The competition between EPA and DHA during digestion and absorption and the fact that DHA appears to ‘block’ the therapeutic actions of EPA can therefore be an issue if we are looking to optimise the benefits associated with EPA (Martins 2009; Bloch & Qawasmi et al, 2011; Sublette et al, 2011). High dose, high concentration and high ratio EPA supplements increase the effectiveness in depression studies, and pure EPA-only is optimal. Depression is also a condition with an inflammatory basis, so this is likely another significant reason for EPA being the key player – its antagonistic relationship with the inflammatory omega-3 AA (arachidonic acid) is very effective at reducing inflammation.
Guallar, E., Aro, A., Jimenez, F. J., Martin-Moreno, J. M., Salminen, I., van't Veer, P., Kardinaal, A. F., Gomez-Aracena, J., Martin, B. C., Kohlmeier, L., Kark, J. D., Mazaev, V. P., Ringstad, J., Guillen, J., Riemersma, R. A., Huttunen, J. K., Thamm, M., and Kok, F. J. Omega-3 fatty acids in adipose tissue and risk of myocardial infarction: the EURAMIC study. Arterioscler.Thromb.Vasc.Biol 1999;19(4):1111-1118. View abstract.
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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.

Metagenics offers a wide range of educational opportunities including webinars, group meetings, and seminars as part of our commitment to continuing functional medicine education. Our goal is to give our practitioners further insight to help address their patients’ unique health needs for a higher level of personalized, lifetime wellness care. We have been sharing this ever-growing body of nutritional and lifestyle research for over 25 years.


The three types of omega-3s are APA, EPA and DHA. The first is a medium-chain fatty acid and must be converted into EPA before being synthesized by the body, and only about 1 percent of the APA consumed is able to be converted. EPA and DHA are already in a form ready to be synthesized (and are the subject of most scientific research regarding omega-3s).
The bottom line of all that is that there was no clear health benefit from consuming omega-3 fatty acids in food or supplements. There was a suggestion of a possible benefit from LCn3 on cardiac events, but this did not hold up when they took into consideration the quality of the evidence. The better trials, with less risk of bias, tended to be negative.

Giacco, R., Cuomo, V., Vessby, B., Uusitupa, M., Hermansen, K., Meyer, B. J., Riccardi, G., and Rivellese, A. A. Fish oil, insulin sensitivity, insulin secretion and glucose tolerance in healthy people: is there any effect of fish oil supplementation in relation to the type of background diet and habitual dietary intake of n-6 and n-3 fatty acids? Nutr.Metab Cardiovasc.Dis. 2007;17(8):572-580. View abstract.


Because of the preliminary state of knowledge on the effects of omega-3 PUFA treatment on anxiety, we decided to include as many studies as possible and not to set further limitations on specific characteristics, such as length of study, diagnosis, omega-3 PUFA dosage, omega-3 PUFA preparation (EPA to DHA ratio), rated anxiety coding scale, or type of control. Therefore, we chose to make the inclusion criteria as broad as possible to avoid missing any potentially eligible studies. The inclusion criteria included clinical trials in humans (randomized or nonrandomized), studies investigating the effects of omega-3 PUFA treatment on anxiety symptoms, and formal published articles in peer-reviewed journals. The clinical trials could be placebo controlled or non–placebo controlled. The target participants could include healthy volunteers, patients with psychiatric illness, and patients with physical illnesses other than psychiatric illnesses. The exclusion criteria included case reports or series, animal studies or review articles, and studies not investigating the effects of omega-3 PUFA treatment on anxiety symptoms. We did not set any language limitation to increase the number of eligible articles. Figure 1 shows the literature search and screening protocol.

For preventing and reversing the progression of hardening of the arteries after angioplasty: 6 grams of fish oil daily starting one month before angioplasty and continuing for one months after, followed by 3 grams daily for 6 months thereafter has been used. Also, 15 grams of fish oil has been taken daily for 3 weeks before angioplasty and for 6 months thereafter.


Dry eye. Some clinical research shows that eating more fish oil is linked to a lower risk of getting dry eye syndrome in women. Other research shows that taking a specific fish oil product (PRN Dry Eye Omega Benefits softgels) daily modestly improves symptoms of dry eye such as pain, blurred vision, and sensitivity. Other research using other forms of fish oil products suggests that taking these supplements for 4-12 weeks modest improves some dry eye symptoms. However, the sensation of eye dryness is not always improved. Other research also shows that taking a specific combination products containing fish oil and other ingredients might improve some dry eye symptoms; however, this research is conflicted and poor quality.

Due to the anticipated heterogeneity, a random-effects meta-analysis was chosen rather than a fixed-effects meta-analysis because random-effects modeling is more stringent and incorporates an among-study variance in the calculations. The entire meta-analysis procedure was performed on the platform of Comprehensive Meta-analysis statistical software, version 3 (Biostat). Under the preliminary assumption that the scales for anxiety symptoms are heterogeneous among the recruited studies, we chose Hedges g and 95% confidence intervals to combine the effect sizes, in accordance with the manual of the Comprehensive Meta-analysis statistical software, version 3. Regarding the interpretation of effect sizes, we defined Hedges g values 0 or higher as a better association of treatment with reduced anxiety symptoms of omega-3 PUFAs than in controls. For each analysis, a 2-tailed P value less than .05 was considered to indicate statistical significance. When more than 1 anxiety scale was used in a study, we chose the one with the most informative data (ie, mean and standard deviation [SD] before and after treatment). We entered the primary outcome provided in the included articles or obtained from the original authors. As for the variance imputation, we mainly chose the mean and SD before and after treatment. Later, we entered the mean and SD and calculated the effect sizes based on the software option, standardized by post score SD. In the case of studies with 2 active treatment arms, we merged the 2 active treatment arms into 1 group. If these 2 active treatment arms belonged to different subgroups (ie, different PUFA dosage subgroups), we kept them separate. Regarding the numbers of participants counted, we chose intention-to-treat as our priority. If there were insufficient data in the intention to treat group (ie, some studies only provided the changes in anxiety severity in those participants completing trials), we chose instead the per-protocol numbers of participants.
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.
Norris, J. M., Yin, X., Lamb, M. M., Barriga, K., Seifert, J., Hoffman, M., Orton, H. D., Baron, A. E., Clare-Salzler, M., Chase, H. P., Szabo, N. J., Erlich, H., Eisenbarth, G. S., and Rewers, M. Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes. JAMA 9-26-2007;298(12):1420-1428. View abstract.
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.
In addition to depression, chronic stress leads to loss of volume of the hippocampus—and also causes enlargement of the amygdala, the portion of the brain that regulates anxiety and anger.24 When rats were supplemented with omega-3s during exposure to stress, they showed lower corticosterone levels (a marker of stress), and improved learning on a maze—indicating that the omega-3s helped preserve memory and reduce anxiety.24
Widenhorn-Müller  K, Schwanda  S, Scholz  E, Spitzer  M, Bode  H.  Effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): a randomized placebo-controlled intervention trial.  Prostaglandins Leukot Essent Fatty Acids. 2014;91(1-2):49-60. doi:10.1016/j.plefa.2014.04.004PubMedGoogle ScholarCrossref
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]
Gorjao, R., Verlengia, R., Lima, T. M., Soriano, F. G., Boaventura, M. F., Kanunfre, C. C., Peres, C. M., Sampaio, S. C., Otton, R., Folador, A., Martins, E. F., Curi, T. C., Portiolli, E. P., Newsholme, P., and Curi, R. Effect of docosahexaenoic acid-rich fish oil supplementation on human leukocyte function. Clin Nutr 2006;25(6):923-938. View abstract.
The US National Institutes of Health lists three conditions for which fish oil and other omega-3 sources are most highly recommended: hypertriglyceridemia (high triglyceride level), preventing secondary cardiovascular disease, and hypertension (high blood pressure). It then lists 27 other conditions for which there is less evidence. It also lists possible safety concerns: "Intake of 3 grams per day or greater of omega-3 fatty acids may increase the risk of bleeding, although there is little evidence of significant bleeding risk at lower doses. Very large intakes of fish oil/omega-3 fatty acids may increase the risk of hemorrhagic (bleeding) stroke."[12]
Good for you for eating healthily! Sadly, many people do not like omega-3 containing foods such as fish, and for these people, supplementation may be a good alternative to obtain omega-3. As a clinical investigator, my research focuses on study supplements, which is what I was asked to cover in this article. I’m all for healthy eating, but not everyone can afford it or wants to eat certain foods, and this is perhaps why supplements are so popular.

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
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.
It seems that infancy and childhood are some of the most important periods of time in a person’s life to get plenty omega-3s in their diet, probably because of the amount of long-chain fatty acids found in the brain and retina. It’s crucial for developing babies and children to get a good amount of DHA and EPA so their brains and eyes develop fully and properly. (78)
Thanks to fatdog11 for that informative post about PCB’s in fish-oil supplements. Are these same toxicity levels found in fish themselves, or possibly are these levels so high only in highly concentrated fish-oil products? Also, can fatdog11 please inform us more about algae-derived omega-3. What are the DHA and EPA levels in these capsules? What is the cost, and where can they be purchased?

If we want to deliver the benefits associated with EPA therapeutically, it is essential to optimise digestion and uptake. If we take EPA and DHA in their natural 1.5:1 ratio, it’s an uphill struggle for EPA because we know that DHA is more effectively absorbed and assimilated into cells. Delivering the benefits of EPA (for example, for cognitive function, mood and depression, inflammation regulation, heart health, skin health and so on), requires doses of EPA in excess of DHA, which determines the type of benefits obtained and the degree of the beneficial outcomes. The higher the ratio of EPA to DHA (meaning higher doses of EPA in relation to DHA), the more likely that EPA will be digested and absorbed, ready to meet the body’s high demands for this important nutrient.


People should get most of their nutrients from food, advises the federal government's Dietary Guidelines for Americans. Foods contain vitamins, minerals, dietary fiber, and other substances that benefit health. In some cases, fortified foods and dietary supplements may provide nutrients that otherwise may be consumed in less-than-recommended amounts. For more information about building your own healthy eating pattern, visit ChooseMyPlate.gov. MyPlate offers messages, resources, and tools to help you make the choices that are right for you, based on the Dietary Guidelines for Americans.
The health benefits of fish oil include its ability to aid in weight loss and healthy pregnancy. It also promotes fertility and skin care (particularly for psoriasis and acne). It is beneficial in the treatment of various heart diseases, high cholesterol, depression, anxiety, ADHD, weak immune system, cancer, diabetes, inflammation, arthritis, IBD, AIDS, Alzheimer’s disease, eye disorders, macular degeneration, and ulcers.
The #1 Pharmacist Recommended Omega-3/Fish Oil brand,* Nature Made fish oil supply comes from deep ocean waters, not farm-raised fish. State-of-the-art purification processes remove mercury and ensure high levels of fish oil purity and concentration, guaranteed to pass the stringent standards of the Global Organization for EPA and DHA Omega-3 Voluntary Monograph.‡
Thusgaard, M., Christensen, J. H., Morn, B., Andersen, T. S., Vige, R., Arildsen, H., Schmidt, E. B., and Nielsen, H. Effect of fish oil (n-3 polyunsaturated fatty acids) on plasma lipids, lipoproteins and inflammatory markers in HIV-infected patients treated with antiretroviral therapy: a randomized, double-blind, placebo-controlled study. Scand.J.Infect.Dis. 2009;41(10):760-766. View abstract.

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)
We’ve already seen that fish oil can help with depression-like symptoms in rats, but what about people? A study published in the journal Nutritional Neuroscience evaluated the effects of fish oil supplementation on prefrontal metabolite concentrations in adolescents with major depressive disorder. Researchers found that there was a 40 percent decrease in major depression disorder symptoms in addition to marked improvements in amino acid and nutrition content in the brain, specifically, the right dorsolateral prefrontal cortex. (21)
Currently, there isn’t a set standard recommendation for how many omega-3s we need each day, but suggestions range from a fish oil dosage of 500 to 1,000 milligrams daily depending on whom you ask. How easy is it to get these recommended amounts? To give you an idea, there are more than 500 milligrams of total omega-3s in one can of tuna fish and one small serving of wild-caught salmon.

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.
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]

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
Consumers of oily fish should be aware of the potential presence of heavy metals and fat-soluble pollutants like PCBs and dioxins, which are known to accumulate up the food chain. After extensive review, researchers from Harvard's School of Public Health in the Journal of the American Medical Association (2006) reported that the benefits of fish intake generally far outweigh the potential risks.
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. 
Hamazaki, K., Itomura, M., Huan, M., Nishizawa, H., Sawazaki, S., Tanouchi, M., Watanabe, S., Hamazaki, T., Terasawa, K., and Yazawa, K. Effect of omega-3 fatty acid-containing phospholipids on blood catecholamine concentrations in healthy volunteers: a randomized, placebo-controlled, double-blind trial. Nutrition 2005;21(6):705-710. View abstract.

For dry eye: Fish oil supplements providing EPA 360-1680 mg and DHA 240-560 mg have been used for 4-12 weeks. Some people used the specific product (PRN Dry Eye Omega Benefits softgels). A specific combination product containing EPA 450 mg, DHA 300 mg, and flaxseed oil 1000 mg (TheraTears Nutrition, Advanced Nutrition Research) has been used once daily for 90 days.
The supplements contain omega-3 fatty acids, the polyunsaturated oils prominent in fatty cold water fish like salmon, sardines and mackerel. In many observational studies, people who regularly consumed fish two or more times a week were less likely to suffer heart attacks, strokes and cardiovascular deaths than those who ate fish infrequently or not at all.
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.
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.

Peroxides can be produced when fish oil spoils. A study commissioned by the government of Norway concluded there would be some health concern related to the regular consumption of oxidized (rancid) fish/marine oils, particularly in regards to the gastrointestinal tract, but there is not enough data to determine the risk. The amount of spoilage and contamination in a supplement depends on the raw materials and processes of extraction, refining, concentration, encapsulation, storage and transportation.[51] ConsumerLab.com reports in its review that it found spoilage in test reports it ordered on some fish oil supplement products.[52]
Omega-3 fats may also impact the development of arthritis. As far back as 1959, studies were published about the effectiveness of cod liver oil on arthritic patients. In the 1959 study, 93 percent of participants “showed major clinical improvement.” (73) While there is no evidence that high omega-3 levels can prevent the development of arthritis, it seems clear that they can reduce inflammation that causes the typical bone and joint pain experienced in the disease. (74)
Scaly, itchy skin (eczema). Fish oil might help PREVENT eczema, but research is not consistent. Some early research suggests that mothers who take fish oil supplements during pregnancy reduce the risk of severe eczema in their infants. Also, population research suggests that children who eat fish at least once weekly from 1 to 2 years of age have a lower risk of developing eczema. But other research, including recent studies, suggests that neither supplementation during pregnancy nor supplementation during infancy reduces the risk of eczema. Overall, research suggests that fish oil does not help TREAT eczema once it has developed.
A lot of the benefit of fish oil seems to come from the omega-3 fatty acids that it contains. Interestingly, the body does not produce its own omega-3 fatty acids. Nor can the body make omega-3 fatty acids from omega-6 fatty acids, which are common in the Western diet. A lot of research has been done on EPA and DHA, two types of omega-3 acids that are often included in fish oil supplements.
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