Ramakrishnan, U., Stein, A. D., Parra-Cabrera, S., Wang, M., Imhoff-Kunsch, B., Juarez-Marquez, S., Rivera, J., and Martorell, R. Effects of docosahexaenoic acid supplementation during pregnancy on gestational age and size at birth: randomized, double-blind, placebo-controlled trial in Mexico. Food Nutr Bull 2010;31(2 Suppl):S108-S116. View abstract.
The most extensive data of the effect of fish oil on lipoprotein subfractions are based on trials performed before the widespread use of statins. This data were aggregated over a decade ago in a meta-analysis of 16 randomized trials including over 1500 patients.17 In this analysis, low-density lipoprotein (LDL) was increased by an average of 5% and high-density lipoprotein was marginally changed. Although a shift toward less atherogenic, larger and more buoyant LDL particle composition has been shown,74 this has been offset by the observation that the number of apolipoprotein B 100 particles increases and may be more susceptible to oxidation.75 Increased conversion of remnant particles (intermediate density lipoprotein) to LDL has also been observed.76
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.
Evidence suggests that omega−3 fatty acids modestly lower blood pressure (systolic and diastolic) in people with hypertension and in people with normal blood pressure.[25] Some evidence suggests that people with certain circulatory problems, such as varicose veins, may benefit from the consumption of EPA and DHA, which may stimulate blood circulation and increase the breakdown of fibrin, a protein involved in blood clotting and scar formation.[26][27] Omega−3 fatty acids reduce blood triglyceride levels but do not significantly change the level of LDL cholesterol or HDL cholesterol in the blood.[28][29] The American Heart Association position (2011) is that borderline elevated triglycerides, defined as 150–199 mg/dL, can be lowered by 0.5-1.0 grams of EPA and DHA per day; high triglycerides 200–499 mg/dL benefit from 1-2 g/day; and >500 mg/dL be treated under a physician's supervision with 2-4 g/day using a prescription product.[30]

Fish oil combined with fenofibrate has not been studied extensively in randomized controlled trials. Data to date, however, suggest that the combination is safe and effective.63,64 A recent randomized controlled trial of 100 patients with severe hypertriglyceridemia and HIV on highly active antiretroviral therapy showed that a regimen of fenofibrate and 3 g/d of fish oil for 8 weeks was well tolerated. The median baseline triglyceride level of 650 mg/dL was reduced by 65%.63 Another recent randomized, 2 month, double-blind, placebo-controlled trial, which was set up to assess the safety and efficacy of fenofibrate with 4 g of fish oil, showed that in the 81 patients assigned to combination therapy, triglyceride levels were reduced by 61%. Therapy was well-tolerated without significant adverse reactions at 8 weeks or at the end of a 2-year open label extension.64 The combination of fish oil and niacin requires further study.
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Secondary prevention fish oil studies demonstrate a significant reduction in MI. But unfortunately, both the observational and randomized trials were conducted in an era before the widespread use of HMG-CoA reductase inhibitors, and therefore, the incremental benefit is still unknown. Nevertheless, in patients receiving antiplatelet and anticoagulant therapy in addition to fish oil supplementation (even at doses as high as 4 g per day), no serious adverse complications have been reported.

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)
Increased consumption of omega 3 fats is widely promoted globally because of a common belief that that it will protect against heart disease. There is more than one possible mechanism for how they might help prevent heart disease, including reducing blood pressure or reducing cholesterol. Omega 3 fats are readily available as over-the-counter supplements and they are widely bought and used.

There have been conflicting results reported about EPA and DHA and their use with regard to major coronary events and their use after myocardial infarction. EPA+DHA has been associated with a reduced risk of recurrent coronary artery events and sudden cardiac death after an acute myocardial infarction (RR, 0.47; 95% CI: 0.219–0.995) and a reduction in heart failure events (adjusted HR: 0.92; 99% CI: 0.849–0.999) (34–36). A study using EPA supplementation in combination with a statin, compared with statin therapy alone, found that, after 5 y, the patients in the EPA group (n = 262) who had a history of coronary artery disease had a 19% relative reduction in major coronary events (P = 0.011). However, in patients with no history of coronary artery disease (n = 104), major coronary events were reduced by 18%, but this finding was not significant (37). This Japanese population already has a high relative intake of fish compared with other nations, and, thus, these data suggest that supplementation has cardiovascular benefits in those who already have sufficient baseline EPA+DHA levels. Another study compared patients with impaired glucose metabolism (n = 4565) with normoglycemic patients (n = 14,080). Impaired glucose metabolism patients had a significantly higher coronary artery disease HR (1.71 in the non-EPA group and 1.63 in the EPA group). The primary endpoint was any major coronary event including sudden cardiac death, myocardial infarction, and other nonfatal events. Treatment of impaired glucose metabolism patients with EPA showed a significantly lower major coronary event HR of 0.78 compared with the non–EPA-treated impaired glucose metabolism patients (95% CI: 0.60–0.998; P = 0.048), which demonstrates that EPA significantly suppresses major coronary events (38). When looking at the use of EPA+DHA and cardiovascular events after myocardial infarction, of 4837 patients, a major cardiovascular event occurred in 671 patients (13.9%) (39). A post hoc analysis of the data from these diabetic patients showed that rates of fatal coronary heart disease and arrhythmia-related events were lower among patients in the EPA+DHA group than among the placebo group (HR for fatal coronary heart disease: 0.51; 95% CI: 0.27–0.97; HR for arrhythmia-related events: 0.51; 95% CI: 0.24–1.11, not statistically significant) (39). Another study found that there was no significant difference in sudden cardiac death or total mortality between an EPA+DHA supplementation group and a control group in those patients treated after myocardial infarction (40). Although these last 2 studies appear to be negative in their results, it is possible that the more aggressive treatment with medications in these more recent studies could attribute to this.
The GISSI-Heart Failure trial was the first blinded, randomized trial to assess the efficacy of fish oil supplements in patients with heart failure.51 The trial enrolled 7046 subjects with heart failure; 60% with New York Heart Association class II symptoms and 40% with a history of MI. The majority of patients were on a standard heart failure regimen, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, and spironolactone, but only 22% were on a statin. At an average of 3.9 years, the coprimary end points of death and death or hospital admission for cardiovascular reasons were reduced by approximately 9% with fish oil supplementation. Sudden cardiac death, a secondary end-point, showed a statistically nonsignificant relative risk reduction of 7% with fish oil. There was also a reduction in 2 other arrhythmia-related secondary end-points: first hospitalization for ventricular arrhythmia and presumed arrhythmic death.
Boucher, O., Burden, M. J., Muckle, G., Saint-Amour, D., Ayotte, P., Dewailly, E. ... Jacobson, J. L.. (2011, May). Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age. American Journal of Clinical Nutrition 93(5), 1025-1037. Retrieved from http://ajcn.nutrition.org/content/93/5/1025.full
Fish oil has only a small benefit on the risk of premature birth.[43][44] A 2015 meta-analysis of the effect of omega−3 supplementation during pregnancy did not demonstrate a decrease in the rate of preterm birth or improve outcomes in women with singleton pregnancies with no prior preterm births.[45] A systematic review and meta-analysis published the same year reached the opposite conclusion, specifically, that omega−3 fatty acids were effective in "preventing early and any preterm delivery".[46]
^ Jump up to: a b c Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, Geleijnse JM, Rauch B, Ness A, Galan P, Chew EY, Bosch J, Collins R, Lewington S, Armitage J, Clarke R (March 2018). "Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals". JAMA Cardiology. 3 (3): 225–34. doi:10.1001/jamacardio.2017.5205. PMC 5885893. PMID 29387889.
Finally, in order for AA to be converted into inflammatory products it must be released from phospholipids (part of the cell membrane) using the enzyme phospholipase A2 and then converted by the enzyme cyclooxygenase. EPA utilises both of these enzymes, so if EPA levels are increased in the diet, it attracts enzyme away from AA to EPA – again giving rise to anti-inflammatory products instead of inflammatory ones.

In a 2009 joint study by the USDA and researchers at Clemson University in South Carolina, grass-fed beef was compared with grain-finished beef. The researchers found that grass-finished beef is higher in moisture content, 42.5% lower total lipid content, 54% lower in total fatty acids, 54% higher in beta-carotene, 288% higher in vitamin E (alpha-tocopherol), higher in the B-vitamins thiamin and riboflavin, higher in the minerals calcium, magnesium, and potassium, 193% higher in total omega−3s, 117% higher in CLA (cis-9, trans-11 octadecenoic acid, a cojugated linoleic acid, which is a potential cancer fighter), 90% higher in vaccenic acid (which can be transformed into CLA), lower in the saturated fats linked with heart disease, and has a healthier ratio of omega−6 to omega−3 fatty acids (1.65 vs 4.84). Protein and cholesterol content were equal.[86]
Our scientists also focused on each oil’s freshness, measured by the degree of oxidation. Oxidation occurs in two phases: primary (measured by peroxide values) and secondary (measured by p-anisidine values). Total oxidation is formalized into a quantitative score, TOTOX. While Labdoor conducted tests of both primary and secondary oxidation, advances in rancidity testing confirm that added flavors–particularly added citrus flavors prevalent in liquid formulations–skew p-anisidine values and result in false positive outcomes. Until analytical techniques measuring p-anisidine values that are able to account for added flavors are established, Labdoor will use peroxide values as the primary indicator of freshness. All products recorded measurable levels of oxidation, with the average product recording a peroxide values of 3.7 meq/kg. 14/51 products recorded peroxide levels at or above the upper limit (10 meq/kg).
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.
Special attention should also be given to the fact that most women have major deficiencies of omega-3. A 1991 study at the Mayo Clinic focused on 19 "normal" pregnant women consuming "normal diets," and it showed that all were deficient in omega-3 fats. Another study compared Inuit (Eskimo) women to Canadian women, and it revealed omega-3 deficiency in the milk of the Canadian nursing moms.
There are numerous omega-3 sources with varying proportions of EPA and DHA, and the balance of EPA and DHA in a supplement influences the actions of these fats in the body. For more information about the different types of omega-3 sources and which are most suited for your individual needs, read our page on the different types of omega-3 supplements
Ample evidence from animal studies supports regular supplementation with omega-3 oils as a means of lowering long-term cardiovascular risk. This may be due to omega-3 fatty acids’ effects on reducing inflammation, lowering triglycerides, reducing blood pressure, improving endothelial function, inducing new blood vessel formation after heart attack or stroke, and favorable modification of obesity-related inflammatory molecules.35-39
It exists in nature in three forms, one derived from land plants and two derived from marine sources. In the body, omega-3 is highly concentrated in the brain; it is critical to the formation and maintenance of nerve cell membranes. Research shows that in the nervous system, omega-3s foster the development of brain circuitry and the processing of information. They also play important roles in stabilizing mood and staving off cognitive decline. Low levels of omega-3s are linked to poor memory and depression. Omega-3 fats are also critical for the formation of anti-inflammatory molecules in the body.
There’s more good news when it comes to fish oil and eye health, and it’s just not just for diabetic this time. Fish oil has been shown to reverse age-related eye disorders. In March 2014, French researchers evaluated 290 patients with age-related macular degeneration (AMD), and they discovered that dietary oil fish and seafood intake were significantly lower in AMD patients. Due to the high EPA and DHA levels in fish oil, it was concluded that this kind of nutritional intervention could especially benefit those at high risk for neovascular age-related macular degeneration. (24)
Ample evidence from animal studies supports regular supplementation with omega-3 oils as a means of lowering long-term cardiovascular risk. This may be due to omega-3 fatty acids’ effects on reducing inflammation, lowering triglycerides, reducing blood pressure, improving endothelial function, inducing new blood vessel formation after heart attack or stroke, and favorable modification of obesity-related inflammatory molecules.35-39
There is, however, significant difficulty in interpreting the literature due to participant recall and systematic differences in diets.[53] There is also controversy as to the efficacy of omega−3, with many meta-analysis papers finding heterogeneity among results which can be explained mostly by publication bias.[54][55] A significant correlation between shorter treatment trials was associated with increased omega−3 efficacy for treating depressed symptoms further implicating bias in publication.[55]
Fish oil has only a small benefit on the risk of premature birth.[43][44] A 2015 meta-analysis of the effect of omega−3 supplementation during pregnancy did not demonstrate a decrease in the rate of preterm birth or improve outcomes in women with singleton pregnancies with no prior preterm births.[45] A systematic review and meta-analysis published the same year reached the opposite conclusion, specifically, that omega−3 fatty acids were effective in "preventing early and any preterm delivery".[46]
The hypotriglyceridemic effect of fish oil is well established and is related to both dose and baseline triglyceride level. Patients with triglycerides <90 mg/dL will be negligibly affected unless very high doses of omega-3 FA are used.67,68 However, in patients with triglycerides >200 mg/dL, who are treated with 4 g/d of fish oil, a 30% reduction in triglycerides is expected.17,69 For patients with triglycerides >500 mg/dL who are at risk for pancreatitis, the National Cholesterol Education Program Adult Treatment Panel III guidelines recommend using fish oil supplements as an adjunctive therapy to fibrates and nicotinic acid.70 Lovaza capsules have been shown to be effective, safe, and comparable to gemfibrozil in treating triglycerides at this range.71,72 The official label recommendation for Lovaza is for patients with triglycerides >500 mg/dL.73
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.
Attention deficit-hyperactivity disorder (ADHD) in children. Early research shows that taking fish oil improves attention, mental function, and behavior in children 8-13 years-old with ADHD. Other research shows that taking a specific supplement containing fish oil and evening primrose oil (Eye Q, Novasel) improves mental function and behavior in children 7-12 years-old with ADHD.
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