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.
Back in 2013, a study came out that made a lot of people concerned about fish oil supplements and cancer. The study, published in the Journal of the National Cancer Institute, showed that men who consume the largest amount of fish oil had a 71 percent higher risk of high-grade prostate cancer and a 43 percent increase in all types of prostate cancer. The study was conducted on 2,227 men, of which 38 percent of the men already had prostate cancer. (39)
Omega 3 fatty acids are monounsaturated fats that come from food sources—primarily cold water fish (eg, salmon, trout, tuna, mackerel, and herring)—that contain EPA (eicosapentaenoic acid) and docosahexaenoic acid (DHA). Other fatty acids are derived from plant-derived sources of food—including nuts (especially walnuts) and seeds (eg, flax, chia, sunflower)—that have primarily ALA (alpha-linolenic acid).
If you find yourself in a position where you are just not eating any of these foods, and you want to get enough omega-3 fatty acids, then I think fish oil is okay, but I would limit not the amount of fish oil but the amount listed on the label of EPA and DHA combined. I would limit that amount to around 250 milligrams per day because I don’t think most people need more than that. Some signs that you might not be getting enough omega-3 fatty acids include chronic low-grade inflammation, poor visual acuity, slower mental processing, trouble learning, and possibly Alzheimer’s disease and psychiatric conditions, like depression, anxiety, and attention deficit and hyperactivity disorder, ADHD.

The chemical structures of EPA and DHA are very similar and they compete for uptake and processing resources. During digestion, the triglyceride molecules in standard fish oil are broken down into a mono glycerol and two free fatty acids, small enough to be absorbed into cells of the gut lining. More often than not, DHA is the fatty acid that remains attached to the glycerol backbone, meaning in essence that DHA gets a ‘free pass’ into the gut, while the remaining free fatty acids (more often EPA) must reattach onto a glycerol molecule or risk being oxidised and used as fuel. The implication of this is that DHA levels in our cells are often concentrated at the expense of EPA after absorption when taking EPA and DHA in the standard ratio of 1.5 to 1.


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)
Arsenault, L. N., Matthan, N., Scott, T. M., Dallal, G., Lichtenstein, A. H., Folstein, M. F., Rosenberg, I., and Tucker, K. L. Validity of estimated dietary eicosapentaenoic acid and docosahexaenoic acid intakes determined by interviewer-administered food frequency questionnaire among older adults with mild-to-moderate cognitive impairment or dementia. Am J Epidemiol 7-1-2009;170(1):95-103. View abstract.
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Several large studies have linked higher blood levels of long-chain omega-3s with higher risks of prostate cancer. However, other research has shown that men who frequently eat seafood have lower prostate cancer death rates and that dietary intakes of long-chain omega-3s aren’t associated with prostate cancer risk. The reason for these apparently conflicting findings is unclear. 
EPA, which is eicosapentaenoic acid, and DHA, which is docosahexaenoic acid, are two types of omega-3 fatty acids that are most commonly found in seafood. These polyunsaturated fats are known to have preventative health benefits and have been studied for their role in treating certain chronic conditions. In addition to dietary sources, certain supplements such as fish oil, are also rich in EPA and DHA.
Brain function and vision rely on dietary intake of DHA to support a broad range of cell membrane properties, particularly in grey matter, which is rich in membranes.[61][62] A major structural component of the mammalian brain, DHA is the most abundant omega−3 fatty acid in the brain.[63] It is under study as a candidate essential nutrient with roles in neurodevelopment, cognition, and neurodegenerative disorders.[61]
42. Cawood AL, Ding R, Napper FL, Young RH, Williams JA, Ward MJ, Gudmundsen O, Vige R, Payne SP, Ye S, et al. Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. Atherosclerosis. 2010;212:252–9. [PubMed]
Marchioli, R., Barzi, F., Bomba, E., Chieffo, C., Di, Gregorio D., Di, Mascio R., Franzosi, M. G., Geraci, E., Levantesi, G., Maggioni, A. P., Mantini, L., Marfisi, R. M., Mastrogiuseppe, G., Mininni, N., Nicolosi, G. L., Santini, M., Schweiger, C., Tavazzi, L., Tognoni, G., Tucci, C., and Valagussa, F. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 4-23-2002;105(16):1897-1903. View abstract.
To evaluate the potential placebo effect, we made further subgrouping analyses. In the subgroups of studies using placebo controls, the omega-3 PUFAs still revealed a consistent positive anxiolytic association with anxiety symptoms. These phenomena meant that the anxiolytic effect of omega-3 PUFAs is probably not entirely owing to the placebo effect.

Omega-3s have been studied for other conditions, with either inconclusive or negative results. These conditions include allergies, atopic eczema (an allergic skin condition), cystic fibrosis, diabetes, inflammatory bowel diseases (Crohn’s disease or ulcerative colitis), intermittent claudication (a circulatory problem), nonalcoholic fatty liver disease, and osteoporosis. 

Second, quality matters. It is important to purchase fish oil from a reputable manufacturer that follows Good Manufacturing Practices (GMPs) and takes the necessary steps to purify the oil. In choosing a brand like Nature Made®, the #1 Pharmacist Recommended Omega-3/Fish Oil Brand*, you can rest assured knowing Nature Made has a strong commitment to making quality supplements so you can experience the benefits of fish oil.
According to the National Psoriasis Foundation, fish oil can aid in preventing or slowing heart disease, which is especially great for psoriasis and psoriatic arthritis sufferers who are at a higher risk of developing heart disease. (27) When it comes to using fish oil supplements for the alleviation of psoriasis symptoms, studies have been mixed with some showing improvement but others showing no effect. If you suffer from psoriasis, you may want to try a fish oil supplement, or else I highly recommend that you make sure to have fish rich in omega-3s regularly.

Omega-3 fatty acids, which are found abundantly in fish oil, are increasingly being used in the management of cardiovascular disease. It is clear that fish oil, in clinically used doses (typically 4 g/d of eicosapentaenoic acid and docosahexaenoic acid) reduce high triglycerides. However, the role of omega-3 fatty acids in reducing mortality, sudden death, arrhythmias, myocardial infarction, and heart failure has not yet been established. This review will focus on the current clinical uses of fish oil and provide an update on their effects on triglycerides, coronary artery disease, heart failure, and arrhythmia. We will explore the dietary sources of fish oil as compared with drug therapy, and discuss the use of fish oil products in combination with other commonly used lipid-lowering agents. We will examine the underlying mechanism of fish oil’s action on triglyceride reduction, plaque stability, and effect in diabetes, and review the newly discovered anti-inflammatory effects of fish oil. Finally, we will examine the limitations of current data and suggest recommendations for fish oil use.
Fish oil supplements came under scrutiny in 2006, when the Food Standards Agency in the UK and the Food Safety Authority of Ireland reported PCB levels that exceeded the European maximum limits in several fish oil brands,[60][61] which required temporary withdrawal of these brands. To address the concern over contaminated fish oil supplements, the International Fish Oil Standards (IFOS) Program, a third-party testing and accreditation program for fish oil products, was created by Nutrasource Diagnostics Inc. in Guelph, Ontario, Canada.[62]

Another small study had all volunteers consume the same exact control diet and substituted fish oil for visible fats (things like butter and cream). The volunteers consumed six grams of fish oil each day for three weeks. They found that body fat mass decreased with the intake of fish oil. The researchers conclude that dietary fish oil reduces body fat and stimulates the use of fatty acids for the production of energy in healthy adults. (33a)
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.
Results  In total, 1203 participants with omega-3 PUFA treatment (mean age, 43.7 years; mean female proportion, 55.0%; mean omega-3 PUFA dosage, 1605.7 mg/d) and 1037 participants without omega-3 PUFA treatment (mean age, 40.6 years; mean female proportion, 55.0%) showed an association between clinical anxiety symptoms among participants with omega-3 PUFA treatment compared with control arms (Hedges g, 0.374; 95% CI, 0.081-0.666; P = .01). Subgroup analysis showed that the association of treatment with reduced anxiety symptoms was significantly greater in subgroups with specific clinical diagnoses than in subgroups without clinical conditions. The anxiolytic effect of omega-3 PUFAs was significantly better than that of controls only in subgroups with a higher dosage (at least 2000 mg/d) and not in subgroups with a lower dosage (<2000 mg/d).

In addition, there was no significant difference in the association of treatment with reduced anxiety symptoms between participants receiving omega-3 PUFAs and those not receiving omega-3 PUFAs in the adolescent subgroup (aged <18 years) (k, 3; Hedges g, 0.020; 95% CI, –0.209 to 0.250; P = .86),48,53,57 in the adult subgroup (aged ≥18 years but <60 years) (k, 11; Hedges g, 0.388; 95% CI, –0.012 to 0.788; P = .06),33,35,36,47,49-51,54-56,59 or in the elderly subgroup (aged ≥60 years) (k, 3; Hedges g, –0.112; 95% CI, –0.406 to 0.181; P = .45).52,58,60 These insignificant results might be due to the smaller sample sizes in each subgroup.
Today the only Food and Drug Administration (FDA)-approved form of dietary omega-3 FA supplement is Lovaza (omega-3-acid ethyl esters; GlaxoSmithKline), which contains 375 mg of DHA and 465 mg of EPA per 1 g capsule. The myriad of dietary supplements of fish oil, including Kosher capsules, vary from comparable content to insignificant amounts, and for the most part can include other fats and cholesterols. In comparison, to achieve approximately 1 g of EPA and DHA in a meal, 12 ounces of canned light tuna, 2 to 3 ounces of sardines, 1.5 to 2.5 ounces of farmed Atlantic salmon, or 20 ounces of farmed catfish must be consumed (Table 1).65 Unfortunately, potentially high levels of harmful pollutants offset this source of omega-3 FA. The FDA action level for unacceptably high mercury content in fish is 1.0 μg/g. The mercury level in most fish is at or below 0.1 μg/g, but tilefish, swordfish, and king mackerel have high levels of mercury. The majority of fish species also contain <100 ng/g of polychlorinated biphenyls, which is below the FDA action level of 2000 ng/g. Dioxins, which do not have FDA action levels, are present in the majority of marine life.66
If you find yourself in a position where you are just not eating any of these foods, and you want to get enough omega-3 fatty acids, then I think fish oil is okay, but I would limit not the amount of fish oil but the amount listed on the label of EPA and DHA combined. I would limit that amount to around 250 milligrams per day because I don’t think most people need more than that. Some signs that you might not be getting enough omega-3 fatty acids include chronic low-grade inflammation, poor visual acuity, slower mental processing, trouble learning, and possibly Alzheimer’s disease and psychiatric conditions, like depression, anxiety, and attention deficit and hyperactivity disorder, ADHD.
The number of presenters and the amount of information stuffed into an action-packed few days at times felt overwhelming, even for two dedicated omega-3 enthusiasts like us. But one important message did hit home: The omega-3 index could be a helpful indicator of various health risks, and we should all be paying closer attention to this measurement.
Mercury and polychlorinated biphenyls (PCBs) are common toxins in seafood. Although the U.S. banned the use of PCBs and DDT in 1976, these and other chemicals are still used in half the world's commercial chemical processes. Substances like these can hang around in the air, soil, and water for many years. They end up in the bodies of fish and animals.

Rondanelli, M., Giacosa, A., Opizzi, A., Pelucchi, C., La, Vecchia C., Montorfano, G., Negroni, M., Berra, B., Politi, P., and Rizzo, A. M. Effect of omega-3 fatty acids supplementation on depressive symptoms and on health-related quality of life in the treatment of elderly women with depression: a double-blind, placebo-controlled, randomized clinical trial. J.Am.Coll.Nutr. 2010;29(1):55-64. View abstract.


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.
Fearon, K. C., Von Meyenfeldt, M. F., Moses, A. G., Van Geenen, R., Roy, A., Gouma, D. J., Giacosa, A., Van Gossum, A., Bauer, J., Barber, M. D., Aaronson, N. K., Voss, A. C., and Tisdale, M. J. Effect of a protein and energy dense n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut 2003;52(10):1479-1486. View abstract.
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.
DHA is vital for early brain development and maintenance, while EPA seems to be closely related to behavior and mood. Together, both molecules provide critical neuroprotective benefits.11 These neuroprotective effects are important for the prevention of age-related brain shrinkage (cortical atrophy). Aging adults with brain shrinkage often experience memory loss, cognitive decline, and an increase in depression.12-14
Makrides et al. (25) Double-blind, placebo-controlled, randomized 2399 (n = 1197 supplemented, n = 1202 placebo; 726 children were followed up with) DHA (fish-oil capsules providing 800 mg/d DHA) Supplementation did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in offspring during early childhood
Secondly, when we consume EPA, it inhibits the production of AA from DGLA and also competes with AA for uptake into cell membranes and can therefore lower the amount of AA in membranes by literally saturating the cell – in essence, it takes up more of the available ‘space’ and displaces AA. When there is less AA present, there is a reduced capacity for it to produce inflammatory products.
Krill oil is a source of omega−3 fatty acids.[116] The effect of krill oil, at a lower dose of EPA + DHA (62.8%), was demonstrated to be similar to that of fish oil on blood lipid levels and markers of inflammation in healthy humans.[117] While not an endangered species, krill are a mainstay of the diets of many ocean-based species including whales, causing environmental and scientific concerns about their sustainability.[118][119][120]
Heart disease. Research suggests that 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.
Augood, C., Chakravarthy, U., Young, I., Vioque, J., de Jong, P. T., Bentham, G., Rahu, M., Seland, J., Soubrane, G., Tomazzoli, L., Topouzis, F., Vingerling, J. R., and Fletcher, A. E. Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes, and associations with neovascular age-related macular degeneration. Am J Clin Nutr 2008;88(2):398-406. View abstract.

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 also POSSIBLY SAFE when given in the vein by a health care professional to infants who cannot take food by mouth. 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.
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