• Fish oil – Fish oil is among the primary ways that people enhance their intake of omega-3 fats. High-quality fish oils can certainly provide many health benefits. However, this oil is weak in antioxidants. This means that as you increase your omega-3 intake through fish oil consumption, you actually increase your need for added antioxidant protection.
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.

Sekikawa, A., Curb, D., Ueshima, H., El-Saed, A., Kadowaki, T., Abbott, R. D., ... Kuller, L. H. (2008 August 5). Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese Americans, and Whites: a cross-sectional study. Journal of the American College of Cardiology 52(6), 417–424. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736602/
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Humans are unable to place double bonds beyond position 9 on long chain polyunsaturated fatty acids (FA), making the omega-3 FA synthesized in plants and in marine microalgae essential elements to the human diet.1 Fish contain high levels of 2 omega-3 FA, eicosapentaenoic acid (EPA; C20:5 n-3), and docosahexaenoic acid [DHA]; C22:6 n-3)2,3 (Fig. 1). Many claims about the role of these omega-3 FA have been made in the prevention and treatment of cardiovascular disease. For instance, fish oil is seen as having a therapeutic role in coronary artery disease (CAD), heart failure, fatal and nonfatal arrhythmias, as well as offering an alternative or adjunct to the standard therapy for hypertriglyceridemia and diabetes. This review will highlight the potential mechanisms of fish oil on cardiovascular disease and provide an update of clinical trial results. The established uses in the treatment of hypertriglyceridemia and sources of omega-3 FA—both dietary and drug therapy—will be iterated, along with its potential application in combination with standard hypolipidemic agents. Finally, the limitations of current data will be addressed, as well as suggested recommendations for clinical use.
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
Fish oil is effective in reducing inflammation in the blood and tissues. Regular consumption of fish oil supplements, tablets, pills, and capsules is helpful to those who suffer from chronic inflammatory diseases. Fish oil is effective in treating gastrointestinal disorders, Celiac disease, short bowel syndrome and inflammatory bowel disease (IBD) including Crohn’s Disease and ulcerative colitis, which are both typical disorders of the intestine. Patients suffering from Crohn’s disease often find it difficult to absorb vitamins, fats, and essential supplements. Fish oil supplements are an effective diet for such patients.
The National Institutes of Health (NIH) has created a website, NIH Clinical Research Trials and You, to help people learn about clinical trials, why they matter, and how to participate. The site includes questions and answers about clinical trials, guidance on how to find clinical trials through ClinicalTrials.gov and other resources, and stories about the personal experiences of clinical trial participants. Clinical trials are necessary to find better ways to prevent, diagnose, and treat diseases.

Children: Fish oil is POSSIBLY SAFE when taken by mouth appropriately. Fish oil has been used safely through feeding tubes in infants for up to 9 months. But young children should not eat more than two ounces of fish per week. Fish oil is POSSIBLY UNSAFE when consumed from dietary sources in large amounts. Fatty fish contain toxins such as mercury. Eating contaminated fish frequently can cause brain damage, mental retardation, blindness and seizures in children.
You “beat me to the punch.” despite labels, cured meats , aged fats, as well as those heated to a high enough temperature all have trans bonds. Fish that offer high amounts of Omega-3 also often are high in mercury. I was fortunate to have a very good teacher for experimental design. One should be careful to assume that a study actually measures what it claims to and without “confounders” Confounders are parts of the study that complicate the the “logic” of the design. Also, were other fat contents measured or controlled? It would be reasonable to suspect that those with higher levels of Omega-3 could have higher levels of Omega-6, fats in general , High levels of protein, higher levels of testosterone, or lower levels of certain hormones. In addition, statistical studies do not and have never indicated a causal relationship. I have a fear of how much we have begun to rely on statistical correlational studies which are at the end of the day”soft” science.
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)

In another study, Australian researchers looked at whether giving infants added omega-3 fatty acids might improve health,4 including reducing their risk for heart disease. They gave 420 infants either an omega 3 supplement or olive oil from birth through six months, then revisited that at age 5 years to see if either group appeared healthier from a heart risk point of view.
Children: Fish oil is POSSIBLY SAFE when taken by mouth appropriately. Fish oil has been used safely through feeding tubes in infants for up to 9 months. But young children should not eat more than two ounces of fish per week. Fish oil is POSSIBLY UNSAFE when consumed from dietary sources in large amounts. Fatty fish contain toxins such as mercury. Eating contaminated fish frequently can cause brain damage, mental retardation, blindness and seizures in children.

It’s uncertain whether omega-3 fatty acid supplements are helpful for depression. Although some studies have had promising results, a 2015 evaluation of 26 studies that included more than 1,400 people concluded that if there is an effect, it may be too small to be meaningful. Other analyses have suggested that if omega-3s do have an effect, EPA may be more beneficial than DHA and that omega-3s may best be used in addition to antidepressant medication rather than in place of it. 
The omega-3 index is also important because it is inversely related to one’s omega-6 to omega-3 ratio — another important measurement (3). A lower omega-6/omega-3 ratio (meaning, you consume a balanced amount of these two fatty acid families) is associated with a reduced risk of many chronic diseases, including cardiovascular disease, cancer, and autoimmune disease, to name a few (4). Of course, most people get far too much omega-6 and too little omega-3, thanks to the plethora of highly processed foods in the Western diet.

“This idea has since been pretty discredited; we really don’t know if the Eskimos got heart disease or not,” said Malden C. Nesheim, emeritus professor of nutrition at Cornell University, who chaired an Institute of Medicine committee assessing the risks and benefits of seafood in the early 2000s. “I’ve been an omega-3 skeptic since doing this study.”


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.

Increasing ALA intake probably makes little or no difference to all‐cause mortality (RR 1.01, 95% CI 0.84 to 1.20, 19,327 participants; 459 deaths, 5 RCTs),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25, 18,619 participants; 219 cardiovascular deaths, 4 RCTs), and it may make little or no difference to CHD events (RR 1.00, 95% CI 0.80 to 1.22, 19,061 participants, 397 CHD events, 4 RCTs, low‐quality evidence). However, increased ALA may slightly reduce risk of cardiovascular events (from 4.8% to 4.7%, RR 0.95, 95% CI 0.83 to 1.07, 19,327 participants; 884 CVD events, 5 RCTs, low‐quality evidence), and probably reduces risk of CHD mortality (1.1% to 1.0%, RR 0.95, 95% CI 0.72 to 1.26, 18,353 participants; 193 CHD deaths, 3 RCTs), and arrhythmia (3.3% to 2.6%, RR 0.79, 95% CI 0.57 to 1.10, 4,837 participants; 141 events, 1 RCT). Effects on stroke are unclear.


The systematic review suggests that eating more ALA through food or supplements probably has little or no effect on cardiovascular deaths or deaths from any cause. However, eating more ALA probably reduces the risk of heart irregularities from 3.3 to 2.6%. The review team found that reductions in cardiovascular events with ALA were so small that about 1000 people would need to increase consumption of ALA for one of them to benefit. Similar results were found for cardiovascular death. They did not find enough data from the studies to be able to measure the risk of bleeding or blood clots from using ALA.
A 2009 metastudy found that patients taking omega-3 supplements with a higher EPA:DHA ratio experienced fewer depressive symptoms. The studies provided evidence that EPA may be more efficacious than DHA in treating depression. However, this metastudy concluded that due to the identified limitations of the included studies, larger, randomized trials are needed to confirm these findings.[40]

On September 8, 2004, the U.S. Food and Drug Administration gave "qualified health claim" status to EPA and DHA omega−3 fatty acids, stating, "supportive but not conclusive research shows that consumption of EPA and DHA [omega−3] fatty acids may reduce the risk of coronary heart disease".[98] This updated and modified their health risk advice letter of 2001 (see below).

The effect of fish oil on incident atrial fibrillation has not been studied in large randomized trials, and observational population-based trials show mixed results. The Danish Diet, Cancer and Health Study, and the Rotterdam Study followed 47,000 and 5100 middle-aged adults, respectively.45,46 Neither study found that the consumption of fish oil affected the incidence of atrial fibrillation. Similar findings were seen in the Women’s Health Initiative where there was no association between fish and omega-3 FA intake regarding incident atrial fibrillation.47 However, in a 12-year prospective, observational study of 4815 adults over the age of 65, daily fish consumption was associated with a 31% risk reduction in incident atrial fibrillation.48


“Lipid peroxidation induced by DHA enrichment modifies paracellular permeability in Caco-2 cells: protective role of taurine.” We conclude that hydrogen peroxide and peroxynitrite may be involved in the DHA-induced increase in paracellular permeability and that the protective role of taurine may be in part related to its capacity to counteract the effects of hydrogen peroxide.
Sala-Vila A, Díaz-López A, Valls-Pedret C, et al.; Prevención con Dieta Mediterránea (PREDIMED) Investigators. Dietary marine ?-3 fatty acids and incident sight-threatening retinopathy in middle-aged and older individuals with type 2 diabetes: Prospective investigation from the PREDIMED trial. JAMA Ophthalmol. 2016;134(10):1142-1149. View abstract.
Meta-analyses (research that combines and analyzes results of multiple studies) generally suggest that the omega-3s are effective, but the findings are not unanimous because of variability between doses, ratios of EPA to DHA, and other study design issues. The most effective preparations appear to have at least 60% EPA relative to DHA. While DHA is thought to be less effective as an antidepressant, it may have protective effects against suicide. Recent work at Massachusetts General Hospital and Emory University suggests that depressed individuals who are overweight and have elevated inflammatory activity may be particularly good candidates for EPA treatment.
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.
Maternal nutrition guidelines have always stressed a diet including sufficient caloric and protein requirements, but recently fatty acids have also been deemed important (17). This is partially due to the fact that EPA and DHA supplementation during pregnancy has been associated with multiple benefits for the infant (Table 1). During pregnancy, the placenta transfers nutrients, including DHA, from the mother to the fetus (18). The amount of omega-3 fatty acid in the fetus is correlated with the amount ingested by the mother, so it is essential that the mother has adequate nutrition (19). The 2010 U.S. Department of Health and Human Services dietary guidelines recommend that women who are pregnant or breastfeeding should “consume 8 to 12 ounces of seafood per week from a variety of seafood types” (12). Ingesting 8–12 oz of seafood per week, depending on the type of fish, is equivalent to ∼300–900 mg EPA+DHA per day. Unfortunately, this amount is not being met by most mothers in the United States and Canada, which means that infants many not be receiving adequate amounts of these vital nutrients in the womb (20).
Five studies with 7 data sets recruited participants without specific clinical conditions.36,47,51,55,60 The main results revealed that there was no significant difference in the association of treatment with reduced anxiety symptoms between patients receiving omega-3 PUFA treatment and those not receiving it (k, 5; Hedges g, –0.008; 95% CI, –0.266 to 0.250; P = .95) (Figure 3A). Fourteen studies with 14 data sets recruited participants with specific clinical diagnoses.33-35,48-50,52-54,56-59,61 The main results revealed a significantly greater association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 14; Hedges g, 0.512; 95% CI, 0.119-0.906; P = .01) (Figure 3A). Furthermore, according to the interaction test, the association of omega-3 PUFA treatment with reduced anxiety symptoms was significantly stronger in subgroups with specific clinical diagnoses than in subgroups without specific clinical conditions (P = .03).

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.
• Fish oil – Fish oil is among the primary ways that people enhance their intake of omega-3 fats. High-quality fish oils can certainly provide many health benefits. However, this oil is weak in antioxidants. This means that as you increase your omega-3 intake through fish oil consumption, you actually increase your need for added antioxidant protection.
When it comes to fat, there's one type you don’t want to cut back on: omega-3 fatty acids. Two crucial ones -- EPA and DHA -- are primarily found in certain fish. ALA (alpha-linolenic acid), another omega-3 fatty acid, is found in plant sources such as nuts and seeds. Not only does your body need these fatty acids to function, but also they deliver some big health benefits.
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.

According to research conducted at Harvard University, omega-3 fatty acid deficiency is officially one of the top 10 causes of death in America, claiming the lives of up to 96,000 people each year. Out of the 12 dietary, lifestyle and metabolic risk factors examined in the study, omega-3 fatty acid deficiency ranked as the sixth highest killer of Americans. (1) These deaths are considered preventable since getting enough omega 3-fatty acids in your diet can ward off this now common cause of death, and fish oil benefits omega-3 intake as a potent omega-3 source.

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]

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.
High triglycerides. Most research shows that fish oil from supplements and food sources can reduce triglyceride levels. The effects of fish oil appear to be the greatest in people who have very high triglyceride levels. Also the amount of fish oil consumed seems to directly affect how much triglyceride levels are reduced. Some fish oil supplements including Lovaza, Omtryg, and Epanova have been approved by the FDA to lower triglycerides.
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