Heart disease. Eating fish can be effective for keeping people with healthy hearts free of heart disease. People who already have heart disease might also be able to lower their risk of dying from heart disease by eating fish. The picture is less clear for fish oil supplements. For people who already take heart medications such as a "statin" and those who already eat a decent amount of fish, adding on fish oil might not offer any additional benefit.
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 way that fish oil does that is to interfere with carbohydrate metabolism, and in insulin-resistant people or in people with specific genetic differences that might predispose them to having very high triglycerides, you do benefit from interfering that pathway with the fish oil, but I would actually try a low-carbohydrate diet in a lot of those situations to see if that helps with lowering triglycerides, or in the case of insulin resistance, I would try to address the insulin resistance at its root cause.
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.
As with other supplements, when it comes to quality, you get what you pay for. Life Time sources its omega-3 fish oil (both capsules and liquid) from sustainable fisheries off the coast of Chile. We only use oils from small, cold-water anchovy, sardine, and mackerel. It’s molecularly distilled to be sure it’s free of mercury, PCBs, and heavy metals. If your fish oil brand doesn’t name the species of fish it’s sourced from, or it lists larger, predatory species, the quality and purity of the oil could be less than optimal.
Stiefel, P., Ruiz-Gutierrez, V., Gajon, E., Acosta, D., Garcia-Donas, M. A., Madrazo, J., Villar, J., and Carneado, J. Sodium transport kinetics, cell membrane lipid composition, neural conduction and metabolic control in type 1 diabetic patients. Changes after a low-dose n-3 fatty acid dietary intervention. Ann Nutr Metab 1999;43(2):113-120. View abstract.
First, all Omega-3 products are not alike. Here's what I learned about Omega-3 from my research. The "3" relates to three sources of Omega-3 fatty acids. Two of them, DHA and EPA are found in marine products such as fish and krill. The third source, ALA, is from plants. So with fish oil you are getting two of the three sources at once. That makes sense to me as a good reason to take Omega-3 fish oil. You will also note below that many of the reasons we choose to take Omega-3 do not occur with plant-based products.
Humans can convert short-chain omega−3 fatty acids to long-chain forms (EPA, DHA) with an efficiency below 5%.[73][74] The omega−3 conversion efficiency is greater in women than in men, but less studied.[75] Higher ALA and DHA values found in plasma phospholipids of women may be due to the higher activity of desaturases, especially that of delta-6-desaturase.[76]
For those who do not eat seafood, another way exists for you to get a healthy dose of EPA and DHA each day. Fish oil supplements, which are rich in EPA and DHA, can be made from a variety of fish, with the most common ones being halibut, tuna, salmon, cod liver, mackerel and herring. On average, one 3.5 ounce serving of fatty fish contains about 1 gram of omega-3s, which can be obtained through fish oil supplements, according to MedlinePlus.
In comparison, the omega-3s found in krill appear to be more rapidly incorporated into red blood cell phospholipids.7 This is important, because not only do scientists view the uptake of essential fatty acids in red blood cells as a biomarker for uptake into the brain,8 but additional research suggests that when omega-3 fatty acids such as DHA are bound to phospholipids as they are with krill, it increases their uptake to the brain.9 This is further supported by human clinical research, which suggests ingestion of phospholipid-bound EPA and DHA increase cognitive function scores to a greater degree compared with scores obtained when the fatty acids in the ingested oil were provided in the triglycerides storage form.10
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.

The evidence linking the consumption of marine omega−3 fats to a lower risk of cancer is poor.[8][13] With the possible exception of breast cancer,[8][14][15] there is insufficient evidence that supplementation with omega−3 fatty acids has an effect on different cancers.[5][16] The effect of consumption on prostate cancer is not conclusive.[8][15] There is a decreased risk with higher blood levels of DPA, but an increased risk of more aggressive prostate cancer was shown with higher blood levels of combined EPA and DHA.[17] In people with advanced cancer and cachexia, omega−3 fatty acids supplements may be of benefit, improving appetite, weight, and quality of life.[18]
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.
In general, most health organizations agree 250–500 milligrams of EPA and DHA combined each day is a reasonable amount to support healthy individuals. However, people with heart problems (or those with a high risk of heart disease), depression, anxiety and cancer (and possibly more conditions) may benefit from higher doses — up to 4,000 milligrams per day for some heart-related conditions. (5)
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.
The ultimate goal of using omega-3 fatty acids is the reduction of cellular inflammation. Since eicosanoids derived from arachidonic acid (AA), an omega-6 fatty acid, are the primary mediators of cellular inflammation, EPA becomes the most important of the omega-3 fatty acids to reduce cellular inflammation for a number of reasons. First, EPA is an inhibitor of the enzyme delta-5-desaturase (D5D) that produces AA (1). The more EPA you have in the diet, the less AA you produce. This essentially chokes off the supply of AA necessary for the production of pro-inflammatory eicosanoids (prostaglandins, thromboxanes, leukotrienes, etc.). DHA is not an inhibitor of this enzyme because it can’t fit into the active catalytic site of the enzyme due to its larger spatial size. As an additional insurance policy, EPA also competes with AA for the enzyme phospholipase A2 necessary to release AA from the membrane phospholipids (where it is stored). Inhibition of this enzyme is the mechanism of action used by corticosteroids. If you have adequate levels of EPA to compete with AA (i.e. a low AA/EPA ratio), you can realize many of the benefits of corticosteroids but without their side effects. That’s because if you don’t release AA from the cell membrane then you can’t make inflammatory eicosanoids. Because of its increased spatial dimensions, DHA is not a good competitor of phospholipase A2 relative to EPA. On the other hand, EPA and AA are very similar spatially so they are in constant competition for the phospholipase A2 enzyme just as both fatty acids are in constant competition for the delta-5 desaturase enzyme. This is why measuring the AA/EPA ratio is such a powerful predictor of the state of cellular inflammation in your body.
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.
The human body can make most of the types of fats it needs from other fats or raw materials. That isn’t the case for omega-3 fatty acids (also called omega-3 fats and n-3 fats). These are essential fats—the body can’t make them from scratch but must get them from food. Foods high in Omega-3 include fish, vegetable oils, nuts (especially walnuts), flax seeds, flaxseed oil, and leafy vegetables.
Between the ages of five and 65, the majority of the body’s needs can be met by using EPA-rich oils and eating fish, marine products, organic greens and pastured animal products. EPA levels are under constant demand and low EPA levels in adolescents and adults correlates strongly with development of mental health issues, including depression, dyslexia and dyspraxia, heart problems, joint and bone conditions, as well as neurodegenerative diseases such as MS and Parkinson’s. EPA also protects our genes and cell cycle, as well as helping to keep our stress response regulated, so an adequate supply of EPA throughout adult life can help prevent a range of chronic illness.
A report by the Harvard Medical School studied five popular brands of fish oil, including Nordic Ultimate, Kirkland and CVS. They found that the brands had "negligible amounts of mercury, suggesting either that mercury is removed during the manufacturing of purified fish oil or that the fish sources used in these commercial preparations are relatively mercury-free".[66]
Fish oil supplement studies have failed to support claims of preventing heart attacks or strokes.[3][4][5][6] Earlier, in 2007, the American Heart Association had recommended the consumption of 1 gram of fish oil daily, preferably by eating fish, for patients with coronary artery disease, but cautioned pregnant and nursing women to avoid eating fish with high potential for mercury contaminants including mackerel, shark, and swordfish.[32] (Optimal dosage was related to body weight.)
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.
Due to the presence of Omega-3 fatty acids, fish oil has been promoted for relieving depression, sadness, anxiety, restlessness, mental fatigue, stress, decreased sexual desire, suicidal tendencies, and other nervous disorders. Researchers at the Case Western Reserve University School of Medicine in Cleveland, Ohio, in their research publication titled “Fish Oils and Bipolar Disorder: A Promising but Untested Treatment”, state that fish oil can be useful in mood stabilization and the treatment of bipolar disorders. It is unsurprising, therefore, that countries where fish is frequently eaten, have a low incidence of depression. Similarly, research conducted on prisoners has shown that when prisoners were given seafood containing a higher amount of omega-3 fatty acids, there was a significant drop in the homicide rate and the frequency of violence. Intake of fish is also a good remedy for depression. Findings of a research study suggest that fish consumption may be beneficial for women’s mental health and reduces the risk of developing depression in women.
Capanni, M., Calella, F., Biagini, M. R., Genise, S., Raimondi, L., Bedogni, G., Svegliati-Baroni, G., Sofi, F., Milani, S., Abbate, R., Surrenti, C., and Casini, A. Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study. Aliment.Pharmacol.Ther. 4-15-2006;23(8):1143-1151. View abstract.
Egert, S., Somoza, V., Kannenberg, F., Fobker, M., Krome, K., Erbersdobler, H. F., and Wahrburg, U. Influence of three rapeseed oil-rich diets, fortified with alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid on the composition and oxidizability of low-density lipoproteins: results of a controlled study in healthy volunteers. Eur J Clin Nutr 2007;61(3):314-325. View abstract.
Heterogeneity was examined using the Q statistic and the corresponding P values,41 and the I2 statistic was used to evaluate the proportion of variation resulting from among-study differences. Any possible publication bias was detected with both funnel plots and Egger regression in the main part of the meta-analysis.42 By using Duval and Tweedie’s trim-and-fill test, we adjusted the effect sizes for potential publication bias if there was evidence of publication bias detected by this test in the Comprehensive Meta-analysis statistical software, version 3.43 To investigate the potential confounding effects of any outliers within the recruited studies, sensitivity testing was conducted with the 1-study removal method to detect the potential outliers.44
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]
Omega-3 [(n-3)] long-chain PUFA, including EPA and DHA, are dietary fats with an array of health benefits (1). They are incorporated in many parts of the body including cell membranes (2) and play a role in antiinflammatory processes and in the viscosity of cell membranes (3, 4). EPA and DHA are essential for proper fetal development and healthy aging (5). DHA is a key component of all cell membranes and is found in abundance in the brain and retina (6). EPA and DHA are also the precursors of several metabolites that are potent lipid mediators, considered by many investigators to be beneficial in the prevention or treatment of several diseases (7).
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.
Several other analyses of the evidence have been done in the last few years (2012 or later), and like the 2018 analysis and the AHRQ report, most found little or no evidence for a protective effect of omega-3 supplements against heart disease. However, some earlier analyses suggested that omega-3s could be helpful. The difference between the newer conclusions and the older ones may reflect two changes over time: 

In 1964 it was discovered that enzymes found in sheep tissues convert omega−6 arachidonic acid into the inflammatory agent called prostaglandin E2[71] which both causes the sensation of pain and expedites healing and immune response in traumatized and infected tissues.[72] By 1979 more of what are now known as eicosanoids were discovered: thromboxanes, prostacyclins, and the leukotrienes.[72] The eicosanoids, which have important biological functions, typically have a short active lifetime in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. If the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may, however, have deleterious effects.[72] Researchers found that certain omega−3 fatty acids are also converted into eicosanoids, but at a much slower rate. Eicosanoids made from omega−3 fatty acids are often referred to as anti-inflammatory, but in fact they are just less inflammatory than those made from omega−6 fats. If both omega−3 and omega−6 fatty acids are present, they will "compete" to be transformed,[72] so the ratio of long-chain omega−3:omega−6 fatty acids directly affects the type of eicosanoids that are produced.[72]
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.
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.
Some research indicates that people who eat more seafood may have a reduced risk of cognitive decline. However, omega-3 supplements haven’t been shown to help prevent cognitive impairment or Alzheimer’s disease or to improve symptoms of these conditions. For example, a large NIH-sponsored study completed in 2015 indicated that taking EPA and DHA supplements did not slow cognitive decline in older adults. The people studied were participants in a larger eye disease study, and all of them had age-related macular degeneration (AMD). 

Henriksen, C., Haugholt, K., Lindgren, M., Aurvag, A. K., Ronnestad, A., Gronn, M., Solberg, R., Moen, A., Nakstad, B., Berge, R. K., Smith, L., Iversen, P. O., and Drevon, C. A. Improved cognitive development among preterm infants attributable to early supplementation of human milk with docosahexaenoic acid and arachidonic acid. Pediatrics 2008;121(6):1137-1145. View abstract.
The Lyon Diet Heart Study, performed shortly after the DART study, was a prospective trial of 607 survivors of MI who were randomized to either a Mediterranean diet or a regular Western diet.49 At a mean follow-up of 27 months, the primary end point of death from cardiovascular causes and nonfatal deaths had a 73% relative risk reduction—a positive effect that continued at follow up assessment at a mean of 46 months.50 FA analysis of plasma lipids showed that in the patients randomized to a Mediterranean diet, there was a higher concentration of alpha-linolenic acid as well as EPA. Fish, however, was consumed in similar amounts by both the Western and Mediterranean diet groups. The higher blood level of EPA in the Mediterranean diet arm was attributed to its synthesis from alpha-linolenic acid, which was 60-times higher than the plasma concentration of EPA. In addition, the risk reduction that occurred in this trial could not be attributed to one particular diet intervention because as the consumption of fruits and vegetables increased, the consumption of monounsaturated fat increased, while saturated fat and cholesterol were decreased.

Rogers, P. J., Appleton, K. M., Kessler, D., Peters, T. J., Gunnell, D., Hayward, R. C., Heatherley, S. V., Christian, L. M., McNaughton, S. A., and Ness, A. R. No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial. Br J Nutr 2008;99(2):421-431. View abstract.
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