier, there are no official guidelines for the proper amount of omega-3s you should consume each day. However, most organization agree that at least 2 servings of a 3.5 ounce serving of fish (preferably oily) each week is a good start. That equals about 500 milligrams of EPA/DHA each day. For treating disease, up to 4,000 milligrams per day is recommended by various studies, although values do vary. (96) It’s why a pescatarian diet can have such health protective effects.

Increasing ALA intake probably makes little or no difference to all‐cause mortality (RR 1.01, 95% CI 0.84 to 1.20, 19,327 participants; 459 deaths, 5 RCTs),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25, 18,619 participants; 219 cardiovascular deaths, 4 RCTs), and it may make little or no difference to CHD events (RR 1.00, 95% CI 0.80 to 1.22, 19,061 participants, 397 CHD events, 4 RCTs, low‐quality evidence). However, increased ALA may slightly reduce risk of cardiovascular events (from 4.8% to 4.7%, RR 0.95, 95% CI 0.83 to 1.07, 19,327 participants; 884 CVD events, 5 RCTs, low‐quality evidence), and probably reduces risk of CHD mortality (1.1% to 1.0%, RR 0.95, 95% CI 0.72 to 1.26, 18,353 participants; 193 CHD deaths, 3 RCTs), and arrhythmia (3.3% to 2.6%, RR 0.79, 95% CI 0.57 to 1.10, 4,837 participants; 141 events, 1 RCT). Effects on stroke are unclear.

When taking fish oil, more is not always better. Remember that you want it to stay in a balanced ratio with omega-6 fats. For most people, I recommend a 1,000-milligram dose of fish oil daily as a good amount and the most scientifically studied dosage. I highly recommend not taking more than that unless directed to under the supervision of a doctor.

The reason why fish oil could increase a man’s risk of prostate cancer is IMBALANCE. Like I said earlier, omega-6 fatty acids aren’t bad for you. In fact, if your diet contains too many omega-3 fatty acids, your immune system wouldn’t work very well because omega-3 and omega-6 fatty acids are meant to work in a system of checks and balances. Omega-3 fatty acids suppress inflammation, and omega-6 fatty acids promote inflammation, which actually supports your body’s natural system of defense like activating your white blood cells.

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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.
Because patients with depression experience rapid shrinking of their hippocampus, many strategies for relieving depression focus on increasing new brain cell growth in that specific area of the brain.23 There’s now evidence that increasing omega-3 intake, especially DHA, may be an effective way of treating or preventing depression, partly by protecting the hippocampus from further shrinkage.23
For slowing weight loss in patients with cancer: 30 mL of a specific fish oil product (ACO Omega-3, Pharmacia, Stockholm, Sweden) providing 4.9 grams of EPA and 3.2 grams of DHA daily for 4 weeks has been used. 7.5 grams of fish oil daily providing EPA 4.7 grams and DHA 2.8 grams has been used for about 6 weeks. In addition, two cans of a fish oil nutritional supplement containing 1.09 grams of EPA and 0.96 grams of DHA per can have been used daily for up to 7 weeks.
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.)
4. Omega-3 has been found to save the lives of children going through short bowel syndrome (SBS), which is uncommon but impacts thousands of people in the United States. SBS can occur from birth (when a portion of the intestine fails to develop) or due to an infectious inflammatory disease striking premature newborns. In adults, it can be caused by surgery for Crohn's disease or injury.
In my opinion, the key benefit of DHA lies in its unique spatial characteristics. As mentioned earlier, the extra double bond (six in DHA vs. five in EPA) and increased carbon length (22 carbons in DHA vs. 20 in EPA) means that DHA takes up takes up a lot more space than does EPA in the membrane. Although this increase in spatial volume makes DHA a poor substrate for phospholipase A2 as well as the COX and LOX enzymes, it does a great job of making membranes (especially those in the brain) a lot more fluid as the DHA sweeps out a much greater volume in the membrane than does EPA. This increase in membrane fluidity is critical for synaptic vesicles and the retina of the eye as it allows receptors to rotate more effectively thus increasing the transmission of signals from the surface of the membrane to the interior of the nerve cells. This is why DHA is a critical component of these highly fluid portions of the nerves (7). On the other hand, the myelin membrane is essentially an insulator so that relatively little DHA is found in that part of the membrane.

Children, in particular, seem to experience problems with sleep when they don’t get enough omega-3 fatty acids in their diets. In adults, low omega-3 levels are associated with obstructive sleep apnea. One reason for this may be that low omega-3s are linked to lower levels of melatonin, the hormone partly responsible for helping you to get to sleep in the first place.
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.

A tremendous body of research has been conducted on these important nutrients since it was first discovered in the 1950s that fish oil offered many health benefits and that these benefits were attributable to a type of polyunsaturated fat called omega-3. Despite the volumes of research on omega-3s, it is only in recent years (within the last 15 years or so) that the actions of EPA and DHA have come to be understood individually. Researchers now often investigate the actions of EPA and DHA individually rather than together, no longer simply under the generic label omega-3 as they are widely referred to.
All people need to consume omega-3 fats regularly. The recommended daily intake for adults is 1.6 grams for males  and 1.1 grams for females, according to the National Institutes of Health. The omega-3 family encompasses numerous fatty acids, but three primary forms are eicosapentaenoic acid, docosahexaenoic acid, and alpha-linolenic acid. The first two forms primarily occur in fish, such as salmon, mackerel, and tuna. The third can be found in plant oils, including flaxseed, soybean, walnut, and canola oils.
A 2012 study involved children from 6 to 12 years of age with ADHD who were being treated with methylphenidate and standard behavior therapy for more than six months. The parents of these children reported no improvement in behavior and academic learning using these standard treatments. The researchers randomly gave some of the children an omega-3 and omega-6 acid supplementation or a placebo. They found “statistically significant improvement” for the omega group in the following categories: restlessness, aggressiveness, completing work and academic performance. (5)
The question is whether the observed cardiovascular benefits often found among fish eaters is due solely to the oils in fish or to some other characteristics of seafood or to still other factors common to those who eat lots of fish, like eating less meat or pursuing a healthier lifestyle over all. Whatever the answer, it does not seem to be fish oil supplements.
Fearon, K. C., Von Meyenfeldt, M. F., Moses, A. G., Van Geenen, R., Roy, A., Gouma, D. J., Giacosa, A., Van Gossum, A., Bauer, J., Barber, M. D., Aaronson, N. K., Voss, A. C., and Tisdale, M. J. Effect of a protein and energy dense n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut 2003;52(10):1479-1486. View abstract.

There have been conflicting results reported about EPA and DHA and their use with regard to major coronary events and their use after myocardial infarction. EPA+DHA has been associated with a reduced risk of recurrent coronary artery events and sudden cardiac death after an acute myocardial infarction (RR, 0.47; 95% CI: 0.219–0.995) and a reduction in heart failure events (adjusted HR: 0.92; 99% CI: 0.849–0.999) (34–36). A study using EPA supplementation in combination with a statin, compared with statin therapy alone, found that, after 5 y, the patients in the EPA group (n = 262) who had a history of coronary artery disease had a 19% relative reduction in major coronary events (P = 0.011). However, in patients with no history of coronary artery disease (n = 104), major coronary events were reduced by 18%, but this finding was not significant (37). This Japanese population already has a high relative intake of fish compared with other nations, and, thus, these data suggest that supplementation has cardiovascular benefits in those who already have sufficient baseline EPA+DHA levels. Another study compared patients with impaired glucose metabolism (n = 4565) with normoglycemic patients (n = 14,080). Impaired glucose metabolism patients had a significantly higher coronary artery disease HR (1.71 in the non-EPA group and 1.63 in the EPA group). The primary endpoint was any major coronary event including sudden cardiac death, myocardial infarction, and other nonfatal events. Treatment of impaired glucose metabolism patients with EPA showed a significantly lower major coronary event HR of 0.78 compared with the non–EPA-treated impaired glucose metabolism patients (95% CI: 0.60–0.998; P = 0.048), which demonstrates that EPA significantly suppresses major coronary events (38). When looking at the use of EPA+DHA and cardiovascular events after myocardial infarction, of 4837 patients, a major cardiovascular event occurred in 671 patients (13.9%) (39). A post hoc analysis of the data from these diabetic patients showed that rates of fatal coronary heart disease and arrhythmia-related events were lower among patients in the EPA+DHA group than among the placebo group (HR for fatal coronary heart disease: 0.51; 95% CI: 0.27–0.97; HR for arrhythmia-related events: 0.51; 95% CI: 0.24–1.11, not statistically significant) (39). Another study found that there was no significant difference in sudden cardiac death or total mortality between an EPA+DHA supplementation group and a control group in those patients treated after myocardial infarction (40). Although these last 2 studies appear to be negative in their results, it is possible that the more aggressive treatment with medications in these more recent studies could attribute to this.
Reduce Metabolic Syndrome Symptoms: The cluster of risk factors known as metabolic syndrome includes abdominal obesity, high blood sugar, high triglycerides, high blood pressure and low HDL cholesterol. These risk factors are indicative of a high chance you might develop heart disease, stroke or diabetes. Multiple studies have found omega-3 supplementation improve the symptoms of metabolic syndrome and may help to protect you from the related diseases. (22, 23, 24, 25)
Science is dynamic, not static, and as scientific understanding advances scientists sometimes have to modify their positions. Dr. Kidd’s position on EPA and DHA has now changed due to advances in the clinical and basic scientific research. Though the brain carries predominantly DHA and very little EPA, clinical trial results clearly indicate EPA has benefit for mood and probably other higher brain functions. At the basic science level, it has become clear that both EPA and DHA, not DHA alone, are required for the brain to make new nerve cells. Dr. Kidd very closely monitors the research on EPA and… Read more »

Heart disease. Research suggests that 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.
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:
Sangiovanni, J. P., Agron, E., Meleth, A. D., Reed, G. F., Sperduto, R. D., Clemons, T. E., and Chew, E. Y. {omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study. Am J Clin Nutr 2009;90(6):1601-1607. View abstract.
Mercury and polychlorinated biphenyls (PCBs) are common toxins in seafood. Although the U.S. banned the use of PCBs and DDT in 1976, these and other chemicals are still used in half the world's commercial chemical processes. Substances like these can hang around in the air, soil, and water for many years. They end up in the bodies of fish and animals.
The question is whether the observed cardiovascular benefits often found among fish eaters is due solely to the oils in fish or to some other characteristics of seafood or to still other factors common to those who eat lots of fish, like eating less meat or pursuing a healthier lifestyle over all. Whatever the answer, it does not seem to be fish oil supplements.
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.