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.

The Cochrane researchers found that increasing long-chain omega 3 provides little if any benefit on most outcomes that they looked at. They found high certainty evidence that long-chain omega 3 fats had little or no meaningful effect on the risk of death from any cause. The risk of death from any cause was 8.8% in people who had increased their intake of omega 3 fats, compared with 9% in people in the control groups.
A certain kidney disease called IgA nephropathy. Some research shows that long-term but not short-term use of fish oil can slow the loss of kidney function in high-risk patients with IgA nephropathy. Fish oil might have greater effects when taken at higher doses. Also, it might be most effective in people with IgA nephropathy who have higher levels of protein in the urine.

Despite this one study, you should still consider eating fish and other seafood as a healthy strategy. If we could absolutely, positively say that the benefits of eating seafood comes entirely from omega-3 fats, then downing fish oil pills would be an alternative to eating fish. But it’s more than likely that you need the entire orchestra of fish fats, vitamins, minerals, and supporting molecules, rather than the lone notes of EPA and DHA.
Abnormal cholesterol or fat levels in the blood (dyslipidemia). There is conflicting evidence about the effects of fish oil on cholesterol and fat levels in the blood. Some research shows that taking fish oil can lower triglyceride levels, low density lipoprotein (LDL or "bad") cholesterol, and increase high density lipoprotein (HDL or "good") cholesterol in people with abnormal cholesterol levels. However, other research shows that taking fish oil daily does not have this effect.
Three randomized trials assessing more than 600 patients with known malignant ventricular arrhythmia were carried out under the protection of implanted cardioverter defibrillator (ICD) therapy.41–43 In all 3 of the trials, 75% of the patients had ischemic heart disease, survived ventricular tachycardia or ventricular fibrillation and were randomized to 1 to 3 g/d of fish oil. In the first trial of its kind, 402 patients with ICDs were randomized to either a fish oil or an olive oil supplement.41 Although statistical significance was not reached, after approximately 1 year the primary end-point of time to first ICD cardioversion for ventricular tachycardia or fibrillation or death from any cause was longer in the fish oil group. This finding was not replicated in a trial of 200 patients who were randomized to either fish oil or a placebo and followed for a median of approximately 2 years.42 In fact, time to first ICD cardioversion was not changed and the incidence of recurrent ventricular tachycardia and fibrillation was more common in the group assigned to fish oil. In the largest trial, 546 patients were randomized to supplemental fish oil or a placebo and were followed for a mean period of 1 year.43 The primary outcome of the rate of ICD cardioversion or all-cause mortality was not reduced. It was concluded in a recent meta-analysis of these trials that fish oil did not have a protective effect.44
Thusgaard, M., Christensen, J. H., Morn, B., Andersen, T. S., Vige, R., Arildsen, H., Schmidt, E. B., and Nielsen, H. Effect of fish oil (n-3 polyunsaturated fatty acids) on plasma lipids, lipoproteins and inflammatory markers in HIV-infected patients treated with antiretroviral therapy: a randomized, double-blind, placebo-controlled study. Scand.J.Infect.Dis. 2009;41(10):760-766. View abstract.
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.
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).

This article had several limitations and the findings need to be considered with caution. First, our participant population is too heterogeneous because of our broad inclusion criteria, which might be true if considering current Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases diagnostic systems. However, the novel Research Domain Criteria consider anxiety to be one of the major domains in Negative Valence Systems. Trials should be conducted in populations in which anxiety is the main symptom irrespective of the presence or absence of diagnosis of anxiety disorder. Second, because of the limited number of recruited studies and their modest sample sizes, the results should not be extrapolated without careful consideration. Third, the significant heterogeneity among the included studies (Cochran Q, 178.820; df, 18; I2, 89.934%; P < .001) with potential influence by some outlier studies, such as the studies by Sohrabi et al56 and Yehuda et al,61 would be another major concern. Therefore, clinicians should pay attention to this aspect when applying the results of the current meta-analysis to clinical practice, particularly when considering the subgroups of these 2 studies (ie, subgroups with specific clinical diagnoses, with <2000 mg/d, with EPA <60%, and with placebo-controlled trials).
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 American Heart Association (AHA) recommends that everyone eats fish (particularly fatty, coldwater fish) at least twice a week. Salmon, mackerel, herring, sardines, lake trout, and tuna are especially high in omega-3 fatty acids. While foods are your best bet for getting omega-3s in your diet, fish oil supplements are also available for those who do not like fish. The heart-healthy benefits of regular doses of fish oil supplements are unclear, so talk to your doctor to see if they're right for you. If you have heart disease or high triglyceride levels, you may need even more omega-3 fatty acids. Ask your doctor if you should take higher doses of fish oil supplements to get the omega-3s you need.

Dyerberg, J., Eskesen, D. C., Andersen, P. W., Astrup, A., Buemann, B., Christensen, J. H., Clausen, P., Rasmussen, B. F., Schmidt, E. B., Tholstrup, T., Toft, E., Toubro, S., and Stender, S. Effects of trans- and n-3 unsaturated fatty acids on cardiovascular risk markers in healthy males. An 8 weeks dietary intervention study. Eur.J.Clin.Nutr. 2004;58(7):1062-1070. View abstract.


Nielsen, G. L., Faarvang, K. L., Thomsen, B. S., Teglbjaerg, K. L., Jensen, L. T., Hansen, T. M., Lervang, H. H., Schmidt, E. B., Dyerberg, J., and Ernst, E. The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial. Eur J Clin Invest 1992;22(10):687-691. View abstract.
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.
The most widely available dietary source of EPA and DHA is oily fish, such as salmon, herring, mackerel, anchovies, menhaden, and sardines. Oils from these fish have a profile of around seven times as much omega−3 as omega−6. Other oily fish, such as tuna, also contain n-3 in somewhat lesser amounts. Consumers of oily fish should be aware of the potential presence of heavy metals and fat-soluble pollutants like PCBs and dioxins, which are known to accumulate up the food chain. After extensive review, researchers from Harvard's School of Public Health in the Journal of the American Medical Association (2006) [110] reported that the benefits of fish intake generally far outweigh the potential risks. Although fish are a dietary source of omega−3 fatty acids, fish do not synthesize them; they obtain them from the algae (microalgae in particular) or plankton in their diets.[111] In the case of farmed fish, omega-3 fatty acids is provided by fish oil; In 2009, 81% of the global fish oil production is used by aquaculture.[112]
Doses for depression range from less than 1 g/day to 10 g/day, but most studies use doses between 1 and 2 g/day. In my practice, I recommend 1 to 2 g/day of an EPA+DHA combination, with at least 60% EPA, for major depression. I am more cautious in patients with bipolar depression, because the omega-3s may bring on mania, as can most antidepressants. In these individuals, I recommend using omega-3 cautiously, and preferably in combination with a prescription mood stabilizer.
The competition between EPA and DHA during digestion and absorption and the fact that DHA appears to ‘block’ the therapeutic actions of EPA can therefore be an issue if we are looking to optimise the benefits associated with EPA (Martins 2009; Bloch & Qawasmi et al, 2011; Sublette et al, 2011). High dose, high concentration and high ratio EPA supplements increase the effectiveness in depression studies, and pure EPA-only is optimal. Depression is also a condition with an inflammatory basis, so this is likely another significant reason for EPA being the key player – its antagonistic relationship with the inflammatory omega-3 AA (arachidonic acid) is very effective at reducing inflammation.

A scientific review in 2014 evaluated study findings on omega-3 intake in relation to the prevention and treatment of breast cancer, the most prevalent cancer among women. The review found that EPA and DHA, as well as ALA, can differentially inhibit breast tumor development. According to this review, there is solid evidence to support the use of omega-3s as “a nutritional intervention in the treatment of breast cancer to enhance conventional therapeutics, or potentially lowering effective doses.” (16) Additionally, a 2016 study found that “very high fish consumption in early adulthood to midlife may be associated with decreased risk of breast cancer.” (17)


The differing actions of EPA and DHA, together with their competitive uptake, help to explain why studies that attempt to use standard fish oil therapeutically (where DHA and EPA are combined, in a natural ratio of approximately 1.5:1) are either less beneficial than expected, or even completely ineffective. Standard EPA/DHA fish oils are more suitable for everyday wellbeing, to compensate for a lack of fish in the diet and to meet a suggested intake.
Age-related macular degeneration (AMD) is an eye disease that can cause vision loss in older people. Two major National Institutes of Health (NIH)-sponsored studies, called Age-Related Eye Disease Study (AREDS) and Age-Related Eye Disease Study 2 (AREDS2), showed that dietary supplements containing specific combinations of vitamins, antioxidants, and zinc helped slow the progression of AMD in people who were at high risk of developing the advanced stage of this disease. AREDS2, which had more than 4,000 participants and was completed in 2013, also tested EPA and DHA. The results showed that adding these omega-3s to the supplement formulation didn’t provide any additional benefits. Other, smaller studies of omega-3 supplements also haven’t shown them to have a beneficial effect on the progression of AMD. 

The differing actions of EPA and DHA, together with their competitive uptake, help to explain why studies that attempt to use standard fish oil therapeutically (where DHA and EPA are combined, in a natural ratio of approximately 1.5:1) are either less beneficial than expected, or even completely ineffective. Standard EPA/DHA fish oils are more suitable for everyday wellbeing, to compensate for a lack of fish in the diet and to meet a suggested intake.
Muñoz MA, Liu W, Delaney JA, Brown E, Mugavero MJ, Mathews WC, Napravnik S, Willig JH, Eron JJ, Hunt PW, Kahn JO, Saag MS, Kitahata MM, Crane HM. Comparative effectiveness of fish oil versus fenofibrate, gemfibrozil, and atorvastatin on lowering triglyceride levels among HIV-infected patients in routine clinical care. J Acquir Immune Defic Syndr 2013;64(3):254-60. View abstract.

A lot of the benefit of fish oil seems to come from the omega-3 fatty acids that it contains. Interestingly, the body does not produce its own omega-3 fatty acids. Nor can the body make omega-3 fatty acids from omega-6 fatty acids, which are common in the Western diet. A lot of research has been done on EPA and DHA, two types of omega-3 acids that are often included in fish oil supplements.

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