The chemical structure of eicosapentaenoic acid and docosahexaenoic acid. Eicosapentaenoic acid consists of 20 carbons (C20) with 5 double bonds, and the last unsaturated carbon is located third from the methyl end (n-3). Do-cosahexaenoic acid consists of 22 carbons (C22) with 6 double bonds, and also with the3 last unsaturated carbon located third from the methyl end (n-3). Adapted with permission from Frishman et al, eds. Cardiovascular Pharmacotherapeutics. New York, NY: McGraw Hill; 2003.3
In recent years, many people – particularly those who strictly follow a vegetarian or vegan diet – have believed that they do not have to consume animal products to get omega-3s, as long as they are consuming high amounts of plant-based omega-3s. But, as I mentioned before, most of the health benefits that you can get from omega-3 fats are linked to animal-based EPA and DHA fats – not plant-based ALA. They are simply NOT interchangeable.
Omega-3 FA most likely reduce serum triglyceride levels by modulating very-low-density lipoprotein (VLDL) and chylomicron metabolism. There is a consistent finding in the literature that the end effect of fish oil is decreased hepatic secretion of VLDL17—the major endogenous source of triglycerides. This effect occurs most likely through multiple mechanisms, including: (1) decreased synthesis of triglycerides because these omega-3 FA may not be the preferred substrates of the enzyme diacylglycerol O-acyltransferase,18 or they may interact with nuclear transcription factors that control lipogenesis19; cellular metabolism consequently shifts toward a decrease in triglyceride synthesis and an increase in FA oxidation; and (2) the promotion of apolipoprotein B degradation in the liver through the stimulation of an autophagic process.20 This means that fewer VLDL particles can be assembled and secreted. Fish oil may also accelerate VLDL and chylomicron clearance21 by inducing lipoprotein lipase activity.22
However, in both observational studies and controlled clinical trials, eating fish was shown to foster optimal development of a baby’s brain and nervous system, prompting advice that pregnant women and nursing mothers eat more fish rich in omega-3s while avoiding species that may contain mercury or other contaminants like PCBs sometimes found in freshwater fish.
Even healthy oils form trans fats when heated. Each oil has a different temperature at which it forms its own trans fats. Generally, when the oil begins to smoke is when trans fats are formed. Did this study consider how and at what temperatures the fish were cooked? Are some of the suppliments heated before being made into capsules? Did it also consider that many types of fish have dangerous levels of mercury?

42. Cawood AL, Ding R, Napper FL, Young RH, Williams JA, Ward MJ, Gudmundsen O, Vige R, Payne SP, Ye S, et al. Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. Atherosclerosis. 2010;212:252–9. [PubMed]

The FDA recommends that consumers do not exceed more than three grams per day of EPA and DHA combined, with no more than 2 grams from a dietary supplement.[56] This is not the same as 3000 mg of fish oil. A 1000 mg pill typically has only 300 mg of omega-3; 10 such pills would equal 3000 mg of omega-3. According to the European Food Safety Authority's (EFSA) Panel on Dietetic Products, Nutrition and Allergies, supplementation of 5 grams of EPA and DHA combined does not pose a safety concern for adults.[57] Dyerberg studied healthy Greenland Inuit and found an average intake of 5.7 grams of omega-3 EPA per day; among other effects these people had prolonged bleeding times, i.e., slower blood clotting.[58]

^ 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.
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.
Rondanelli, M., Giacosa, A., Opizzi, A., Pelucchi, C., La, Vecchia C., Montorfano, G., Negroni, M., Berra, B., Politi, P., and Rizzo, A. M. Effect of omega-3 fatty acids supplementation on depressive symptoms and on health-related quality of life in the treatment of elderly women with depression: a double-blind, placebo-controlled, randomized clinical trial. J.Am.Coll.Nutr. 2010;29(1):55-64. View abstract.

Funding/Support: The work was supported in part by grant 17H04253, Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science; grant 30-A-17 from the National Cancer Center Research and Development Fund; grants MOST106-2314-B-039-027-MY, 106-2314-B-038-049, 106-2314-B-039-031, 106-2314-B-039-035, 104-2314-B-039-022-MY2, and 104-2314-B-039-050-MY3 from the Ministry of Science and Technology, Taiwan; grant HRI-EX105-10528NI from the National Health Research Institutes, Taiwan; and grants CRS-106-063, DMR-107-202, and DMR-107-204 from the China Medical University, Taiwan.


Nielsen, A. A., Jorgensen, L. G., Nielsen, J. N., Eivindson, M., Gronbaek, H., Vind, I., Hougaard, D. M., Skogstrand, K., Jensen, S., Munkholm, P., Brandslund, I., and Hey, H. Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acids. Aliment.Pharmacol.Ther. 2005;22(11-12):1121-1128. View abstract.
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 Japanese notably have the lowest levels of coronary heart disease mortality and atherosclerosis among developed nations — a phenomena that has been largely subscribed to diet. However, even within Japan, a 10-year study of over 41,000 people found that higher intakes of omega-3s were associated with lower risks of nonfatal coronary events (8). A more recent study also found that Japanese with higher omega-3 index levels (10%) had a lower risk of fatal coronary heart disease than those with a lower omega-3 index levels (8%) (9). The study begs the question of whether maybe even the Japanese have room to improve their omega-3 intake and whether 8% should be considered the lower limit of a desirable range.
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From the time of your pregnancy through your child's later life, omega-3 fats DHA and EPA have a radically important role in her brain health and other functions. I recommend supplementing with krill oil before and during pregnancy, and while you breastfeed. Babies receive DHA through your breast milk, so continuing breastfeeding through the first year will give your child a great headstart for health and success.
Heart rate variability, a possible surrogate outcome for the risk of sudden death, was assessed in a randomized trial of myocardial infarction (MI) survivors with an ejection fraction of 40%. In the 49 patients that were randomized to either fish oil or olive oil, Holter monitor recordings showed an increase in heart rate variability in the fish oil group.31 In a larger cohort assessed in the Japan EPA Lipid Intervention Study (JELIS),32 however, no difference in heart rate variability could be attributed to fish oil.
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 Japanese notably have the lowest levels of coronary heart disease mortality and atherosclerosis among developed nations — a phenomena that has been largely subscribed to diet. However, even within Japan, a 10-year study of over 41,000 people found that higher intakes of omega-3s were associated with lower risks of nonfatal coronary events (8). A more recent study also found that Japanese with higher omega-3 index levels (10%) had a lower risk of fatal coronary heart disease than those with a lower omega-3 index levels (8%) (9). The study begs the question of whether maybe even the Japanese have room to improve their omega-3 intake and whether 8% should be considered the lower limit of a desirable range.


Whilst EPA and DHA are both considered to be important regulators of immunity, platelet aggregation and inflammation, their health-influencing by-products arise from very different pathways and their effects in the body differ. DHA is the most abundant omega-3 fatty acid in cell membranes, present in all organs and most abundant in the brain and retina, playing an important structural role. EPA is present structurally only in minute quantities, always being utilised and under constant demand to be replaced. Whilst DHA provides mainly a structural role, it is becoming evident that EPA may be the dominant functional fatty acid out of the two in many areas of health and especially in inflammatory conditions.
Like I mentioned earlier, there are no official guidelines for the proper amount of omega-3s you should consume each day. However, most organization agree that at least 2 servings of a 3.5 ounce serving of fish (preferably oily) each week is a good start. That equals about 500 milligrams of EPA/DHA each day. For treating disease, up to 4,000 milligrams per day is recommended by various studies, although values do vary. (96) It’s why a pescatarian diet can have such health protective effects.

In short, there is no single optimal EPA:DHA ratio. If we are really healthy, with an optimal omega-6 to omega-3 ratio (from a diet rich in omega-3 fatty acids and low in grains and vegetable oils) and have an active, stress-free lifestyle, relying on standard fish oil in the natural 1.5:1 EPA:DHA ratio or simply consuming oily fish is completely adequate.
Several recent clinical studies, especially those focusing on the benefits of omega-3 in inflammatory conditions, have investigated the actions of pure-EPA in protecting against excess inflammation in the body. EPA works in several different ways. Firstly, it is the precursor to a number of immune messengers, collectively called ‘eicosanoids’ (series-3 prostaglandins, series-3 thromboxanes and series-5 leukotrienes,) all of which have anti-inflammatory roles.

However, since the dosage of fish oil required for an ideal effect in the improvement of a patient is unknown, the Arthritis Center in the Department of Rheumatology at John Hopkins University considers including omega-3 fatty acids and fish oil in the treatment of arthritis as controversial. The University also cautions that arthritis patients must be wary of all the other side effects that can come from using fish oil. You can read more about arthritis on the web page of the Arthritis Foundation and the Arthritis Center.


Causing unsafe conditions. Fish oil may increase the risk of bleeding, which can lead to an unsafe condition. Excessive bleeding inside the body may also lead to conditions such as ulcers or liver disease which could be quite dangerous. Be aware of the signs and symptoms of this condition such as bruising easily or nosebleeds which could be a sign that you are developing this condition. If you begin to bleed more easily than usual then you should reduce the amount of fish oil you take regularly to reduce this condition.
Some high-quality omega-3 supplements will have lower amounts than EPA/DHA but accompany them with digestive enzymes. While it looks counterintuitive on a nutrition label, this is often done because there is debate about how much of the omega-3’s you actually absorb from supplements when taken alone. By coupling omega-3’s with a digestive enzyme blend, you are likely able to absorb more of the nutrient without having to consume as many grams.
Both omega−6 and omega−3 fatty acids are essential: humans must consume them in their diet. Omega−6 and omega−3 eighteen-carbon polyunsaturated fatty acids compete for the same metabolic enzymes, thus the omega−6:omega−3 ratio of ingested fatty acids has significant influence on the ratio and rate of production of eicosanoids, a group of hormones intimately involved in the body's inflammatory and homeostatic processes, which include the prostaglandins, leukotrienes, and thromboxanes, among others. Altering this ratio can change the body's metabolic and inflammatory state.[16] In general, grass-fed animals accumulate more omega−3 than do grain-fed animals, which accumulate relatively more omega−6.[86] Metabolites of omega−6 are more inflammatory (esp. arachidonic acid) than those of omega−3. This necessitates that omega−6 and omega−3 be consumed in a balanced proportion; healthy ratios of omega−6:omega−3, according to some authors, range from 1:1 to 1:4.[87] Other authors believe that a ratio of 4:1 (4 times as much omega−6 as omega−3) is already healthy.[88][89] Studies suggest the evolutionary human diet, rich in game animals, seafood, and other sources of omega−3, may have provided such a ratio.[90][91]
We are now fortunate to understand how these fats work in combination and in isolation, how they are digested, absorbed and utilised in the body, so we are able to tailor different blends of EPA and DHA according to the health benefits we are seeking to achieve. At Igennus, we have long specialised in the role of the omega-3 fatty acid EPA in clinical nutrition, as a powerful tool in the patient’s ‘toolkit’ for helping to regulate inflammation by restoring several biological markers, known as the omega-6 to omega-3 ratio and AA to EPA ratio. Before we discuss the therapeutic role of EPA in nutritional medicine, here’s a very brief summary of the role of both EPA and DHA in health throughout life.
In many cases, people are recommended to consume fish oil because it is an easy way to get additional omega-3 fatty acids into their diet. Omega-3 fats can be used to reduce swelling or to prevent blood clots which could cause major cardiovascular damage. There are many other conditions which can be decreased or improved with the use of fish oil. In most cases fish oil is used to help reduce high triglycerides which can cause serious conditions like diabetes or heart disease.
In fact, fish oil is even dipping its way into mainstream medicine. In September 2018, Amarin Corporation, the biopharmaceutical developer of pharmaceutical-grade fish oil Vascepa, released preliminary findings of its double-blind clinical trial. In the study, researchers tracked more than 8,000 adults for a median 4.9 years. The mix of study participants had either established cardiovascular disease or type 2 diabetes and another cardiovascular disease risk factor, along with persistently elevated triglycerides.
Full citation: Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KHO, AlAbdulghafoor FK, Summerbell CD, Worthington HV, Song F, Hooper L. Omega 3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2018, Issue 7. Art. No.: CD003177. DOI: 10.1002/14651858.CD003177.pub3.
Krill oil is a source of omega−3 fatty acids.[116] The effect of krill oil, at a lower dose of EPA + DHA (62.8%), was demonstrated to be similar to that of fish oil on blood lipid levels and markers of inflammation in healthy humans.[117] While not an endangered species, krill are a mainstay of the diets of many ocean-based species including whales, causing environmental and scientific concerns about their sustainability.[118][119][120]
What's more, ALA is just a precursor to EPA and DHA. You need certain enzymes to elongate and desaturate ALA so it can become long-chained omega-3s. Unfortunately, this does not work in some people, particularly those who are deficient in certain vitamins and minerals, leading to very low conversion rates – only 1 percent of ALA is converted to EPA/DHA. In some, the conversion can even dip as low as 0.1 to 0.5 percent!
^ 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.
Higher visual acuity after DHA supplementation is a consistent finding in infants born preterm. For infants born at term, the results are less consistent and are better explained by differences in sensitivity of the visual acuity test (electrophysiologic tests being more sensitive than subjective tests) or by differences in the amount of DHA included in the experimental formula.
Pay attention to the quality of fish oil when purchasing it. It is obtained from almost all fishes – fresh water, farm, ocean, deep sea and shallow sea fish. All these fishes can be contaminated with toxic compounds such as mercury, arsenic, lead, forms of calcium, furans, dioxins, PCBs, and methylmercury, and can negatively affect the human body. Therefore, the fish oil used must be pure. Many companies sell ultra refined or distilled fish oil, but you should always check if the standards have been followed and research on the company or the product before adding it to your diet.
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
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:
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)
Meanwhile, blood levels of DHA and EPA are very transitory, reflecting what an individual consumed only recently, while of course prostate cancer has a markedly longer progression. The study was not designed to isolate omega oil :: prostate cancer relationships, so conclusion would be weak. Seems likely to me that when faced with a serious disease, men suddenly begin to try living “right” in a hurry.

Respected health care organizations proposed intake recommendations for oily fish of two servings per week for healthy adults, which equates to approximately a daily total of 500 milligrams (mg) EPA and DHA.‡ The recommendation encourages adults already with or at-risk of developing cardiovascular disease to talk to their primary healthcare professional about supplementing with amounts greater than 500 mg of EPA and DHA per day. Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease.


The DART study, published in 1989, was the first randomized trial to show the efficacy of fish oil on CAD.37 In the trial, 2033 post-MI patients were randomized to receive 3 types of diets: a diet that was either high in cereal fiber, polyunsaturated fat, or fish oil. The fish oil group consumed 200 to 400 g/wk of fatty fish (2 portions of fish per week) or 0.5 g/d of Maxepa fish oil supplement. At 2 years, the primary end point of all-cause mortality was reduced by 29% in the fish oil group, whereas no improvement was seen in the other dietary advice groups.
"All these diseases have a common genesis in inflammation," says Joseph C. Maroon, MD, professor and vice chairman of the department of neurological surgery at the University of Pittsburgh School of Medicine. Co-author of Fish Oil: The Natural Anti-Inflammatory, Maroon says that in large enough amountsomega-3's reduce the inflammatory process that leads to many chronic conditions.

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.
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