It’s uncertain whether omega-3 fatty acid supplements are helpful for depression. Although some studies have had promising results, a 2015 evaluation of 26 studies that included more than 1,400 people concluded that if there is an effect, it may be too small to be meaningful. Other analyses have suggested that if omega-3s do have an effect, EPA may be more beneficial than DHA and that omega-3s may best be used in addition to antidepressant medication rather than in place of it. 

The U.S. Food and Drug Administration recommends consuming no more than 3 g/day of EPA and DHA combined, including up to 2 g/day from dietary supplements. Higher doses are sometimes used to lower triglycerides, but anyone taking omega-3s for this purpose should be under the care of a healthcare provider because these doses could cause bleeding problems and possibly affect immune function. Any side effects from taking omega-3 supplements in smaller amounts are usually mild. They include an unpleasant taste in the mouth, bad breath, heartburn, nausea, stomach discomfort, diarrhea, headache, and smelly sweat.
If, however, we want to target the actions and benefits of either fat for more intensive support or clinical use, we need to alter the natural 1.5:1 EPA:DHA ratio found in most omega-3 sources such as fish oil – which is when concentrated supplements are especially useful. Certain forms of omega-3 called ethyl-ester and re-esterified triglyceride give nature a helping hand – allowing us to achieve targeted ratios of specific fatty acids at high concentration and physiologically active doses.
Jump up ^ Ilse Schreiber: Die Schwestern aus Memel (1936), quoted, and extract translated in: Strzelczyk, Florentine (2014). "16: 'Fighting against Manitou': German Identity and Ilse Schreiber's Canada Novels Die Schwestern aus Memel (1936) and Die Flucht in Paradies (1939)". In McFarland, Rob; James, Michelle Stott. Sophie Discovers Amerika: German-Speaking Women Write the New World. Studies in German Literature Linguistics and Culture. 148. Boydell & Brewer. p. 207. ISBN 9781571135865. Hoffentlich zogen die Eltern in eine Gegend, wo es recht viele Eingeborene gab. Indianer, die nur von Jagd und Fischfang leben. Ach, und womöglich Eskimos, die sich mit Tran einschmieren, um sich gegen die Kälte zu schützen und rohes Fleisch essen [...]. [She hoped her parents would move to an area where there were many aboriginals. Indians who live solely by hunting and fishing. Oh, and if possible Eskimos who smear themselves with fish oil to protect themselves from the cold, and who eat raw meat.]
Omega−3 fatty acids are important for normal metabolism.[8] Mammals are unable to synthesize omega−3 fatty acids, but can obtain the shorter-chain omega−3 fatty acid ALA (18 carbons and 3 double bonds) through diet and use it to form the more important long-chain omega−3 fatty acids, EPA (20 carbons and 5 double bonds) and then from EPA, the most crucial, DHA (22 carbons and 6 double bonds).[8] The ability to make the longer-chain omega−3 fatty acids from ALA may be impaired in aging.[9][10] In foods exposed to air, unsaturated fatty acids are vulnerable to oxidation and rancidity.[11]
In another study, Australian researchers looked at whether giving infants added omega-3 fatty acids might improve health,4 including reducing their risk for heart disease. They gave 420 infants either an omega 3 supplement or olive oil from birth through six months, then revisited that at age 5 years to see if either group appeared healthier from a heart risk point of view.
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.
Many studies documenting the benefits of omega-3s have been conducted with supplemental daily dosages between 2 and 5 grams of EPA and DHA, more than you could get in 2 servings of fish a week. But that doesn't mean eating fish is an exercise in futility. Many studies document its benefits. For example, a 2003 National Eye Institute study showed that 60- to 80-year-olds eating fish more than twice a week were half as likely to develop macular degeneration as those who ate no fish at all.
And in osteoarthritis, when a DHA/EPA formulation was added to chondroitin sulfate, people experienced more complete relief of symptoms such as stiffness and pain. One study found a significant increase in walking speed in people who supplemented with fish oil versus those who did not.79,80 As with the beneficial results seen in people with bone loss, these positive findings may have been the result of the decreased inflammatory destruction of joint cartilage.81

Thanks for the informative article. You mentioned that those taking high doses of DHA should supplement it with trace amounts of GLA. What GLA source would you recommend, and how much per day? I will be taking around 3400 mg of epa and 2200 mg DHA per day. I've heard that Borage Oil is more potent in GLA than evening primrose, but that it can lead to increased clotting and increased risk of heart attack, stroke, etc due to increased thromboxane B2. The main reason I want to stay away from the primrose is because it is extremely rich in linoleic acid. Thanks.
According to research conducted at Harvard University, omega-3 fatty acid deficiency is officially one of the top 10 causes of death in America, claiming the lives of up to 96,000 people each year. Out of the 12 dietary, lifestyle and metabolic risk factors examined in the study, omega-3 fatty acid deficiency ranked as the sixth highest killer of Americans. (1) These deaths are considered preventable since getting enough omega 3-fatty acids in your diet can ward off this now common cause of death, and fish oil benefits omega-3 intake as a potent omega-3 source.

Omega-3 fatty acids get a fair amount of time in the press and a great deal of respect at this point. But do you know what omega-3s are? What omega-3 benefits could convince you to add more oily fish (or maybe a supplement) to your diet? Are omega-3 foods really that big of a deal when it comes to eating a nutrient-dense diet? Could you be deficient in these fatty acids?


This constant sweeping motion of DHA also causes the breakup of lipid rafts in membranes (8). Disruption of these islands of relatively solid lipids makes it more difficult for cancer cells to continue to survive and more difficult for inflammatory cytokines to initiate the signaling responses to turn on inflammatory genes (9). In addition, the greater spatial characteristics of DHA increase the size of LDL particles to a greater extent compared to EPA. As a result, DHA helps reduce the entry of these enlarged LDL particles into the muscle cells that line the artery thus reducing the likelihood of developing atherosclerotic lesions (10). Thus the increased spatial territory swept out by DHA is good news for making certain areas of membranes more fluid or lipoprotein particles larger, even though it reduces the benefits of DHA in competing with AA for key enzymes important in the development of cellular inflammation.
Fish oil is also commonly used to treat conditions such as Rheumatoid arthritis, high blood pressure, ADHD, menstrual pain, hardening of the arteries or kidney problems. These conditions can be improved by improving blood flow, which omega-3 fatty acids in the blood stream. There is also some evidence that fish oil may help with conditions such as chest pain, liver disease, migraine prevention, gum infections, breast pain, and muscle soreness due to exercise, skin rashes and stomach ulcers.

Khandelwal, S., Demonty, I., Jeemon, P., Lakshmy, R., Mukherjee, R., Gupta, R., Snehi, U., Niveditha, D., Singh, Y., van der Knaap, H. C., Passi, S. J., Prabhakaran, D., and Reddy, K. S. Independent and interactive effects of plant sterols and fish oil n-3 long-chain polyunsaturated fatty acids on the plasma lipid profile of mildly hyperlipidaemic Indian adults. Br.J.Nutr. 2009;102(5):722-732. View abstract.
One reason omega-3 fatty acids may be so beneficial to this many aspects of health could be that they help decrease system-wide inflammation. (49, 50, 51, 52, 53) Inflammation is at the root of most diseases and is related to the development of nearly every major illness, so by eating a nutrient-dense, anti-inflammatory diet, you give your body its best chance to fight disease like it was designed to do.
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.
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)
Since EPA and DHA are both essential for health and appear together in nature, many studies have attempted to treat clinical conditions with combined EPA and DHA oils, but the outcomes have been varied, contradictory and disappointing. Consequently, researchers have started to investigate the individual actions of EPA and DHA in isolation, in numerous health conditions where an omega-3 deficiency is related to symptoms or known to play a causative role. The emerging evidence shows marked differences between how these two fatty acids affect us – not just at the cellular level but also the body as a whole.
Omega-3 is a group of long-chain polyunsaturated fatty acids, perhaps most notably found in fatty fish. As science parses the biological actions of nutrients, it turns out that omega-3 fats do many good things for the body and the brain. Known as an "essential" fatty acid, meaning the body must take it in from food sources, omega-3 is important to human metabolism.
Soy can get a bad rap — and may indeed cause problems for people with certain food sensitivities — but this delicious bean is one of the most powerful (and versatile) ways to add omega-3 to your diet. Whole soybeans (known as edamame) are a favorite protein-packed snack for vegetarians; more processed forms (including tofu, soy milk, and soybean-based cooking oil) make soy infinitely more accessible. For some ideas, check out the 1998 classic, The Whole Soy Cookbook, which outlines how to cook with soy-based products ranging from miso to tempeh and beyond.
(How much omega-3 is necessary to increase one’s omega-3 index?  Studies show it can take between 1800 – 2000 mg of EPA/DHA daily to move a person’s index by 4 – 5 percentage points (12). Importantly, this is a much larger dose than you’d get swallowing one or two regular fish oil capsules and could well explain why many traditional omega-3 products fail to deliver results.)

An 18-month study was published in 2014 that evaluated how borage seed oil — rich in GLA — and fish oil rich fared against each other in treating patients with rheumatoid arthritis. It was discovered that all three groups (one taking fish oil, one taking borage oil and one taking a combination of the two) “exhibited significant reductions” in disease activity, and no therapy outperformed the others. For all three, “meaningful clinical responses” were the same after nine months. (11)
It’s no surprise that fish — particularly cold-water fatty fish like salmon, mackerel, and anchovies — are rich in omega-3s. It’s called fish oil for a reason, right? Mackerel, for instance, may have more than 3300 mg of omega-3 per serving — that’s more than 6 times the recommended per day dose for healthy adults. Not a huge fish connoisseur? Try some of the quick, simple recipes in Cooking with Fish Like a Pro, an accessible collection of fish recipes to suit every palate.

Fish oil has been shown to have a direct electrophysiological effect on the myocardium. Initial experience with animal ischemia models demonstrated that the ventricular fibrillation threshold was increased in both animals fed or infused with omega-3 FA.23,24 This progressed to a demonstration, on a cellular and ion channel level, that omega-3 FA reduce both sodium currents and L-type calcium currents.25–29 It is hypothesized that during ischemia, a reduction in the sodium ion current protects hyperexcitable tissue, and a reduction in the calcium ion current reduces arrhythmogenic depolarizing currents.30
In lab experiments, animals given krill showed improved navigation skills. What this means is that they achieved higher levels of cognition and memory required to navigate complex territory.28 In addition, research shows that animals supplemented with krill oil showed significantly fewer signs of depression and resignation. This improvement in mood was equivalent to the effect of the prescription anti-depressant drug imipramine (Tofranil®).29
Flaxseed (or linseed) (Linum usitatissimum) and its oil are perhaps the most widely available botanical source of the omega−3 fatty acid ALA. Flaxseed oil consists of approximately 55% ALA, which makes it six times richer than most fish oils in omega−3 fatty acids.[126] A portion of this is converted by the body to EPA and DHA, though the actual converted percentage may differ between men and women.[127]
Interestingly, the results are also consistent with our recent findings that somatic anxiety is associated with omega-3 PUFA deficits and the genetic risks of PUFA metabolic enzyme cytosolic phospholipase A2 in major depressive disorder62,63 and interferon α–induced neuropsychiatric syndrome.63,64 Brain membranes contain a high proportion of omega-3 PUFAs and their derivatives and most animal and human studies suggest that a lack of omega-3 PUFAs in the brain might induce various behavioral and neuropsychiatric disorders,16,65-70 including anxiety-related behaviors.12,18,19,32,49,71 Emerging evidence suggests that omega-3 PUFAs interfere with and possibly control several neurobiological processes, such as neurotransmitter systems, neuroplasticity, and inflammation,12,72 which is postulated to be the mechanism underlying anxiety and depression.
Fish oil is oil derived from the tissues of oily fish. Fish oils contain the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), precursors of certain eicosanoids that are known to reduce inflammation in the body,[1][2] and have other health benefits, such as treating hypertriglyceridemia, although claims of preventing heart attacks or strokes have not been supported.[3][4][5][6] Fish oil and omega-3 fatty acids have been studied in a wide variety of other conditions, such as clinical depression,[7][8] anxiety,[9][10][11] cancer, and macular degeneration, yet benefits in these conditions have not been verified.[12]
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.

This constant sweeping motion of DHA also causes the breakup of lipid rafts in membranes (8). Disruption of these islands of relatively solid lipids makes it more difficult for cancer cells to continue to survive and more difficult for inflammatory cytokines to initiate the signaling responses to turn on inflammatory genes (9). In addition, the greater spatial characteristics of DHA increase the size of LDL particles to a greater extent compared to EPA. As a result, DHA helps reduce the entry of these enlarged LDL particles into the muscle cells that line the artery thus reducing the likelihood of developing atherosclerotic lesions (10). Thus the increased spatial territory swept out by DHA is good news for making certain areas of membranes more fluid or lipoprotein particles larger, even though it reduces the benefits of DHA in competing with AA for key enzymes important in the development of cellular inflammation.
Children: Fish oil is POSSIBLY SAFE when taken by mouth appropriately. Fish oil has been used safely through feeding tubes in infants for up to 9 months. But young children should not eat more than two ounces of fish per week. Fish oil is POSSIBLY UNSAFE when consumed from dietary sources in large amounts. Fatty fish contain toxins such as mercury. Eating contaminated fish frequently can cause brain damage, mental retardation, blindness and seizures in children.
“The review provides good evidence that taking long-chain omega 3 (fish oil, EPA or DHA) supplements does not benefit heart health or reduce our risk of stroke or death from any cause.  The most trustworthy studies consistently showed little or no effect of long-chain omega 3 fats on cardiovascular health. On the other hand, while oily fish is a healthy food, it is unclear from the small number of trials whether eating more oily fish is protective of our hearts. 
In the United States, the Institute of Medicine publishes a system of Dietary Reference Intakes, which includes Recommended Dietary Allowances (RDAs) for individual nutrients, and Acceptable Macronutrient Distribution Ranges (AMDRs) for certain groups of nutrients, such as fats. When there is insufficient evidence to determine an RDA, the institute may publish an Adequate Intake (AI) instead, which has a similar meaning, but is less certain. The AI for α-linolenic acid is 1.6 grams/day for men and 1.1 grams/day for women, while the AMDR is 0.6% to 1.2% of total energy. Because the physiological potency of EPA and DHA is much greater than that of ALA, it is not possible to estimate one AMDR for all omega−3 fatty acids. Approximately 10 percent of the AMDR can be consumed as EPA and/or DHA.[105] The Institute of Medicine has not established a RDA or AI for EPA, DHA or the combination, so there is no Daily Value (DVs are derived from RDAs), no labeling of foods or supplements as providing a DV percentage of these fatty acids per serving, and no labeling a food or supplement as an excellent source, or "High in..."[citation needed] As for safety, there was insufficient evidence as of 2005 to set an upper tolerable limit for omega−3 fatty acids,[105] although the FDA has advised that adults can safely consume up to a total of 3 grams per day of combined DHA and EPA, with no more than 2 g from dietary supplements.[8]
Good points, Miroslav. Focusing on your 4th point, with so many different formulations on the market that contain various preservatives, only looking at the blood levels of omega-3’s as the flag for increased risk for prostate cancer tends to ignore the fact that certain populations in coastal regions maintain a diet high in omega fish oils and don’t have a marked increase level of prostate cancer, pointing to the fact that another agent may be to blame here.

Cardiovascular disease is the cause of 38% of all deaths in the United States, many of which are preventable (28). Chronic inflammation is thought to be the cause of many chronic diseases, including cardiovascular disease (29). EPA and DHA are thought to have antiinflammatory effects and a role in oxidative stress (30) and to improve cellular function through changes in gene expression (31). In a study that used human blood samples, EPA+DHA intake changed the expression of 1040 genes and resulted in a decreased expression of genes involved in inflammatory and atherogenesis-related pathways, such as nuclear transcription factor κB signaling, eicosanoid synthesis, scavenger receptor activity, adipogenesis, and hypoxia signaling (31). Circulating markers of inflammation, such as C-reactive protein (CRP), TNF α, and some ILs (IL-6, IL-1), correlate with an increased probability of experiencing a cardiovascular event (32). Inflammatory markers such as IL-6 trigger CRP to be synthesized by the liver, and elevated levels of CRP are associated with an increased risk of the development of cardiovascular disease (33). A study of 89 patients showed that those treated with EPA+DHA had a significant reduction in high-sensitivity CRP (66.7%, P < 0.01) (33). The same study also showed a significant reduction in heat shock protein 27 antibody titers (57.69%, P < 0.05), which have been shown to be overexpressed in heart muscle cells after a return of blood flow after a period of ischemia (ischemia-reperfusion injury) and may potentially have a cardioprotective effect (33).
The differing actions of EPA and DHA, together with their competitive uptake, help to explain why studies that attempt to use standard fish oil therapeutically (where DHA and EPA are combined, in a natural ratio of approximately 1.5:1) are either less beneficial than expected, or even completely ineffective. Standard EPA/DHA fish oils are more suitable for everyday wellbeing, to compensate for a lack of fish in the diet and to meet a suggested intake.
Results of studies investigating the role of LCPUFA supplementation and LCPUFA status in the prevention and therapy of atopic diseases (allergic rhinoconjunctivitis, atopic dermatitis and allergic asthma) are controversial; therefore, at the present stage of our knowledge (as of 2013) we cannot state either that the nutritional intake of n−3 fatty acids has a clear preventive or therapeutic role, or that the intake of n-6 fatty acids has a promoting role in context of atopic diseases.[64]
56. Davidson MH, Stein EA, Bays HE, et al. COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29:1354–1367. [PubMed]
For patients without documented CAD, the American Heart Association 2006 Diet and Lifestyle Recommendations advise the consumption of at least 2 servings of fish per week, preferably fatty fish high in DHA and EPA.65 The guidelines also recommend a daily fish intake equivalent to 1 g/d of EPA and DHA for secondary prevention of CAD. Fish oil supplements containing EPA and DHA are suggested as an alternative to fatty fish consumption for secondary prevention.

Not surprising, there are some areas in which both EPA and DHA appear to be equally beneficial. As an example, both are equally effective in reducing triglyceride levels (10). This is probably due to the relatively equivalent activation of the gene transcription factor (PPAR alpha) that causes the enhanced synthesis of the enzymes that oxidize fats in lipoprotein particles. There is also apparently equal activation of the anti-inflammatory gene transcription factor PPAR-gamma (11). Both seem to be equally effective in making powerful anti-inflammatory eicosanoids known as resolvins (12). Finally, although both have no effect on total cholesterol levels, DHA can increase the size of LDL particle to a greater extent than can EPA (10).

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.
For several years now, the fish oil and Alzheimer’s disease connection has been studied with consistent results. The essential fatty acids vital for brain function that are found in fish oil can not only slow cognitive decline, but can help prevent brain atrophy in older adults. A study published in the FASEB Journal looked at the health effects of four- to 17-month dietary supplementation with omega-3 fatty acids and antioxidants. The findings once again confirm the potential for fish oil to be used as a weapon to fend off the onset of cognitive decline and Alzheimer’s disease. (8)

Saito, Y., Yokoyama, M., Origasa, H., Matsuzaki, M., Matsuzawa, Y., Ishikawa, Y., Oikawa, S., Sasaki, J., Hishida, H., Itakura, H., Kita, T., Kitabatake, A., Nakaya, N., Sakata, T., Shimada, K., and Shirato, K. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis 2008;200(1):135-140. View abstract.
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