^ Jump up to: a b c Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, Geleijnse JM, Rauch B, Ness A, Galan P, Chew EY, Bosch J, Collins R, Lewington S, Armitage J, Clarke R (March 2018). "Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals". JAMA Cardiology. 3 (3): 225–34. doi:10.1001/jamacardio.2017.5205. PMC 5885893. PMID 29387889.


Results of studies investigating the role of LCPUFA supplementation and LCPUFA status in the prevention and therapy of atopic diseases (allergic rhinoconjunctivitis, atopic dermatitis and allergic asthma) are controversial; therefore, at the present stage of our knowledge (as of 2013) we cannot state either that the nutritional intake of n−3 fatty acids has a clear preventive or therapeutic role, or that the intake of n-6 fatty acids has a promoting role in context of atopic diseases.[64]
Gajos G1, Rostoff P, Undas A, et al. 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 Apr 20;55(16):1671-8. View abstract.
Marine and freshwater fish oil vary in contents of arachidonic acid, EPA and DHA.[15] The various species range from lean to fatty and their oil content in the tissues has been shown to vary from 0.7% to 15.5%.[16] They also differ in their effects on organ lipids.[15] Studies have revealed that there is no relation between total fish intake or estimated omega−3 fatty acid intake from all fish, and serum omega−3 fatty acid concentrations.[17] Only fatty fish intake, particularly salmonid, and estimated EPA + DHA intake from fatty fish has been observed to be significantly associated with increase in serum EPA + DHA.[17]
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.
The three types of omega-3s are APA, EPA and DHA. The first is a medium-chain fatty acid and must be converted into EPA before being synthesized by the body, and only about 1 percent of the APA consumed is able to be converted. EPA and DHA are already in a form ready to be synthesized (and are the subject of most scientific research regarding omega-3s).
Omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential nutrients that have potential preventive and therapeutic effects on psychiatric disorders, such as anxiety and depression,7-15 as well as comorbid depression and anxiety in physically ill patients,16-19 patients with coronary heart disease,20,21 and pregnant women.22,23 Preclinical data support the effectiveness of omega-3 PUFAs as treatment for anxiety disorders. Song et al24,25 found that an EPA-rich diet could reduce the development of anxiety-like behaviors in rats as well as normalize dopamine levels in the ventral striatum. In addition, Yamada et al26 showed that a high dietary omega-3 to omega-6 PUFA ratio reduced contextual fear behaviors in mice and that these effects were abolished by a cannabinoid CB1 receptor antagonist.

The U.S. Food and Drug Administration recommends consuming no more than 3 g/day of EPA and DHA combined, including up to 2 g/day from dietary supplements. Higher doses are sometimes used to lower triglycerides, but anyone taking omega-3s for this purpose should be under the care of a healthcare provider because these doses could cause bleeding problems and possibly affect immune function. Any side effects from taking omega-3 supplements in smaller amounts are usually mild. They include an unpleasant taste in the mouth, bad breath, heartburn, nausea, stomach discomfort, diarrhea, headache, and smelly sweat.

A 2014 meta-analysis of eleven trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and of eight trials with patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo. The study concluded that: "The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD."[42]
Added inactive ingredients also contribute to product safety. Eight supplements in this study contained ‘natural’ flavors such as citrus-derived additives. One product, Coromega Omega-3, also contained benzoic acid, a popular antibacterial agent linked to carcinogenic risks when combined with vitamin C. Other controversial excipients included the artificial coloring agents FD&C Blue 1 and FD&C Red 40 as well as the whitening agent titanium dioxide.
“This systematic review did find moderate evidence that ALA, found in plant oils (such as rapeseed or canola oil) and nuts (particularly walnuts) may be slightly protective of some diseases of the heart and circulation. However, the effect is very small, 143 people would need to increase their ALA intake to prevent one person developing arrhythmia. One thousand people would need to increase their ALA intake to prevent one person dying of coronary heart disease or experiencing a cardiovascular event.  ALA is an essential fatty acid, an important part of a balanced diet, and increasing intakes may be slightly beneficial for prevention or treatment of cardiovascular disease."
Ramakrishnan, U., Stein, A. D., Parra-Cabrera, S., Wang, M., Imhoff-Kunsch, B., Juarez-Marquez, S., Rivera, J., and Martorell, R. Effects of docosahexaenoic acid supplementation during pregnancy on gestational age and size at birth: randomized, double-blind, placebo-controlled trial in Mexico. Food Nutr Bull 2010;31(2 Suppl):S108-S116. View abstract.
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.
A report by the Harvard Medical School studied five popular brands of fish oil, including Nordic Ultimate, Kirkland and CVS. They found that the brands had "negligible amounts of mercury, suggesting either that mercury is removed during the manufacturing of purified fish oil or that the fish sources used in these commercial preparations are relatively mercury-free".[66]

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).
Three omega−3 fatty acids are important in human physiology, α-linolenic acid (18:3, n-3; ALA), eicosapentaenoic acid (20:5, n-3; EPA), and docosahexaenoic acid (22:6, n-3; DHA).[67] These three polyunsaturates have either 3, 5, or 6 double bonds in a carbon chain of 18, 20, or 22 carbon atoms, respectively. As with most naturally-produced fatty acids, all double bonds are in the cis-configuration, in other words, the two hydrogen atoms are on the same side of the double bond; and the double bonds are interrupted by methylene bridges (-CH
EPA and DHA  stand for eicosapentaenoic acid and docosahexaenoic acid respectively. These fatty acids are omega-3 fats, which are found in cold water fish. EPA DHA are highly unsaturated fats because they contain six and five double bonds on their long structural chains. These polyunsaturated fats play a very important role with the function of our bodies.
^ Jump up to: a b Casula M, Soranna D, Catapano AL, Corrao G (August 2013). "Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: A meta-analysis of randomized, placebo controlled trials [corrected]". Atherosclerosis. Supplements. 14 (2): 243–51. doi:10.1016/S1567-5688(13)70005-9. PMID 23958480.
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.

(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.)
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.
It is great for improving the condition of the dry skin by making it look shiny and vibrant. It is useful in treating various skin problems such as eczema, psoriasis, itching, skin redness, skin lesions, and rashes. In terms of psoriasis, the EPA present in fish oil restricts the growth of pro-inflammatory agents by producing arachidonic acid. Therefore, fish oil can also be applied topically to get relief from psoriasis.
The studies recruited men and women, some healthy and others with existing illnesses from North America, Europe, Australia and Asia. Participants were randomly assigned to increase their omega 3 fats or to maintain their usual intake of fat for at least a year. Most studies investigated the impact of giving a long-chain omega 3 supplement in a capsule form and compared it to a dummy pill.  Only a few assessed whole fish intake. Most ALA trials added omega 3 fats to foods such as margarine and gave these enriched foods, or naturally ALA-rich foods such as walnuts, to people in the intervention groups, and usual (non-enriched) foods to other participants.
Schilling, J., Vranjes, N., Fierz, W., Joller, H., Gyurech, D., Ludwig, E., Marathias, K., and Geroulanos, S. Clinical outcome and immunology of postoperative arginine, omega-3 fatty acids, and nucleotide-enriched enteral feeding: a randomized prospective comparison with standard enteral and low calorie/low fat i.v. solutions. Nutrition 1996;12(6):423-429. View abstract.
We hypothesized that omega-3 PUFAs might have anxiolytic effects in patients with significant anxiety- and fear-related symptoms. However, there have been no systematic reviews of this topic to date. Thus, we examined the anxiolytic effects of omega-3 PUFAs in participants with elevated anxiety symptoms in the results of clinical trials to determine the overall efficacy of omega-3 PUFAs for anxiety symptoms irrespective of diagnosis.
Fish oil is FDA approved to lower triglycerides levels, but it is also used for many other conditions. It is most often used for conditions related to the heart and blood system. Some people use fish oil to lower blood pressure, triglycerides and cholesterol levels. Fish oil has also been used for preventing heart disease or stroke, as well as for clogged arteries, chest pain, irregular heartbeat, bypass surgery, heart failure, rapid heartbeat, preventing blood clots, and high blood pressure after a heart transplant.
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