Eicosatetraenoic Acid (ETA): ETA is a lesser-known omega-3 fatty acid that also contains 20 carbons, like EPA, but only four bonds instead of five. It is found richly inroe oil and green-lipped mussel and is only recently being recognized for its potent health benefits. Not only is it anti-inflammatory, like the other omega-3s, but ETA can also limit your body’s production of the inflammatory omega-6 fatty acid arachidonic acid (ARA). In fact, ETA redirects the enzyme that normally creates ARA to convert it to EPA instead!
Hamazaki, K., Syafruddin, D., Tunru, I. S., Azwir, M. F., Asih, P. B., Sawazaki, S., and Hamazaki, T. The effects of docosahexaenoic acid-rich fish oil on behavior, school attendance rate and malaria infection in school children--a double-blind, randomized, placebo-controlled trial in Lampung, Indonesia. Asia Pac.J Clin Nutr 2008;17(2):258-263. View abstract.
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.

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.


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]
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]
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.

The number, location, and orientation of the double bonds determine the health effects of fatty acids on the body. One aspect of this is their effect on triglycerides and LDL and HDL types of cholesterol, which in turn affect how much cholesterol gets deposited on the inside of blood vessels. There are also subtypes of LDL and HDL which are also likely important to their health effects.
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.

A Cochrane meta-analysis published in June 2012 found no significant protective effect for cognitive decline for those aged 60 and over and who started taking fatty acids after this age. A co-author of the study said to Time, "Our analysis suggests that there is currently no evidence that omega-3 fatty acid supplements provide a benefit for memory or concentration in later life".[43]
Jump up ^ Talakoub, Lily; Neuhaus, Isaac M.; Yu, Siegrid S. (2008). "Chapter 2: Cosmoceuticals". In Alam, Murad; Gladstone, Hayes B.; Tung, Rebecca. Cosmetic Dermatology. Requisites in dermatology. Elsevier Health Sciences. p. 9. ISBN 9780702031434. Retrieved 2014-10-23. Other oils used as emollients include fish oil, petrolatum, shea butter, and sunflower seed oil.
The FDA product label on Lovaza warns of potential bleeding complications with the coadministration of anticoagulants. This warning is based on observational studies that suggested a prolonged bleeding time in populations ingesting high levels of fish oil77 and on in vitro studies that demonstrated an effect on pro-thrombotic mediators such as a reduction in thromboxane A2 production78 and platelet activation factor.79 The same trend, however, has not been clearly demonstrated in measurements of clotting times or in factors of fibrinolysis.80 In addition, in randomized clinical trials of patients undergoing coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, endarterectomy and diagnostic angiography, no adverse bleeding related events have been demonstrated.81 For example, in a trial of 500 patients randomized to pretreatment with 6.9 g of DHA and EPA preparation 2 weeks before balloon percutaneous transluminal coronary angioplasty (where all the patients received 325 mg/d of aspirin and heparin bolus periprocedure), no difference was seen in bleeding complications.82 Similar results were seen in a trial of 610 patients undergoing coronary artery bypass graft surgery, randomized to either placebo or 4 g/d of fish oil and then further randomized to aspirin or warfarin (dosed to an international normalized ratio [INR] goal of 2.5–4.2). At 1 year, the number of bleeding complications was not increased.15 The effect of fish oil on INR values has not been studied extensively, but a small, randomized trial showed that fish oil did not alter the Coumadin dosing regimen.83 There is very little evidence that a lower target INR is necessary in patients receiving chronic warfarin therapy and fish oil.
Hernandez, D., Guerra, R., Milena, A., Torres, A., Garcia, S., Garcia, C., Abreu, P., Gonzalez, A., Gomez, M. A., Rufino, M., Gonzalez-Posada, J., Lorenzo, V., and Salido, E. Dietary fish oil does not influence acute rejection rate and graft survival after renal transplantation: a randomized placebo-controlled study. Nephrol.Dial.Transplant. 2002;17(5):897-904. View abstract.

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 ^ Talakoub, Lily; Neuhaus, Isaac M.; Yu, Siegrid S. (2008). "Chapter 2: Cosmoceuticals". In Alam, Murad; Gladstone, Hayes B.; Tung, Rebecca. Cosmetic Dermatology. Requisites in dermatology. Elsevier Health Sciences. p. 9. ISBN 9780702031434. Retrieved 2014-10-23. Other oils used as emollients include fish oil, petrolatum, shea butter, and sunflower seed oil.
Jump up ^ Martins, Julian G (2009). "EPA but Not DHA Appears to Be Responsible for the Efficacy of Omega-3 Long Chain Polyunsaturated Fatty Acid Supplementation in Depression: Evidence from a Meta-Analysis of Randomized Controlled Trials". Journal of the American College of Nutrition. 28 (5): 525–42. doi:10.1080/07315724.2009.10719785. PMID 20439549.
Irish AB, Viecelli AK, Hawley CM, et al; Omega-3 Fatty Acids (Fish Oils) and Aspirin in Vascular Access Outcomes in Renal Disease (FAVOURED) Study Collaborative Group. Effect of fish oil supplementation and aspirin use on arteriovenous fistula failure in patients requiring hemodialysis: A randomized clinical trial. JAMA Intern Med. 2017;177(2):184-193. View abstract.
Research conducted at the Louisiana State University has shown that fatty acids are effective in treating Alzheimer’s disease. Since fish oil is one of the best sources of essential fatty acids, including EPA and DHA, it helps in the treatment of Alzheimer’s disease. More research conducted at the University of California in Los Angeles (UCLA) validates the usefulness of fish oil as a possible remedy for the disease. The Alzheimer’s Association recommends fish containing a higher content of omega-3 fatty acids to patients since it acts as a defense against Alzheimer’s disease and dementia.
However, this difference in the length of the carbon chain gives these two types of omega-3s significant characteristics. EPA and DHA are long-chain fatty acids, while ALA is a short-chain fatty acid. The long-chain fatty acids are more important for cellular health. Another omega-3 fat, docosapentaenoic acid (DPA) can also be better synthesized by your body by elongating EPA.

Fish oil’s most potent effect on atherosclerosis may be related to its potential to alter plaque inflammation, thereby stabilizing vulnerable plaques. In recent years there has been a growing body of evidence that is shifting the paradigm of how inflammation is contained and dissipated.4 In this new model, inflammation resolution is an active process mediated by lipid-derived compounds. Newly discovered families of chemical mediators, resolvins, and protectins5,6 are directly involved in blocking neutrophil migration, infiltration, and recruitment, as well as in blocking T-cell migration and promoting T-cell apoptosis.7–12 In addition, protectins can reduce tumor necrosis factor and interferon secretion.13 Interestingly, both protectins and resolvins are strictly derived from omega-3 FA. EPA is the substrate of the resolvins family and DHA can be converted to both resolvins and protectins.7 It may be that the effects of fish oil on inflammatory mediators underlie the positive findings demonstrated in several trials assessing fish oil and plaque stability.14–16


Fish and omega-3 fatty acids. If you keep up with the latest nutrition news, you may have a pretty good sense of what they offer. But, if you're like many people, you still can't tell your omega-3s from your omega-6s -- and you sure as heck can't pronounce eicosapentaenoic acid. That's OK. Our fishing expedition turned up some interesting facts to share about omega-3 fatty acids and fish.
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]
Anxiety, the most commonly experienced psychiatric symptom, is a psychological state derived from inappropriate or exaggerated fear leading to distress or impairment. The lifetime prevalence of any anxiety disorder is reported to be approximately 1 in 3.1 Anxiety is often comorbid with depressive disorders2 and is associated with lower health-related quality of life3 and increased risk of all-cause mortality.4 Treatment options include psychological treatments, such as cognitive-behavioral therapy and pharmacological treatments, mainly with selective serotonin reuptake inhibitors.5 Individuals with anxiety and related disorders tend to be more concerned about the potential adverse effects of pharmacological treatments (eg, sedation or drug dependence) and may be reluctant to engage in psychological treatments that can be time-consuming and costly, as well as sometimes limited in availability.6 Thus, evidence-based and safer treatments are required, especially for anxious patients with comorbid medical conditions.
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.
Another study conducted by researchers at Rhode Island Hospital examined the relationship between fish oil supplementation and indicators of cognitive decline. The subjects of the study were older adults: 229 cognitively normal individuals, 397 patients with mild cognitive impairment and 193 patients with Alzheimer’s disease. They were assessed with neuropsychological tests and brain magnetic resonance imaging every six months while taking fish oil supplements. The study found that the adults taking fish oil (who had not yet developed Alzheimer’s and did not have genetic risk factor for developing Alzheimer’s known as APOE ε4) experienced significantly less cognitive decline and brain shrinkage than adults not taking fish oil. (9)
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.

Findings  In this systematic review and meta-analysis of 19 clinical trials including 2240 participants from 11 countries, improvement in anxiety symptoms was associated with omega-3 polyunsaturated fatty acid treatment compared with controls in both placebo-controlled and non–placebo-controlled trials. The anxiolytic effects of omega-3 polyunsaturated fatty acids were also stronger in participants with clinical conditions than in subclinical populations.
Most brands of fish oil have been proven safe, free of detectable traces of mercury, and do not contain unsafe levels of PCBs (polychlorinated biphenyls), a toxin and pollutant believed to pose various health threats. To avoid contaminants in an unrefined supplement, it's best to choose a fish-oil supplement made from small, oily fish like anchovy, sardines or menhaden.

Bo and I worked with Dr. Harris many years ago to measure the impact of eating one Omega Cookie® daily on the study participants’ omega-3 index levels, and we recently ran into him at ISFFAL. At the conference, we remeasured our omega-3 index and omega-6/omega-3 ratios, and a few weeks later, we got our results in the mail. For the two of us, it was exciting to get another concrete measure of how our daily omega-3 consumption impacted our scores. For the record, we take one vial of Omega Restore™ per night and frequently sneak an Omega Heaven® or Omega Cookie during the day.

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.


It is well known that fish oil has the ability to improve vision. It also helps in avoiding age-related macular degeneration. The National Eye Institute at the National Institute of Health in the United States plans to conduct a nationwide study to evaluate the effect of fish oil in treating macular degeneration. This study will provide strong scientific evidence regarding the benefits of fish oil for eye care, thereby allowing government agencies and physicians to strongly recommend fish oil for macular degeneration.

The most widely available dietary source of EPA and DHA is cold-water oily fish, such as salmon, herring, mackerel, anchovies, and sardines. Oils from these fish have a profile of around seven times as much omega-3 oils as omega-6 oils. Other oily fish, such as tuna, also contain omega-3 in somewhat lesser amounts. Although fish is a dietary source of omega-3 oils, fish do not synthesize them; they obtain them from the algae (microalgae in particular) or plankton in their diets.[22]
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.
Docosahexaenoic acid (DHA) found primarily in fish oil, this is the ultimate form of fatty acid in humans. Most people get far too little of this all-important fatty acid, especially since the conversion of ALA to DHA is slow and minimally yielding. Getting a daily dose of of DHA (600 to 1000 mg) from supplements is preferable to reap the health benefits. You have a choice of taking a fish oil supplement or one derived from algae or krill, a shrimp-like crustacean.

Omega-3 [(n-3)] fatty acids have been linked to healthy aging throughout life. Recently, fish-derived omega-3 fatty acids EPA and DHA have been associated with fetal development, cardiovascular function, and Alzheimer's disease. However, because our bodies do not efficiently produce some omega-3 fatty acids from marine sources, it is necessary to obtain adequate amounts through fish and fish-oil products. Studies have shown that EPA and DHA are important for proper fetal development, including neuronal, retinal, and immune function. EPA and DHA may affect many aspects of cardiovascular function including inflammation, peripheral artery disease, major coronary events, and anticoagulation. EPA and DHA have been linked to promising results in prevention, weight management, and cognitive function in those with very mild Alzheimer's disease.
An animal study involving the omega-3 ETA discovered that subjects experienced a drop in overall inflammation similar to that caused by NSAIDs (non-steroidal anti-inflammatory drugs), but without the dangerous gastrointestinal side effects. The study authors also pointed out that eicosapentaenoic acid seems to be even more potent than the conventional omega-3s found in fish oil supplements (EPA/DHA). (56)

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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