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Metagenics offers a wide range of educational opportunities including webinars, group meetings, and seminars as part of our commitment to continuing functional medicine education. Our goal is to give our practitioners further insight to help address their patients’ unique health needs for a higher level of personalized, lifetime wellness care. We have been sharing this ever-growing body of nutritional and lifestyle research for over 25 years.
Many studies documenting the benefits of omega-3s have been conducted with supplemental daily dosages between 2 and 5 grams of EPA and DHA, more than you could get in 2 servings of fish a week. But that doesn't mean eating fish is an exercise in futility. Many studies document its benefits. For example, a 2003 National Eye Institute study showed that 60- to 80-year-olds eating fish more than twice a week were half as likely to develop macular degeneration as those who ate no fish at all.

Joensen, A. M., Schmidt, E. B., Dethlefsen, C., Johnsen, S. P., Tjonneland, A., Rasmussen, L. H., and Overvad, K. Dietary intake of total marine n-3 polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid and docosapentaenoic acid and the risk of acute coronary syndrome - a cohort study. Br J Nutr 2010;103(4):602-607. View abstract.


Peroxides can be produced when fish oil spoils. A study commissioned by the government of Norway concluded there would be some health concern related to the regular consumption of oxidized (rancid) fish/marine oils, particularly in regards to the gastrointestinal tract, but there is not enough data to determine the risk. The amount of spoilage and contamination in a supplement depends on the raw materials and processes of extraction, refining, concentration, encapsulation, storage and transportation.[51] ConsumerLab.com reports in its review that it found spoilage in test reports it ordered on some fish oil supplement products.[52]

Birch, E. E., Carlson, S. E., Hoffman, D. R., Fitzgerald-Gustafson, K. M., Fu, V. L., Drover, J. R., Castaneda, Y. S., Minns, L., Wheaton, D. K., Mundy, D., Marunycz, J., and Diersen-Schade, D. A. The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Am J Clin Nutr 2010;91(4):848-859. View abstract.

Heart rate variability, a possible surrogate outcome for the risk of sudden death, was assessed in a randomized trial of myocardial infarction (MI) survivors with an ejection fraction of 40%. In the 49 patients that were randomized to either fish oil or olive oil, Holter monitor recordings showed an increase in heart rate variability in the fish oil group.31 In a larger cohort assessed in the Japan EPA Lipid Intervention Study (JELIS),32 however, no difference in heart rate variability could be attributed to fish oil.
Omega-3 fatty acids have been shown to increase platelet responsiveness to subtherapeutic anticoagulation therapies, including aspirin. Recently, it was noted that patient response to aspirin for anticoagulation therapy is widely variable (45), and, thus, the number of patients with a low response to aspirin or aspirin resistance is estimated to range from <1% to 45%, depending on many variables. However, in patients with stable coronary artery disease taking low-dose aspirin, EPA+DHA supplementation has been proven to be as effective as aspirin dose escalation to 325 mg/d for anticoagulation benefits (45). The antiplatelet drug clopidogrel has also been associated with hyporesponsiveness in some patients. This could be attributed to poor patient compliance, differences in genes and platelet reactivity, variability of drug metabolism, and drug interactions. More importantly, in 1 study, patients receiving standard dual antiplatelet therapy (aspirin 75 mg/d and clopidogrel 600-mg loading dose followed by 75 mg/d) were assigned to either EPA+DHA supplementation or placebo. After 1 mo of treatment, the P2Y12 receptor reactivity index (an indicator of clopidogrel resistance) was significantly lower, by 22%, for patients taking EPA+DHA compared with patients taking placebo (P = 0.020) (46).
Under these conditions, it may make sense to try fish oil even at higher doses than what I recommended. There is some evidence that krill oil will get the omega-3 fatty acids better into the brain in the psychiatric conditions that I listed. And there is some evidence that EPA-rich fish oils are better than DHA-rich fish oils for some of those psychiatric conditions as well. So there’s room to play around with the different possibilities if those things apply to you. But for the average case, limit the fish oil to 250 milligrams of EPA and DHA combined when you take it, but in all cases, go for food first, and go for fish oil only after you have exhausted those possibilities.
(How much omega-3 is necessary to increase one’s omega-3 index?  Studies show it can take between 1800 – 2000 mg of EPA/DHA daily to move a person’s index by 4 – 5 percentage points (12). Importantly, this is a much larger dose than you’d get swallowing one or two regular fish oil capsules and could well explain why many traditional omega-3 products fail to deliver results.)

6. Krauss-Etschmann S, Shadid R, Campoy C, Hoster E, Demmelmair H, Jimenez M, Gil A, Rivero M, Veszpremi B, Decsi T, et al. Effects of fish-oil and folate supplementation of pregnant women on maternal and fetal plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid: a European randomized multicenter trial. Am J Clin Nutr. 2007;85:1392–400. [PubMed]
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
Most U.S. adults fail to consume adequate amounts of foods rich in EPA and DHA on a regular basis (at least 8 ounces of fatty fish per week is recommended), and probably consume too many omega-6 fats in comparison (soybean oil, canola oil, cottonseed oil, etc.). This omega-3:omega-6 imbalance can have a negative effect on inflammation patterns and may also be implicated as a contributing factor to other processes related to cellular metabolism, hormone signaling, and even weight regulation.

Your best way to achieve a good balance of omega-3 and omega-6 is by getting your fish oil from wild-caught fish like salmon. However, I still think it is beneficial for some to supplement with a high-quality omega-3 fish oil or cod liver oil. Plus, cold water fish are frequently contaminated with mercury and pesticide residues, making it very difficult to safely achieve recommended levels.
46. Gajos G, Rostoff P, Undas A, Piwowarska W. Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after pci to modify responsiveness to dual antiplatelet therapy) study. J Am Coll Cardiol. 2010;55:1671–8. [PubMed]
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.
“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.
Recent studies have shown that the consumption of fish oil (or, more specifically, the omega-3 fatty acids found in fish oil) can improve fertility in both men and women. DHA, which is a byproduct of omega-3 fatty acids, plays a key role in the mobility of sperm and health of sperm in men. Low blood levels of DHA have been linked to decreased fertility. Animal studies have found that the DHA in fish is vital to changing dysfunctional round-headed sperm into strong swimmers with cone-shaped heads packed with egg-opening proteins. (29)
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.
A Cochrane meta-analysis published in June 2012 found no significant protective effect for cognitive decline for those aged 60 and over and who started taking fatty acids after this age. A co-author of the study said to Time, "Our analysis suggests that there is currently no evidence that omega-3 fatty acid supplements provide a benefit for memory or concentration in later life".[43]
What makes omega-3 fats special? They are an integral part of cell membranes throughout the body and affect the function of the cell receptors in these membranes. They provide the starting point for making hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. They also bind to receptors in cells that regulate genetic function. Likely due to these effects, omega-3 fats have been shown to help prevent heart disease and stroke, may help control lupus, eczema, and rheumatoid arthritis, and may play protective roles in cancer and other conditions.
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.
Omega-3 FA most likely reduce serum triglyceride levels by modulating very-low-density lipoprotein (VLDL) and chylomicron metabolism. There is a consistent finding in the literature that the end effect of fish oil is decreased hepatic secretion of VLDL17—the major endogenous source of triglycerides. This effect occurs most likely through multiple mechanisms, including: (1) decreased synthesis of triglycerides because these omega-3 FA may not be the preferred substrates of the enzyme diacylglycerol O-acyltransferase,18 or they may interact with nuclear transcription factors that control lipogenesis19; cellular metabolism consequently shifts toward a decrease in triglyceride synthesis and an increase in FA oxidation; and (2) the promotion of apolipoprotein B degradation in the liver through the stimulation of an autophagic process.20 This means that fewer VLDL particles can be assembled and secreted. Fish oil may also accelerate VLDL and chylomicron clearance21 by inducing lipoprotein lipase activity.22
In fact, dietary fat intake has been among the most widely studied dietary risk factors for breast and prostate cancers. Two studies from 2002 explain how omega-3 can protect against breast cancer. BRCA1 (breast cancer gene 1) and BRCA2 (breast cancer gene 2) are two tumor suppressor genes that, when functioning normally, help repair DNA damage, a process that also prevents tumor development.

A new Cochrane systematic review, published today in the Cochrane Library, combines the results of seventy-nine randomised trials involving 112,059 people. These studies assessed effects of consuming additional omega 3 fat, compared to usual or lower omega 3, on diseases of the heart and circulation. Twenty-five studies were assessed as highly trustworthy because they were well designed and conducted.
To avoid fish oil supplements containing mercury or other harmful contaminants, purchase supplements from a reputable source that clearly tests for these health-hazardous contaminants in its products. These tests should be ideally conducted by a third-party, and a certificate of analysis should indicate the levels of purity from environmental toxins.
Your best way to achieve a good balance of omega-3 and omega-6 is by getting your fish oil from wild-caught fish like salmon. However, I still think it is beneficial for some to supplement with a high-quality omega-3 fish oil or cod liver oil. Plus, cold water fish are frequently contaminated with mercury and pesticide residues, making it very difficult to safely achieve recommended levels.

Our Clinical Services Team - staffed by clinicians and other nutritional experts - answer technical questions about our nutritional formulas and the most effective ways to recommend them in a variety of protocols. And our product representatives help practitioners grow their business in many more ways than suggesting practice-appropriate nutritional products.
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.
Unsafe for children. Fish oil supplements are not considered safe for children. Too much of this fat in their system can lead to a chemical imbalance in the brain which could stunt healthy growth and development. Because of this, and the possible exposure to polychlorinated biphenyls, methylmercury and other toxins which are found in some sources of fish, it is not recommended that women who are pregnant take excessive amounts of fish oil. Servings of fish should be limited to six ounces per week and they should refrain from using fish oil or other fatty acid supplement pills. Children should not consume more than two ounces of fish per week to avoid overexposure to these chemicals. Now you know although fish oil can benefit human beings a lot, fish oil side effects should never be neglected for the sake of your safety. 
Fish oil is oil derived from the tissues of oily fish. Fish oils contain the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), precursors of certain eicosanoids that are known to reduce inflammation in the body,[1][2] and have other health benefits, such as treating hypertriglyceridemia, although claims of preventing heart attacks or strokes have not been supported.[3][4][5][6] Fish oil and omega-3 fatty acids have been studied in a wide variety of other conditions, such as clinical depression,[7][8] anxiety,[9][10][11] cancer, and macular degeneration, yet benefits in these conditions have not been verified.[12]
Katzman  MA, Bleau  P, Blier  P,  et al; Canadian Anxiety Guidelines Initiative Group on behalf of the Anxiety Disorders Association of Canada/Association Canadienne des troubles anxieux and McGill University.  Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders.  BMC Psychiatry. 2014;14(suppl 1):S1. doi:10.1186/1471-244X-14-S1-S1PubMedGoogle ScholarCrossref
There are three types of omega-3 fatty acids, which include EPA, DHA and ALA, which is alpha-linoleic acid. Although EPA and DHA are found to have high amounts from animal sources, ALA is found in rich concentrations in plant sources, including certain vegetable oils and flaxseeds, although fatty fish and shellfish are the best sources of EPA and DHA, according to the National Center for Complementary and Alternative Medicine. Examples of these fatty fish and shellfish include salmon, tuna, trout, crab, oysters and mussels.
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.
People used to believe that osteoporosis and osteoarthritis were the result of aging and reduced intake of calcium and milk products. Science has now shown that these bone and joint disorders are, in part, due to inflammation. Because of this, bones and joints are prime targets for the anti-inflammatory properties of omega-3 oils from both fish and krill.
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.
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.
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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
Most U.S. adults fail to consume adequate amounts of foods rich in EPA and DHA on a regular basis (at least 8 ounces of fatty fish per week is recommended), and probably consume too many omega-6 fats in comparison (soybean oil, canola oil, cottonseed oil, etc.). This omega-3:omega-6 imbalance can have a negative effect on inflammation patterns and may also be implicated as a contributing factor to other processes related to cellular metabolism, hormone signaling, and even weight regulation.
Omega−3 fatty acids, also called ω−3 fatty acids or n−3 fatty acids,[1] are polyunsaturated fatty acids (PUFAs).[2][3] The fatty acids have two ends, the carboxylic acid (-COOH) end, which is considered the beginning of the chain, thus "alpha", and the methyl (-CH3) end, which is considered the "tail" of the chain, thus "omega". One way in which a fatty acid is named is determined by the location of the first double bond, counted from the tail, that is, the omega (ω-) or the n- end. Thus, in omega-3 fatty acids the first double bond is between the third and fourth carbon atoms from the tail end. However, the standard (IUPAC) chemical nomenclature system starts from the carboxyl end.
46. Gajos G, Rostoff P, Undas A, Piwowarska W. Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after pci to modify responsiveness to dual antiplatelet therapy) study. J Am Coll Cardiol. 2010;55:1671–8. [PubMed]

Tanaka, K., Ishikawa, Y., Yokoyama, M., Origasa, H., Matsuzaki, M., Saito, Y., Matsuzawa, Y., Sasaki, J., Oikawa, S., Hishida, H., Itakura, H., Kita, T., Kitabatake, A., Nakaya, N., Sakata, T., Shimada, K., and Shirato, K. Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: subanalysis of the JELIS trial. Stroke 2008;39(7):2052-2058. View abstract.
Thank you for your kind comment. As pointed out above, the main limitation of our meta-analysis is the heterogeneity, which we address several times in our main manuscript. We included studies with several different situations and participants with different underlying diseases, which would also result in wide heterogeneity in our meta-analysis. Based upon our post-hoc analysis, there was some common characteristics among the six trials with nominally significant results, including specific clinical diagnoses (5/6) and, placebo-control (4/6), which had also previously been addressed in our subgroup meta-analysis. Therefore, we suggested future placebo-controlled trials investigating the treatment effect of omega-3 in participants with specific clinical diagnoses should be warranted. In addition, improving underlying specific clinical diagnoses (5/6), good quality (placebo-control (4/6), low drop-out rate (zero in Exp/control groups: 4/6)), and long treatment duration (>= 12 weeks: 4/6) are all good indicators of high quality.
Other suspected health benefits of omega-3s and fish are less well established and need further study. They include suggestions of a reduced risk of breast cancer, colorectal cancer and possibly advanced prostate cancer, all related to eating fish rather than taking supplements. Some observational studies have associated omega-3s to a lower risk of cognitive decline, Alzheimer’s disease and dementia, as well as age-related macular degeneration.

Sangiovanni, J. P., Agron, E., Meleth, A. D., Reed, G. F., Sperduto, R. D., Clemons, T. E., and Chew, E. Y. {omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study. Am J Clin Nutr 2009;90(6):1601-1607. View abstract.
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