Chemical structure of alpha-linolenic acid (ALA), an essential omega−3 fatty acid, (18:3Δ9c,12c,15c, which means a chain of 18 carbons with 3 double bonds on carbons numbered 9, 12, and 15). Although chemists count from the carbonyl carbon (blue numbering), biologists count from the n (ω) carbon (red numbering). Note that, from the n end (diagram right), the first double bond appears as the third carbon-carbon bond (line segment), hence the name "n-3". This is explained by the fact that the n end is almost never changed during physiological transformations in the human body, as it is more energy-stable, and other compounds can be synthesized from the other carbonyl end, for example in glycerides, or from double bonds in the middle of the chain.

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!
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.
Jump up ^ Siscovick DS, Barringer TA, Fretts AM, Wu JH, Lichtenstein AH, Costello RB, Kris-Etherton PM, Jacobson TA, Engler MB, Alger HM, Appel LJ, Mozaffarian D (2017). "Omega−3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association". Circulation. 135 (15): e867–84. doi:10.1161/CIR.0000000000000482. PMID 28289069.
Omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential nutrients that have potential preventive and therapeutic effects on psychiatric disorders, such as anxiety and depression,7-15 as well as comorbid depression and anxiety in physically ill patients,16-19 patients with coronary heart disease,20,21 and pregnant women.22,23 Preclinical data support the effectiveness of omega-3 PUFAs as treatment for anxiety disorders. Song et al24,25 found that an EPA-rich diet could reduce the development of anxiety-like behaviors in rats as well as normalize dopamine levels in the ventral striatum. In addition, Yamada et al26 showed that a high dietary omega-3 to omega-6 PUFA ratio reduced contextual fear behaviors in mice and that these effects were abolished by a cannabinoid CB1 receptor antagonist.
Fish oils rich in omega 3 fatty acids help improve fertility and cell division. Preliminary research conducted on animals has shown that when males are fed a diet containing fish oil, the quality of the sperm is enhanced. After ejaculation, the sperm has increased survival against lipid peroxidative attacks in the female genital tract, thereby increasing the chances of conception. On the other hand, similar animal studies have shown inhibition in the synthesis of prostaglandin E and prostaglandin F, which are produced in large quantities by human seminal vesicles. The research, however, found no impact on the count and mobility of sperm.
CONDITIONS OF USE AND IMPORTANT INFORMATION: This information is meant to supplement, not replace advice from your doctor or healthcare provider and is not meant to cover all possible uses, precautions, interactions or adverse effects. This information may not fit your specific health circumstances. Never delay or disregard seeking professional medical advice from your doctor or other qualified health care provider because of something you have read on WebMD. You should always speak with your doctor or health care professional before you start, stop, or change any prescribed part of your health care plan or treatment and to determine what course of therapy is right for you.
Several small studies have shown that combination therapy with fish oil and HMG CoA reductase inhibitors is safe.56–61 The largest trial to date, the JELIS trial,32 was an open label trial of 18,645 Japanese adults with hypercholesterolemia who were randomized to a standard statin regimen or a fish oil formulation containing 1.8 g of EPA added to a statin medication. The cohort was made up mostly of postmenopausal, nonobese women with a 15% to 20% incidence of diabetes, tobacco use, or CAD. The primary outcome of any major cardiovascular event, at a mean of 4.6 years, was moderately reduced by a relative risk reduction of 26%. Both unstable angina and nonfatal MI were reduced, but no change was seen in sudden death. Overall, the findings were remarkable because at baseline approximately 90% of Japanese consumed at least 900 mg of EPA and DHA per day.62 The rates of cancer, joint pain, lumbar pain, or muscle pain were similar in the 2 groups. There was a similar rate of increase in measures of creatine phosphokinase, but more patients had an increase in aspartate aminotransferase levels (0.6% vs. 0.4%) in the fish oil group. The rate of bleeding was 1.1% in the fish oil combination group versus 0.6% in the HMG–CoA reductase inhibitor group.
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.
Fish oil is also extremely beneficial for pregnant women and their children. Throughout pregnancy and also while breastfeeding, a woman’s omega-3 needs are even higher than usual. According to the American Pregnancy Association, most U.S. women are deficient in EPA and especially DHA going into pregnancy and get even more depleted during pregnancy, as the placenta supplies the fetus with DHA from the mother’s tissue. Omega-3 DHA is a critical building block of the fetal brain, eyes and nervous system. Once the baby is born, omega-3s continue to be vital to healthy brain development and immune function. (30)
Matsumura  K, Noguchi  H, Nishi  D, Hamazaki  K, Hamazaki  T, Matsuoka  YJ.  Effects of omega-3 polyunsaturated fatty acids on psychophysiological symptoms of post-traumatic stress disorder in accident survivors: a randomized, double-blind, placebo-controlled trial.  J Affect Disord. 2017;224:27-31. doi:10.1016/j.jad.2016.05.054PubMedGoogle ScholarCrossref

It is believed that regular consumption of fish oil aids in boosting your immune system, thereby enabling you to resist the occurrence of common diseases like colds, cough, and the flu. Omega-3 fatty acids present in fish oil bolster the immune system by affecting the activity and amount of cytokines and eicosanoids present in our body. Researchers have also studied the effect of a fish meal and fish oil on the immune system of pigs and found that fish oil aided in the growth of the animals. Similar research conducted on mice at Taichung Veterans General Hospital, Taiwan, also gave positive results.
The systematic review suggests that eating more ALA through food or supplements probably has little or no effect on cardiovascular deaths or deaths from any cause. However, eating more ALA probably reduces the risk of heart irregularities from 3.3 to 2.6%. The review team found that reductions in cardiovascular events with ALA were so small that about 1000 people would need to increase consumption of ALA for one of them to benefit. Similar results were found for cardiovascular death. They did not find enough data from the studies to be able to measure the risk of bleeding or blood clots from using ALA.

Evidence linking fish oil and cancer has been all over the map. Some research suggests diets high in fatty fish or fish oil supplements might reduce the risk of certain cancers, including prostate cancer. Other research shows just the opposite, a  link between eating a lot of oily fish or taking potent fish oil supplements and a 43% increased risk for prostate cancer overall, and a 71% increased risk for aggressive prostate cancer.
So for those people who will not eat liver, cod liver oil on a daily basis can be a very good way of getting that. And you do benefit from the omega-3 fatty acids, and with the cod liver oil, it may even be unimportant to eat fish if you’re getting the cod liver oil, although it’s still better to focus on the fish, the egg yolks, and just add some of the cod liver oil.

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.)


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.

Omega 3 fatty acids—found in supplements and naturally in some foods like certain fish, and nuts and seeds—have long been touted for their health benefits, especially heart health. Yet, a lot is still unknown, including whether it's better to get your omega 3 fats from pills or in food—and the debate continues regarding how much they may actually help you avoid heart disease.


We included 79 RCTs (112,059 participants) in this review update and found that 25 were at low summary risk of bias. Trials were of 12 to 72 months’ duration and included adults at varying cardiovascular risk, mainly in high‐income countries. Most studies assessed LCn3 supplementation with capsules, but some used LCn3‐ or ALA‐rich or enriched foods or dietary advice compared to placebo or usual diet.
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.
^ Jump up to: a b Casula M, Soranna D, Catapano AL, Corrao G (August 2013). "Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: A meta-analysis of randomized, placebo controlled trials [corrected]". Atherosclerosis. Supplements. 14 (2): 243–51. doi:10.1016/S1567-5688(13)70005-9. PMID 23958480.
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

Arsenault, L. N., Matthan, N., Scott, T. M., Dallal, G., Lichtenstein, A. H., Folstein, M. F., Rosenberg, I., and Tucker, K. L. Validity of estimated dietary eicosapentaenoic acid and docosahexaenoic acid intakes determined by interviewer-administered food frequency questionnaire among older adults with mild-to-moderate cognitive impairment or dementia. Am J Epidemiol 7-1-2009;170(1):95-103. View abstract.


It is also believed that women who do not have a sufficient intake of EPA and DHA in their diet suffer from depression after childbirth, as there is a transfer of some amount of brain mass from the mother to the child in the last stages of pregnancy. Thus, it is very beneficial to consume fish oil either by eating fish or taking fish oil supplements, tablets, capsules, or pills during pregnancy for the overall development of the child and the well-being of the mother. However, it should be noted that fish oil obtained from the liver of the fish, example – cod liver oil, should not be consumed during pregnancy as cod liver oil is high in retinol and vitamin A, which are usually known to cause birth defects.


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
Oftentimes this could be a result of poor body composition, poor activity levels, or other things, like a low-quality diet. Now, for other people, I do think it’s the case that for people who do not eat fish and for people whose animal products, especially their eggs, are mostly from animals fed grains rather than pasture-raised animals or who don’t eat eggs, I think in those cases there is an argument for fish oil in the sense that those people are probably not going to get enough omega-3 fatty acids, but the better argument might be: Eat pastured eggs or eat fish. Even eating an oily fish like salmon once or twice a week is probably good enough to provide the omega-3 fatty acids that you need. Eating some pastured egg yolks every day is probably good enough to provide for the omega-3 fatty acids that you need.
Fish oil supplements vary in the amounts and ratios of DHA and EPA they contain. For example, salmon oil naturally contains more DHA than EPA; a supplement derived from algae may only contain DHA. Krill oil contains significant amounts of both EPA and DHA. Read the labels and remember whatever supplement you buy, it must have at least 600 mg of DHA.

To reap all the omega-3 benefits, it may be difficult for some people to eat the required amounts of oily fish, particularly with the well-known dangers of farmed fish, which are more readily available to most Americans. That’s why some people consider a high-quality omega-3 supplement in addition to a well-rounded diet. I’ll discuss supplements in a moment, though.
Growing up, Joe was plagued with a myriad of health issues such as gut problems, autoimmune issues, chronic fatigue, brain fog, insomnia, and general inflammation. Both conventional and alternative doctors weren’t able to help him, so he decided to fix himself. With lots of health questions and few satisfying answers, Joe decided to read every research paper he could get his hands on and conduct thousands of experiments on his own body in order to fix his health issues. Joe started SelfHacked in late 2013 when he successfully fixed all of his issues, and now it gets millions of readers a month looking to educate themselves about how they can improve their health. Joe is now a thriving author, speaker, and serial entrepreneur, founding SelfDecode & LabTestAnalyzer.
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:

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).
They also found that taking more long-chain omega 3 fats (including EPA and DHA), primarily through supplements probably makes little or no difference to risk of cardiovascular events, coronary heart deaths, coronary heart disease events, stroke or heart irregularities. Long-chain omega 3 fats probably did reduce some blood fats, triglycerides and HDL cholesterol. Reducing triglycerides is likely to be protective of heart diseases, but reducing HDL has the opposite effect. The researchers collected information on harms from the studies, but information on bleeding and blood clots was very limited. 
Fish oil contamination even among “molecularly distilled” brands and those aimed at children is a widespread problem. One study in California tested 10 common brands and found PCBs — toxic industrial pollutants that have contaminated our oceans — in all of them. Some had 70 times the PCBs of other ones and 240x the toxicity. In another study, researchers tested 13 over-the-counter children’s dietary supplements containing fish oil for PCBs. PCBs were detected in all products. Our family takes algae-derived omega-3 (DHA/EPA) capsules, which are bioequivalent to fish oil capsules. Algae are actually the source where fish get their omega-3 content, so we skip the contaminated middle man (or, fish, in this case) and the neurotoxins that come with them given how polluted our oceans are now. I highly recommend parents do their research on what studies show about fish oil contamination and not just trust the labels, as well as consider algae-derived omega-3 capsules as more healthful bioequivalent to fish oil.
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.

3. DHA affects your child's learning and behavior. Do you want to maximize your child's intellectual potential? A study published in Plos One in June 20138 linked low levels of DHA with poorer reading, and memory and behavioral problems in healthy school-age children. In another study published in the American Journal of Clinical Nutrition in August 2013,9 children who consumed an omega-3 fat supplement as infants scored higher on rule learning, vocabulary, and intelligent testing at ages 3 to 5.
After a large number of lab studies found that omega-3 fatty acids may be effective in slowing or reversing the growth of hormonal cancers, namely prostate and breast cancer cells, animal and human epidemiological studies have been conducted to see whether this effect occurred in real-life scenarios. The evidence is somewhat conflicting in some reports, but there is some evidence to suggest breast and prostate cancers may be potentially slowed (or the risk reduced) in people who eat a lot of oily fish and possibly those who supplement with omega-3. (66, 67, 68)
Fish oil is a commonly used dietary supplement, with sales in the U.S. alone reaching $976 million in 2009.[48] Problems of quality have been identified in periodic tests by independent researchers of marketed supplements containing fish oil and other marine oils. These problems include contamination, inaccurate listing of EPA and DHA levels, spoilage and formulation issues.[49]
Kabir, M., Skurnik, G., Naour, N., Pechtner, V., Meugnier, E., Rome, S., Quignard-Boulange, A., Vidal, H., Slama, G., Clement, K., Guerre-Millo, M., and Rizkalla, S. W. Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am.J.Clin.Nutr. 2007;86(6):1670-1679. View abstract.
One meta-analysis concluded that omega−3 fatty acid supplementation demonstrated a modest effect for improving ADHD symptoms.[39] A Cochrane review of PUFA (not necessarily omega−3) supplementation found "there is little evidence that PUFA supplementation provides any benefit for the symptoms of ADHD in children and adolescents",[40] while a different review found "insufficient evidence to draw any conclusion about the use of PUFAs for children with specific learning disorders".[41] Another review concluded that the evidence is inconclusive for the use of omega−3 fatty acids in behavior and non-neurodegenerative neuropsychiatric disorders such as ADHD and depression.[42]
A scientific review in 2014 evaluated study findings on omega-3 intake in relation to the prevention and treatment of breast cancer, the most prevalent cancer among women. The review found that EPA and DHA, as well as ALA, can differentially inhibit breast tumor development. According to this review, there is solid evidence to support the use of omega-3s as “a nutritional intervention in the treatment of breast cancer to enhance conventional therapeutics, or potentially lowering effective doses.” (16) Additionally, a 2016 study found that “very high fish consumption in early adulthood to midlife may be associated with decreased risk of breast cancer.” (17)

The nutritional value of seafood is important during early development. The Dietary Guidelines for Americans 2015–2020 and guidance from the U.S. Food and Drug Administration and Environmental Protection Agency recommend that women who are pregnant or breastfeeding eat at least 8 ounces but no more than 12 ounces of a variety of seafood each week, from choices that are lower in methyl mercury. Methyl mercury can be harmful to the brain and nervous system if a person is exposed to too much of it. 
Most leafy green vegetables have significant amounts of omega-3, and spinach is no exception. Despite its villainous reputation, raw spinach actually has a mild flavor, making it an ideal base for salads or a crunchy addition to sandwiches. Many people add spinach to eggs, soups, or pasta dishes without impacting flavor. If you’re dealing with a particularly picky eater, though, try some of the recipes in Jessica Seinfeld’s Deceptively Delicious — her spinach and carrot brownies are tasty, healthy, and chocolaty to boot!
In 1964 it was discovered that enzymes found in sheep tissues convert omega−6 arachidonic acid into the inflammatory agent called prostaglandin E2[71] which both causes the sensation of pain and expedites healing and immune response in traumatized and infected tissues.[72] By 1979 more of what are now known as eicosanoids were discovered: thromboxanes, prostacyclins, and the leukotrienes.[72] The eicosanoids, which have important biological functions, typically have a short active lifetime in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. If the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may, however, have deleterious effects.[72] Researchers found that certain omega−3 fatty acids are also converted into eicosanoids, but at a much slower rate. Eicosanoids made from omega−3 fatty acids are often referred to as anti-inflammatory, but in fact they are just less inflammatory than those made from omega−6 fats. If both omega−3 and omega−6 fatty acids are present, they will "compete" to be transformed,[72] so the ratio of long-chain omega−3:omega−6 fatty acids directly affects the type of eicosanoids that are produced.[72]
Pumps the Heart: Where to begin? Omega-3s reduce triglycerides, stabilize your heartbeat, make platelets "less sticky" and can even lower blood pressure. The EPA you get with your daily DHA dose helps prevent artery-blocking clots. In the Iowa Nurses Study (and 3 others), 1 ounce of nuts a day decreased the incidence of heart disease between 20 and 60 percent.
There is some evidence that omega−3 fatty acids are related to mental health,[47] including that they may tentatively be useful as an add-on for the treatment of depression associated with bipolar disorder.[48] Significant benefits due to EPA supplementation were only seen, however, when treating depressive symptoms and not manic symptoms suggesting a link between omega−3 and depressive mood.[48] There is also preliminary evidence that EPA supplementation is helpful in cases of depression.[49] The link between omega−3 and depression has been attributed to the fact that many of the products of the omega−3 synthesis pathway play key roles in regulating inflammation (such as prostaglandin E3) which have been linked to depression.[50] This link to inflammation regulation has been supported in both in vitro[51] and in vivo studies as well as in meta-analysis studies.[33] The exact mechanism in which omega−3 acts upon the inflammatory system is still controversial as it was commonly believed to have anti-inflammatory effects.[52]

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.
The absence of DHA in many pure EPA trials, and therefore lack of competition between EPA and DHA during digestion and consequently for uptake, is considered to be partly responsible for the positive outcomes. Simply put, pure EPA delivers more EPA into cells where it is needed than combined EPA & DHA blends. Consequently, oils containing DHA may not be suitable for a variety of conditions when treatment relies on increasing levels of EPA and its end products.
Belalcazar, L. M., Reboussin, D. M., Haffner, S. M., Reeves, R. S., Schwenke, D. C., Hoogeveen, R. C., Pi-Sunyer, F. X., and Ballantyne, C. M. Marine omega-3 fatty acid intake: associations with cardiometabolic risk and response to weight loss intervention in the Look AHEAD (Action for Health in Diabetes) study. Diabetes Care 2010;33(1):197-199. 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]
Human diet has changed rapidly in recent centuries resulting in a reported increased diet of omega−6 in comparison to omega−3.[83] The rapid evolution of human diet away from a 1:1 omega−3 and omega−6 ratio, such as during the Neolithic Agricultural Revolution, has presumably been too fast for humans to have adapted to biological profiles adept at balancing omega−3 and omega−6 ratios of 1:1.[84] This is commonly believed to be the reason why modern diets are correlated with many inflammatory disorders.[83] While omega−3 polyunsaturated fatty acids may be beneficial in preventing heart disease in humans, the level of omega−6 polyunsaturated fatty acids (and, therefore, the ratio) does not matter.[78][85]
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]
Fish oil contamination even among “molecularly distilled” brands and those aimed at children is a widespread problem. One study in California tested 10 common brands and found PCBs — toxic industrial pollutants that have contaminated our oceans — in all of them. Some had 70 times the PCBs of other ones and 240x the toxicity. In another study, researchers tested 13 over-the-counter children’s dietary supplements containing fish oil for PCBs. PCBs were detected in all products. Our family takes algae-derived omega-3 (DHA/EPA) capsules, which are bioequivalent to fish oil capsules. Algae are actually the source where fish get their omega-3 content, so we skip the contaminated middle man (or, fish, in this case) and the neurotoxins that come with them given how polluted our oceans are now. I highly recommend parents do their research on what studies show about fish oil contamination and not just trust the labels, as well as consider algae-derived omega-3 capsules as more healthful bioequivalent to fish oil.

Cast about for healthy canned tuna. Think all tuna is created equal? Think again. Choose canned light tuna instead of tuna steaks or albacore tuna. It tends to have less mercury. Albacore may contain three times the mercury of chunk light tuna. Check fish guides for the latest information about foods low in toxins but high in omega-3. Two good online sources are:
In 1964 it was discovered that enzymes found in sheep tissues convert omega−6 arachidonic acid into the inflammatory agent called prostaglandin E2[71] which both causes the sensation of pain and expedites healing and immune response in traumatized and infected tissues.[72] By 1979 more of what are now known as eicosanoids were discovered: thromboxanes, prostacyclins, and the leukotrienes.[72] The eicosanoids, which have important biological functions, typically have a short active lifetime in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. If the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may, however, have deleterious effects.[72] Researchers found that certain omega−3 fatty acids are also converted into eicosanoids, but at a much slower rate. Eicosanoids made from omega−3 fatty acids are often referred to as anti-inflammatory, but in fact they are just less inflammatory than those made from omega−6 fats. If both omega−3 and omega−6 fatty acids are present, they will "compete" to be transformed,[72] so the ratio of long-chain omega−3:omega−6 fatty acids directly affects the type of eicosanoids that are produced.[72]
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.
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]
This article had several limitations and the findings need to be considered with caution. First, our participant population is too heterogeneous because of our broad inclusion criteria, which might be true if considering current Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases diagnostic systems. However, the novel Research Domain Criteria consider anxiety to be one of the major domains in Negative Valence Systems. Trials should be conducted in populations in which anxiety is the main symptom irrespective of the presence or absence of diagnosis of anxiety disorder. Second, because of the limited number of recruited studies and their modest sample sizes, the results should not be extrapolated without careful consideration. Third, the significant heterogeneity among the included studies (Cochran Q, 178.820; df, 18; I2, 89.934%; P < .001) with potential influence by some outlier studies, such as the studies by Sohrabi et al56 and Yehuda et al,61 would be another major concern. Therefore, clinicians should pay attention to this aspect when applying the results of the current meta-analysis to clinical practice, particularly when considering the subgroups of these 2 studies (ie, subgroups with specific clinical diagnoses, with <2000 mg/d, with EPA <60%, and with placebo-controlled trials).
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
There is some evidence that omega−3 fatty acids are related to mental health,[47] including that they may tentatively be useful as an add-on for the treatment of depression associated with bipolar disorder.[48] Significant benefits due to EPA supplementation were only seen, however, when treating depressive symptoms and not manic symptoms suggesting a link between omega−3 and depressive mood.[48] There is also preliminary evidence that EPA supplementation is helpful in cases of depression.[49] The link between omega−3 and depression has been attributed to the fact that many of the products of the omega−3 synthesis pathway play key roles in regulating inflammation (such as prostaglandin E3) which have been linked to depression.[50] This link to inflammation regulation has been supported in both in vitro[51] and in vivo studies as well as in meta-analysis studies.[33] The exact mechanism in which omega−3 acts upon the inflammatory system is still controversial as it was commonly believed to have anti-inflammatory effects.[52]
Joensen, A. M., Schmidt, E. B., Dethlefsen, C., Johnsen, S. P., Tjonneland, A., Rasmussen, L. H., and Overvad, K. Dietary intake of total marine n-3 polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid and docosapentaenoic acid and the risk of acute coronary syndrome - a cohort study. Br J Nutr 2010;103(4):602-607. View abstract.
Meta‐analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all‐cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high‐quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high‐quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses – LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted.
Fish oil combined with fenofibrate has not been studied extensively in randomized controlled trials. Data to date, however, suggest that the combination is safe and effective.63,64 A recent randomized controlled trial of 100 patients with severe hypertriglyceridemia and HIV on highly active antiretroviral therapy showed that a regimen of fenofibrate and 3 g/d of fish oil for 8 weeks was well tolerated. The median baseline triglyceride level of 650 mg/dL was reduced by 65%.63 Another recent randomized, 2 month, double-blind, placebo-controlled trial, which was set up to assess the safety and efficacy of fenofibrate with 4 g of fish oil, showed that in the 81 patients assigned to combination therapy, triglyceride levels were reduced by 61%. Therapy was well-tolerated without significant adverse reactions at 8 weeks or at the end of a 2-year open label extension.64 The combination of fish oil and niacin requires further study.
Today, some doctors are starting to measure the omega-3 index levels of their patients, just like they do with cholesterol levels. However, if your doctor does not offer this, several companies provide a quick and easy blood test you can conduct yourself, including OmegaQuant. This company is run by by Dr. William Harris, one of the scientists who initially developed the concept of the omega-3 index.
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

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?]
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.
Human studies also confirm cognition and memory improvement with omega-3 supplementation. For example, a study showed that both fish oil and krill oil enhanced cognitive function in a group of older men by increasing oxygen delivery to their brains. Interestingly, for those taking krill oil this effect was more prominent than those taking fish oil, though both groups were significantly better than placebo.30 As we pointed out earlier, because the omega-3 DHA is bound to phospholipids in krill it may be more effectively incorporated into the critical cell membrane in brain cells.
Two psychiatrists (P.-T.T. and T.-Y.C.) separately performed a systematic literature search of the PubMed, Embase, ProQuest, ScienceDirect, Cochrane Library, ClinicalKey, Web of Science, and ClinicalTrials.gov databases to March 4, 2018. Because we presumed some clinical trials would use investigating scales for some other mood symptoms but also contain symptoms of anxiety, we tried to use some nonspecific medical subject heading terms to include those clinical trials. Therefore, we used the following keywords: omega-3, eicosapentaenoic acid, EPA, DHA, or docosahexaenoic acid; and anxiety, anxiety disorder, generalized anxiety disorder, agoraphobia, panic disorder, or posttraumatic stress disorder. After removing duplicate studies, the same 2 authors screened the search results according to the title and abstract to evaluate eligibility. List of potentially relevant studies were generated for a full-text review. Any inconsistencies were discussed with a third author to achieve final consensus. To expand the list of potentially eligible articles, we performed a manual search of the reference lists of review articles in this area.12,38,39
The randomized trials assessing the efficacy of fish oil supplementation on secondary prevention of CAD lend further evidence to the findings that fish oil may protect from sudden cardiac death.36 The Diet and Reinfarction Trial (DART),37 one of the first randomized trials of fish oil in CAD, has been interpreted as potential support for fish oil’s role in sudden death reduction because the primary outcome of all-cause mortality occurred within 2 months of the trial’s onset.38 After such a short time span, it was believed that atherosclerosis would not be altered and therefore another mechanism was reducing mortality. This was further supported by the fact that nonfatal MIs were not reduced. Although the actual modes of death other than CAD-related deaths were not documented, it has been postulated to be secondary to a reduction in sudden death.39 The Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico-Prevenzione40 (GISSI-Prevenzione) trial, a larger randomized trial of fish oil in CAD, has also been interpreted as evidence for fish oil’s protection against sudden death. Sudden death, however, was not a primary end point. Rather, the reduction in fatal events was driven by a reduction in cardiovascular death, which included coronary death, cardiac death, and sudden death.
For those who do not eat seafood, another way exists for you to get a healthy dose of EPA and DHA each day. Fish oil supplements, which are rich in EPA and DHA, can be made from a variety of fish, with the most common ones being halibut, tuna, salmon, cod liver, mackerel and herring. On average, one 3.5 ounce serving of fatty fish contains about 1 gram of omega-3s, which can be obtained through fish oil supplements, according to MedlinePlus.
Meta‐analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all‐cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high‐quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high‐quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses – LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted.
Most leafy green vegetables have significant amounts of omega-3, and spinach is no exception. Despite its villainous reputation, raw spinach actually has a mild flavor, making it an ideal base for salads or a crunchy addition to sandwiches. Many people add spinach to eggs, soups, or pasta dishes without impacting flavor. If you’re dealing with a particularly picky eater, though, try some of the recipes in Jessica Seinfeld’s Deceptively Delicious — her spinach and carrot brownies are tasty, healthy, and chocolaty to boot!
The effect of fish oil consumption on prostate cancer is controversial,[28][29] as one study showed decreased risk with higher blood levels of DPA, whereas another reported increased risk of more aggressive prostate cancer with higher blood levels of combined EPA and DHA.[30] Some evidence indicated an association between high blood levels of omega-3 fatty acids and an increased prostate cancer risk.[31]

Second, quality matters. It is important to purchase fish oil from a reputable manufacturer that follows Good Manufacturing Practices (GMPs) and takes the necessary steps to purify the oil. In choosing a brand like Nature Made®, the #1 Pharmacist Recommended Omega-3/Fish Oil Brand*, you can rest assured knowing Nature Made has a strong commitment to making quality supplements so you can experience the benefits of fish oil.
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.
Fish oil supplements vary in the amounts and ratios of DHA and EPA they contain. For example, salmon oil naturally contains more DHA than EPA; a supplement derived from algae may only contain DHA. Krill oil contains significant amounts of both EPA and DHA. Read the labels and remember whatever supplement you buy, it must have at least 600 mg of DHA.
Omega-3 fatty acids have been found to play a role in atherosclerosis and peripheral arterial disease (PAD). It is thought that both EPA and DHA improve plaque stability, decrease endothelial activation, and improve vascular permeability, thereby decreasing the chance of experiencing a cardiovascular event (41). It was found that EPA supplementation is associated with significantly higher amounts of EPA in the carotid plaque than placebo (P < 0.0001), which may lead to decreased plaque inflammation and increased stability (42). PAD, a manifestation of atherosclerosis, is characterized by buildup of plaque in the arteries of the leg and can eventually lead to complete blockage of the arteries. EPA+DHA supplementation has been shown to improve endothelial function in patients with PAD by decreasing plasma levels of soluble thrombomodulin from a median value of 33.0 μg/L to 17.0 μg/L (P = 0.04) and improve brachial artery flow–mediated dilation from 6.7% to 10.0% (P = 0.02) (43). Patients who had PAD and were supplemented with EPA experienced a significantly lower major coronary event HR than those who did not take EPA (HR: 0.44; 95% CI: 0.19–0.97; P = 0.041) (44).

While fish oil has plenty of beneficial qualities, there is a lot of hype around its possible applications, and not all of them are accurate, so be wary when reading literature on this useful oil. Fish oil manufacturers have attempted to market it as a remedy for almost anything. We suggest that readers educate themselves fully before making an informed decision, rather than getting affected by both negative and positive propaganda about the beneficial applications of fish oil.
Krill oil is joining the toolkit for fighting arthritis, thanks to its exceptional anti-inflammatory properties resulting from its phospholipid form of omega-3s. A study in mice with experimental arthritis showed that krill oil supplements reduced arthritis scores and markedly diminished joint swelling. When examined under a microscope, the animals’ joints were remarkably free of inflammatory infiltrates of immune system cells.85

Dry eye. Higher intake of fish oil from the diet has been linked to a lower risk of dry eye in women. But the effects of fish oil in people with dry eye are inconsistent. Some research shows that fish oil reduces dry eye symptoms such as pain, blurred vision, and sensitivity. But fish oil doesn’t seem to improve other signs and symptoms of dry eye such as tear production and damage to the surface of the eye. Taking fish oil also doesn’t improve signs and symptoms of dry eye when used with other dry eye treatments.
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