2. Omega-3 normalizes and regulates your cholesterol triglyceride levels. Compared to a statin, both fish oil and krill oil are more efficient in doing this. According to a study comparing the efficiency of krill and fish oils in reducing triglyceride levels,7 both oils notably reduced the enzyme activity that causes the liver to metabolize fat, but krill had a more pronounced effects, reducing liver triglycerides significantly more.
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
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.
Luo, J Rizkalla SW Vidal H Oppert JM Colas C Boussairi A Guerre-Millo M Chapuis AS Chevalier A Durand G Slama G. Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study. Diabetes Care. 1998;21(5):717-724. View abstract.
Fish oil supplements are available as liquids or capsules. Some capsules are enteric-coated to pass through the stomach before dissolving in the small intestine, thus helping prevent indigestion and "fish burps". Poorly manufactured enteric-coated products have the potential to release ingredients too early. ConsumerLab.com, a for-profit supplement testing company, reported that 1 of the 24 enteric-coated fish oil supplements it evaluated released ingredients prematurely.[48]
Fish or seafood allergy: Some people who are allergic to seafood such as fish might also be allergic to fish oil supplements. There is no reliable information showing how likely people with seafood allergy are to have an allergic reaction to fish oil. Until more is known, advise patients allergic to seafood to avoid or use fish oil supplements cautiously.
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.

Interestingly, the results are also consistent with our recent findings that somatic anxiety is associated with omega-3 PUFA deficits and the genetic risks of PUFA metabolic enzyme cytosolic phospholipase A2 in major depressive disorder62,63 and interferon α–induced neuropsychiatric syndrome.63,64 Brain membranes contain a high proportion of omega-3 PUFAs and their derivatives and most animal and human studies suggest that a lack of omega-3 PUFAs in the brain might induce various behavioral and neuropsychiatric disorders,16,65-70 including anxiety-related behaviors.12,18,19,32,49,71 Emerging evidence suggests that omega-3 PUFAs interfere with and possibly control several neurobiological processes, such as neurotransmitter systems, neuroplasticity, and inflammation,12,72 which is postulated to be the mechanism underlying anxiety and depression.
There was a significantly greater association of treatment with reduced anxiety symptoms in participants receiving omega-3 PUFAs than in those not receiving omega-3 PUFAs in the subgroup with an EPA percentage less than 60% (k, 11; Hedges g, 0.485; 95% CI, 0.017-0.954; P = .04; Figure 4)35,49,52,54-61 but 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 subgroup with an EPA percentage of at least 60% (k, 9; Hedges g, 0.092; 95% CI, –0.102 to 0.285; P = .35) (Figure 4).33,34,36,47,48,50,51,53,60 There were no significantly different estimated effect sizes between these 2 subgroups by the interaction test (P = .13).
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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]
Throughout their history, the Council for Responsible Nutrition and the World Health Organization have published acceptability standards regarding contaminants in fish oil. The most stringent current standard is the International Fish Oils Standard.[108][non-primary source needed] Fish oils that are molecularly distilled under vacuum typically make this highest-grade; levels of contaminants are stated in parts per billion per trillion.[citation needed][109]
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.
Recently another Omega-3 fatty acid, DPA (Docosapentaenoic Acid) has been discussed more frequently in the scientific community, as a new and very potent Omega-3 fatty acid. Previously thought to work in through EPA and DHA we are now learning it has very distinct functions in the body. All three of these polyunsaturated fats play an important role in the functioning of our bodies.
Why would someone foul a perfectly good box of rotini with omega 3 oils? This is based on the belief that omega 3 fatty acids reduce heart disease and vascular risk, probably through reducing blood pressure and cholesterol. This is a plausible claim, but as we see over and over again in medicine, plausibility (while nice) is insufficient as a basis for clinical claims.
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.
Respected health care organizations proposed intake recommendations for oily fish of two servings per week for healthy adults, which equates to approximately a daily total of 500 milligrams (mg) EPA and DHA.‡ The recommendation encourages adults already with or at-risk of developing cardiovascular disease to talk to their primary healthcare professional about supplementing with amounts greater than 500 mg of EPA and DHA per day. Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease.
DHA is especially vital for infant and child brain and nervous system development, as well as visual function. In older children, high DHA levels have been shown to improve learning ability, while deficiencies have been linked to learning problems and ADHD. And in adults, some studies have shown that DHA helps protect against cognitive decline and Alzheimer’s disease.

Several large trials have evaluated the effect of fish or fish oils on heart disease. In the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardio (known as the GISSI Prevention Trial), heart attack survivors who took a 1-gram capsule of omega-3 fats every day for three years were less likely to have a repeat heart attack, stroke, or die of sudden death than those who took a placebo. (2) Notably, the risk of sudden cardiac death was reduced by about 50 percent. In the more recent Japan EPA Lipid Intervention Study (JELIS), participants who took EPA plus a cholesterol-lowering statin were less likely to have a major coronary event (sudden cardiac death, fatal or nonfatal heart attack, unstable angina, or a procedure to open or bypass a narrowed or blocked coronary artery) than those who took a statin alone. (3)

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.
Maximizing the benefits you get from omega-3s is highly dependent on how they are absorbed and transported throughout your body. Although these fatty acids are water soluble, they cannot be easily transported into your blood in their free form. Therefore, they need to be packaged in lipoprotein vehicles for them to be better absorbed into your bloodstream.
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/

Among the 16 studies comparing the effect of omega-3 PUFA treatment with that of the placebo,33,34,36,47-49,51-53,55-61 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, 16; Hedges g, 0.372; 95% CI, 0.032-0.712; P = .03; eFigure 3 in the Supplement). The meta-analysis of the subgroup focusing on non–placebo-controlled trials also showed a significantly greater association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 3; Hedges g, 0.399; 95% CI, 0.154-0.643; P = .001).35,50,54

Fish oil has been shown to have a direct electrophysiological effect on the myocardium. Initial experience with animal ischemia models demonstrated that the ventricular fibrillation threshold was increased in both animals fed or infused with omega-3 FA.23,24 This progressed to a demonstration, on a cellular and ion channel level, that omega-3 FA reduce both sodium currents and L-type calcium currents.25–29 It is hypothesized that during ischemia, a reduction in the sodium ion current protects hyperexcitable tissue, and a reduction in the calcium ion current reduces arrhythmogenic depolarizing currents.30
Most people get far too little omega-3s in their diet. In fact, research consistently indicates that the majority of Americans have just slightly more than half the amount of EPA and DHA in their tissues than they need for optimum brain and body health. This is partly due to a high dietary intake of unhealthy fats combined with an inadequate intake of EPA and DHA.
Of great clinical importance, EPA and DHA supplementation during pregnancy has been associated with longer gestation and increased concentrations of EPA and DHA in fetal tissues (21). In 2005, preterm births accounted for 12.7% of all births in the United States, increasing the likelihood of health complications (22). Carrying a baby to term is very important because prematurity is the cause of various infant diseases and can lead to death; preterm delivery is an underlying factor for 85% of the deaths of normally formed infants (23). One mechanism by which EPA and DHA may decrease the incidence of preterm birth is by decreasing prostaglandin E2 and prostaglandin F2α production, therefore reducing inflammation within the uterus, which could be associated with preterm labor (21, 24). Several studies investigated EPA and DHA intake during pregnancy and its correlation with longer gestation. Conclusions were that EPA+DHA supplementation during pregnancy delayed the onset of delivery to term or closer to term; however, supplementation did not delay delivery to the point of being post-term (20, 23, 25). This supports the evidence that EPA+DHA ingestion leads to optimal pregnancy length. EPA+DHA supplementation reduced the HR of preterm delivery by 44% (95% CI: 14–64%) in those who consumed relatively low amounts of fish and 39% (95% CI: 16–56%) in those who consumed medium amounts of fish; however, a level of statistical significance was not met (P = 0.10) (23). The Judge et al. (20) study found that women who had DHA supplementation from gestation week 24 until full-term delivery carried their infants significantly (P = 0.019) longer than did the women in the placebo group. One study found that DHA supplementation after gestation week 21 led to fewer preterm births (<34 wk of gestation) in the DHA group compared with the control group (1.09% vs. 2.25%; adjusted RR, 0.49; 95% CI: 0.25–0.94; P = 0.03). Also, mean birth weight was 68 g heavier (95% CI: 23–114 g; P = 0.003) and fewer infants were of low birth weight in the DHA group compared with the control group (3.41% vs. 5.27%; adjusted RR, 0.65; 95% CI: 0.44–0.96; P = 0.03) (25).
When taking fish oil, more is not always better. Remember that you want it to stay in a balanced ratio with omega-6 fats. For most people, I recommend a 1,000-milligram dose of fish oil daily as a good amount and the most scientifically studied dosage. I highly recommend not taking more than that unless directed to under the supervision of a doctor.

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.

Thanks for the informative article. You mentioned that those taking high doses of DHA should supplement it with trace amounts of GLA. What GLA source would you recommend, and how much per day? I will be taking around 3400 mg of epa and 2200 mg DHA per day. I've heard that Borage Oil is more potent in GLA than evening primrose, but that it can lead to increased clotting and increased risk of heart attack, stroke, etc due to increased thromboxane B2. The main reason I want to stay away from the primrose is because it is extremely rich in linoleic acid. Thanks.
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.
To date, no studies have assessed mortality or nonfatal MI in diabetic patients treated with fish oil.52–54 A recent comprehensive meta-analysis analyzed the effect of fish oil supplements on metabolic parameters when added to usual care in patients with type 2 diabetes mellitus or impaired glucose tolerance.54 The meta-analysis included a total of 23 small, randomized trials with over 1000 patients that were assessed for lipid and insulin resistance parameters. At a mean follow-up of approximately 9 weeks, triglyceride reduction was accomplished but no significant changes were seen in total cholesterol, high-density lipoprotein-cholesterol, HgA1c levels, fasting glucose levels, fasting insulin, or in body weight. The largest randomized trial to date assessed approximately 400 patients with impaired glucose tolerance or insulin-dependent diabetes mel-litus, and as reflected in the larger meta-analysis, found no effect of moderate to high doses of fish oil on diabetic parameters.55 There are insufficient randomized data to comment on the combination of fish oil and specific diabetes medications and related mortality and/or morbidity.
There is some evidence that omega−3 fatty acids are related to mental health,[47] including that they may tentatively be useful as an add-on for the treatment of depression associated with bipolar disorder.[48] Significant benefits due to EPA supplementation were only seen, however, when treating depressive symptoms and not manic symptoms suggesting a link between omega−3 and depressive mood.[48] There is also preliminary evidence that EPA supplementation is helpful in cases of depression.[49] The link between omega−3 and depression has been attributed to the fact that many of the products of the omega−3 synthesis pathway play key roles in regulating inflammation (such as prostaglandin E3) which have been linked to depression.[50] This link to inflammation regulation has been supported in both in vitro[51] and in vivo studies as well as in meta-analysis studies.[33] The exact mechanism in which omega−3 acts upon the inflammatory system is still controversial as it was commonly believed to have anti-inflammatory effects.[52]
Researchers are taking a hard look at a different sort of balance, this one between possible effects of marine and plant omega-3 fats on prostate cancer. Results from the Health Professionals Follow-up Study and others show that men whose diets are rich in EPA and DHA (mainly from fish and seafood) are less likely to develop advanced prostate cancer than those with low intake of EPA and DHA. (6) At the same time, some-but not all-studies show an increase in prostate cancer and advanced prostate cancer among men with high intakes of ALA (mainly from supplements). However, this effect is inconsistent. In the very large Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, for example, there was no link between ALA intake and early, late, or advanced prostate cancer. (7)
Fish oil is useful in the treatment of arthritis, rheumatism, Raynaud’s symptoms and similar conditions. Using the fish oil can help in reducing the need for large dosages of NSAIDs (non-steroidal anti-inflammatory drugs). The Royal Adelaide Hospital and the University of Newcastle, located in Australia, have reported that fish oil has shown positive effects in the treatment of arthritis. In cases of osteoarthritis, fish oil can be helpful in reducing the impact of enzymes that destroy cartilage.
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]

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.
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).
Damage to the kidneys caused the drug cyclosporine. Cyclosporine is a medication that reduces the chance of organ rejection after an organ transplant. Taking fish oil seems to prevent kidney damage in people taking this drug. Fish oil also seems to improve kidney function during the recovery phase following the rejection of a transplanted organ in people taking cyclosporine.
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