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).
If we want to deliver the benefits associated with EPA therapeutically, it is essential to optimise digestion and uptake. If we take EPA and DHA in their natural 1.5:1 ratio, it’s an uphill struggle for EPA because we know that DHA is more effectively absorbed and assimilated into cells. Delivering the benefits of EPA (for example, for cognitive function, mood and depression, inflammation regulation, heart health, skin health and so on), requires doses of EPA in excess of DHA, which determines the type of benefits obtained and the degree of the beneficial outcomes. The higher the ratio of EPA to DHA (meaning higher doses of EPA in relation to DHA), the more likely that EPA will be digested and absorbed, ready to meet the body’s high demands for this important nutrient.

Henneicke-von Zepelin, H. H., Mrowietz, U., Farber, L., Bruck-Borchers, K., Schober, C., Huber, J., Lutz, G., Kohnen, R., Christophers, E., and Welzel, D. Highly purified omega-3-polyunsaturated fatty acids for topical treatment of psoriasis. Results of a double-blind, placebo-controlled multicentre study. Br J Dermatol 1993;129(6):713-717. View abstract.
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.

Macchia, A., Levantesi, G., Franzosi, M. G., Geraci, E., Maggioni, A. P., Marfisi, R., Nicolosi, G. L., Schweiger, C., Tavazzi, L., Tognoni, G., Valagussa, F., and Marchioli, R. Left ventricular systolic dysfunction, total mortality, and sudden death in patients with myocardial infarction treated with n-3 polyunsaturated fatty acids. Eur.J.Heart Fail. 2005;7(5):904-909. View abstract.

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EPA and DHA are vital nutrients and may be taken to maintain healthy function of the following: brain and retina: DHA is a building block of tissue in the brain and retina of the eye. It helps with forming neural transmitters, such as phosphatidylserine, which is important for brain function. DHA is found in the retina of the eye and taking DHA may be necessary for maintaining healthy levels of DHA for normal eye function.
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. 

16. Saito Y, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, et al. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis. 2008;200:135–40. [PubMed]
The health benefits of fish oil include its ability to aid in weight loss and healthy pregnancy. It also promotes fertility and skin care (particularly for psoriasis and acne). It is beneficial in the treatment of various heart diseases, high cholesterol, depression, anxiety, ADHD, weak immune system, cancer, diabetes, inflammation, arthritis, IBD, AIDS, Alzheimer’s disease, eye disorders, macular degeneration, and ulcers.

What about blood clotting? Circulating cells called platelets are critical in causing your blood to clot. When platelets are activated, they aggregate and cause clots. If these clots occur in particularly sensitive regions of your body, they can lead to a heart attack or stroke. EPA reduces platelet activation, an early step in platelet aggregation to help to reduce clotting. One study found that EPA was superior to DHA in decreasing platelet activation, a precursor to blood clotting.1
In 1964 it was discovered that enzymes found in sheep tissues convert omega−6 arachidonic acid into the inflammatory agent called prostaglandin E2[71] which both causes the sensation of pain and expedites healing and immune response in traumatized and infected tissues.[72] By 1979 more of what are now known as eicosanoids were discovered: thromboxanes, prostacyclins, and the leukotrienes.[72] The eicosanoids, which have important biological functions, typically have a short active lifetime in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. If the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may, however, have deleterious effects.[72] Researchers found that certain omega−3 fatty acids are also converted into eicosanoids, but at a much slower rate. Eicosanoids made from omega−3 fatty acids are often referred to as anti-inflammatory, but in fact they are just less inflammatory than those made from omega−6 fats. If both omega−3 and omega−6 fatty acids are present, they will "compete" to be transformed,[72] so the ratio of long-chain omega−3:omega−6 fatty acids directly affects the type of eicosanoids that are produced.[72]
56. Davidson MH, Stein EA, Bays HE, et al. COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29:1354–1367. [PubMed]
In 2016, AHRQ reviewed 143 studies that evaluated the effects of giving omega-3 supplements to pregnant or breastfeeding women or giving formulas with added DHA to infants. They found that when women took omega-3 supplements during pregnancy, their babies’ birth weight was slightly higher, but the risk of an undesirably low birth weight did not change. Also, when women took omega-3 supplements during pregnancy, their pregnancies lasted a little longer, but there was no effect on the risk of premature birth. Omega-3s were not found to have effects on any other aspects of the mothers’ or infants’ health or the infants’ long-term development. Aspects of the infants’ health that were not shown to be affected by omega-3s include growth after birth, visual acuity, long-term neurological and cognitive development, and the risks of autism, ADHD, learning disorders, and allergies.

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.

Omega AD study, Irving et al. (54)	Double-blind, placebo-controlled, randomized	1741	DHA (1.7 g/d) and EPA (0.6 g/d) for 6 mo, then for all subjects (supplementation group and placebo group)	Supplementation was associated with positive weight gain and appetite in supplementation group at 6 mo, but not in the placebo group, and for both groups at 12 mo

Haberka, M., Mizia-Stec, K., Mizia, M., Janowska, J., Gieszczyk, K., Chmiel, A., Zahorska-Markiewicz, B., and Gasior, Z. N-3 polyunsaturated fatty acids early supplementation improves ultrasound indices of endothelial function, but not through NO inhibitors in patients with acute myocardial infarction: N-3 PUFA supplementation in acute myocardial infarction. Clin.Nutr. 2011;30(1):79-85. View abstract.
Fish oil is a commonly used dietary supplement, with sales in the U.S. alone reaching $976 million in 2009.[48] Problems of quality have been identified in periodic tests by independent researchers of marketed supplements containing fish oil and other marine oils. These problems include contamination, inaccurate listing of EPA and DHA levels, spoilage and formulation issues.[49]
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]
Fish Oil capsules contain omega-3 polyunsaturated fatty acids. Omega-3 polyunsaturated fatty acids are found in oils from certain types of fish, vegetables, and other plant sources. These fatty acids are not made by the body and must be consumed in the diet. Omega-3 polyunsaturated fatty acids work by lowering the body's production of triglycerides. High levels of triglycerides can lead to coronary artery disease, heart disease, and stroke.
Henriksen, C., Haugholt, K., Lindgren, M., Aurvag, A. K., Ronnestad, A., Gronn, M., Solberg, R., Moen, A., Nakstad, B., Berge, R. K., Smith, L., Iversen, P. O., and Drevon, C. A. Improved cognitive development among preterm infants attributable to early supplementation of human milk with docosahexaenoic acid and arachidonic acid. Pediatrics 2008;121(6):1137-1145. View abstract.
Findings  In this systematic review and meta-analysis of 19 clinical trials including 2240 participants from 11 countries, improvement in anxiety symptoms was associated with omega-3 polyunsaturated fatty acid treatment compared with controls in both placebo-controlled and non–placebo-controlled trials. The anxiolytic effects of omega-3 polyunsaturated fatty acids were also stronger in participants with clinical conditions than in subclinical populations.
Jump up ^ Heartney, Eleanor (2007). "Zhang Huan: Becoming the Body". Zhang Huan: Altered States. Charta and Asia Society. ISBN 978-8881586417. Retrieved 2014-10-23. This becomes abundantly clear in the work of Chinese body artist Zhang Huan. In the course of his career, Zhang Huan has subjected himself to painful trials: sitting motionless for hours in an outhouse covered in honey and fish oil while flies crawled over his body [...].
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.
Samsonov, M. A., Vasil'ev, A. V., Pogozheva, A. V., Pokrovskaia, G. R., Mal'tsev, G. I., Biiasheva, I. R., and Orlova, L. A. [The effect of a soy protein isolate and sources of polyunsaturated omega-3 fatty acids in an anti-atherosclerotic diet on the lipid spectrum of blood serum and immunological indicators in patients with ischemic heart disease and hypertension]. Vopr.Med Khim. 1992;38(5):47-50. View abstract.

Dangour, A. D., Allen, E., Elbourne, D., Fasey, N., Fletcher, A. E., Hardy, P., Holder, G. E., Knight, R., Letley, L., Richards, M., and Uauy, R. Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double-blind, controlled trial. Am.J.Clin.Nutr. 2010;91(6):1725-1732. View abstract.


Dry eye disease occurs when tears don’t provide enough moisture, causing eye discomfort and vision problems. Some studies show that getting more omega-3s from foods or supplements—mainly EPA and DHA—helps relieve symptoms of dry eye disease. But a large, recent study found that the symptoms of people with dry eye disease who took fish oil supplements of 2,000 mg EPA plus 1,000 mg DHA daily for 1 year did not improve any more than those who took a placebo (a dummy pill). More research on the effects of omega-3s on dry eye disease is needed.
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
Our scientists also focused on each oil’s freshness, measured by the degree of oxidation. Oxidation occurs in two phases: primary (measured by peroxide values) and secondary (measured by p-anisidine values). Total oxidation is formalized into a quantitative score, TOTOX. While Labdoor conducted tests of both primary and secondary oxidation, advances in rancidity testing confirm that added flavors–particularly added citrus flavors prevalent in liquid formulations–skew p-anisidine values and result in false positive outcomes. Until analytical techniques measuring p-anisidine values that are able to account for added flavors are established, Labdoor will use peroxide values as the primary indicator of freshness. All products recorded measurable levels of oxidation, with the average product recording a peroxide values of 3.7 meq/kg. 14/51 products recorded peroxide levels at or above the upper limit (10 meq/kg).

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.
Fish oil contains two very important omega-3 PUFAs. I’m talking about docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). DHA and EPA are sometimes called the marine omega-3s because they mainly come from fish. Some of the best fish to eat to obtain fish oil from in your diet include wild-caught salmon, herring, white fish, sardines and anchovies.
Scaly, itchy skin (eczema). Fish oil might help PREVENT eczema, but research is not consistent. Some early research suggests that mothers who take fish oil supplements during pregnancy reduce the risk of severe eczema in their infants. Also, population research suggests that children who eat fish at least once weekly from 1 to 2 years of age have a lower risk of developing eczema. But other research, including recent studies, suggests that neither supplementation during pregnancy nor supplementation during infancy reduces the risk of eczema. Overall, research suggests that fish oil does not help TREAT eczema once it has developed.
Chemical structure of alpha-linolenic acid (ALA), an essential omega−3 fatty acid, (18:3Δ9c,12c,15c, which means a chain of 18 carbons with 3 double bonds on carbons numbered 9, 12, and 15). Although chemists count from the carbonyl carbon (blue numbering), biologists count from the n (ω) carbon (red numbering). Note that, from the n end (diagram right), the first double bond appears as the third carbon-carbon bond (line segment), hence the name "n-3". This is explained by the fact that the n end is almost never changed during physiological transformations in the human body, as it is more energy-stable, and other compounds can be synthesized from the other carbonyl end, for example in glycerides, or from double bonds in the middle of the chain.
Participants treated with a daily dose of 2000 mg or more of omega-3 PUFAs showed a significantly greater association of treatment with reduced anxiety symptoms. In addition, participants receiving supplements containing less than 60% EPA showed a significant association, but not those receiving supplements containing 60% or more EPA. The depression literature supports the clinical benefits of EPA-enriched formulations (≥60% or ≥50%) compared with placebo for the treatment of clinical depression.9,13,73-75 This opposite effect of EPA-enriched formations on anxiety and depression is intriguing and possibly linked to a distinct underlying mechanism of omega-3 PUFAs. Exploration of the effects of omega-3 PUFAs on anxiety symptoms is just beginning and studies assessing the dose response anxiolytic effects of omega-3 PUFAs have not yet been performed. Further phase 2 trials of anxiety symptoms among participants with neuropsychiatric illness or physical illness should aim to determine the optimal dose.
To reach the required dose of EPA for treating certain conditions such as depression, CVD or CFS/ME you would need to take approximately 1-2 grams of ‘free EPA’ daily. Even with a concentrated omega-3 fish oil supplement, offering 180 mg excess EPA over DHA, this would require 10-20 capsules daily – significant in terms of volume and cost, and not efficient in terms of uptake in the body as our capacity for fat absorption is limited. The most effective and efficient way to ensure high EPA uptake in the body rapidly is to supplement with pure EPA for a minimum of 3-6 months.
All people need to consume omega-3 fats regularly. The recommended daily intake for adults is 1.6 grams for males  and 1.1 grams for females, according to the National Institutes of Health. The omega-3 family encompasses numerous fatty acids, but three primary forms are eicosapentaenoic acid, docosahexaenoic acid, and alpha-linolenic acid. The first two forms primarily occur in fish, such as salmon, mackerel, and tuna. The third can be found in plant oils, including flaxseed, soybean, walnut, and canola oils.
Subgroup meta-analysis of the anxiolytic effects of omega-3 polyunsaturated fatty acids (PUFAs) based on different EPA percentages. The anxiolytic effects of omega-3 PUFAs were significant in the subgroup with an EPA percentage less than 60% (k, 11; Hedges g = 0.485; 95% CI, 0.017 to 0.954; P = .04) but not significant in the subgroups with an EPA percentage of at least 60% (k, 9; Hedges g, 0.092; 95% CI, –0.102 to 0.285; P = .35).
Although GOED has used diligent care to ensure that the information provided on this website is accurate and up to date, we make no representation or warranty of the accuracy, reliability or completeness of this information. The website is intended to educate and inform readers about omega-3 fatty acids and is not meant to constitute or provide medical advice, diagnosis or treatment and is distributed without warranty of any kind, either expressly or implied. In no event shall GOED be liable for any damages arising from the reader’s reliance upon, or use of, these materials. The reader shall be solely responsible for any interpretation or use of material contained herein. The content of this document is subject to change without further notice.
Kabir, M., Skurnik, G., Naour, N., Pechtner, V., Meugnier, E., Rome, S., Quignard-Boulange, A., Vidal, H., Slama, G., Clement, K., Guerre-Millo, M., and Rizkalla, S. W. Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am.J.Clin.Nutr. 2007;86(6):1670-1679. View abstract.
Irving, G. F., Freund-Levi, Y., Eriksdotter-Jonhagen, M., Basun, H., Brismar, K., Hjorth, E., Palmblad, J., Vessby, B., Vedin, I., Wahlund, L. O., and Cederholm, T. Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer's disease: the omega-3 Alzheimer's disease study. J Am Geriatr Soc 2009;57(1):11-17. View abstract.

Fish oil combined with fenofibrate has not been studied extensively in randomized controlled trials. Data to date, however, suggest that the combination is safe and effective.63,64 A recent randomized controlled trial of 100 patients with severe hypertriglyceridemia and HIV on highly active antiretroviral therapy showed that a regimen of fenofibrate and 3 g/d of fish oil for 8 weeks was well tolerated. The median baseline triglyceride level of 650 mg/dL was reduced by 65%.63 Another recent randomized, 2 month, double-blind, placebo-controlled trial, which was set up to assess the safety and efficacy of fenofibrate with 4 g of fish oil, showed that in the 81 patients assigned to combination therapy, triglyceride levels were reduced by 61%. Therapy was well-tolerated without significant adverse reactions at 8 weeks or at the end of a 2-year open label extension.64 The combination of fish oil and niacin requires further study.
Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.
First difference is in the area of omega-6 fatty acid metabolism. Whereas EPA is the inhibitor of the enzyme (D5D) that directly produces AA, DHA is an inhibitor of another key enzyme delta-6-desaturase (D6D) that produces the first metabolite from linoleic acid known as gamma linolenic acid or GLA (6). However, this is not exactly an advantage. Even though reduction of GLA will eventually decrease AA production, it also has the more immediate effect of reducing the production of the next metabolite known as dihomo gamma linolenic acid or DGLA. This can be a disaster as a great number of powerful anti-inflammatory eicosanoids are derived from DGLA. This is why if you use high-dose DHA it is essential to add back trace amounts of GLA to maintain sufficient levels of DGLA to continue to produce anti-inflammatory eicosanoids.
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).
In general, most health organizations agree 250–500 milligrams of EPA and DHA combined each day is a reasonable amount to support healthy individuals. However, people with heart problems (or those with a high risk of heart disease), depression, anxiety and cancer (and possibly more conditions) may benefit from higher doses — up to 4,000 milligrams per day for some heart-related conditions. (5)
In a study published after the AHRQ report, scientists in Denmark gave high-dose fish oil supplements or placebos to 736 pregnant women during the third trimester of pregnancy. Children born to mothers who had taken fish oil were less likely to develop asthma or persistent wheezing in early childhood, and this was most noticeable in children whose mothers had low blood levels of EPA and DHA before they started to take the supplements. However, other studies that evaluated the effects of omega-3 supplementation during pregnancy on childhood asthma risk have had inconsistent results.
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]
Further, according to subgroup results based on the presence of specific clinical diagnoses or not, the association of omega-3 PUFA treatment with reduced anxiety symptoms was significantly higher in subgroups with specific clinical diagnoses than in subgroups without clinical conditions. Among 6 studies included in a meta-analysis of the effect of omega-3 PUFAs on depressive symptoms, the analysis showed a nearly null effect of omega-3 PUFAs on depressive symptoms in healthy participants.73 Although the reason for the null effect of omega-3 PUFAs on anxiety and depressive symptoms remains unclear, certain pathophysiological conditions might be required for omega-3 PUFAs to exert an association of treatment with reduced anxiety symptoms.
A six week, double-blind study on fish oil supplementation for body composition showed that the group taking 4 grams/day of fish oil (contained 1600mg if EPA & 800mg of DHA) experienced a significant increase in lean body mass and significant decrease in fat mass compared to a group that took safflower oil (an omega-6 oil). The fish oil group also saw a tendency for decreases in cortisol, a hormone associated with belly fat gain when elevated.
In short, there is no single optimal EPA:DHA ratio. If we are really healthy, with an optimal omega-6 to omega-3 ratio (from a diet rich in omega-3 fatty acids and low in grains and vegetable oils) and have an active, stress-free lifestyle, relying on standard fish oil in the natural 1.5:1 EPA:DHA ratio or simply consuming oily fish is completely adequate.

Omega−3 fatty acids are important for normal metabolism.[8] Mammals are unable to synthesize omega−3 fatty acids, but can obtain the shorter-chain omega−3 fatty acid ALA (18 carbons and 3 double bonds) through diet and use it to form the more important long-chain omega−3 fatty acids, EPA (20 carbons and 5 double bonds) and then from EPA, the most crucial, DHA (22 carbons and 6 double bonds).[8] The ability to make the longer-chain omega−3 fatty acids from ALA may be impaired in aging.[9][10] In foods exposed to air, unsaturated fatty acids are vulnerable to oxidation and rancidity.[11]

Fish oil supplements have been promoted as easy way to protect the heart, ease inflammation, improve mental health, and lengthen life. Such claims are one reason why Americans spend more than $1 billion a year on over-the-counter fish oil. And food companies are adding it to milk, yogurt, cereal, chocolate, cookies, juice, and hundreds of other foods.
Egert, S., Somoza, V., Kannenberg, F., Fobker, M., Krome, K., Erbersdobler, H. F., and Wahrburg, U. Influence of three rapeseed oil-rich diets, fortified with alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid on the composition and oxidizability of low-density lipoproteins: results of a controlled study in healthy volunteers. Eur J Clin Nutr 2007;61(3):314-325. View abstract.
Keck, P. E., Jr., Mintz, J., McElroy, S. L., Freeman, M. P., Suppes, T., Frye, M. A., Altshuler, L. L., Kupka, R., Nolen, W. A., Leverich, G. S., Denicoff, K. D., Grunze, H., Duan, N., and Post, R. M. Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Biol.Psychiatry 11-1-2006;60(9):1020-1022. View abstract.
A study in 2013, (Stafford, Jackson, Mayo-Wilson, Morrison, Kendall), stated the following in its conclusion: "Although evidence of benefits for any specific intervention is not conclusive, these findings suggest that it might be possible to delay or prevent transition to psychosis. Further research should be undertaken to establish conclusively the potential for benefit of psychological interventions in the treatment of people at high risk of psychosis."`[56]
In fact, fish oil is even dipping its way into mainstream medicine. In September 2018, Amarin Corporation, the biopharmaceutical developer of pharmaceutical-grade fish oil Vascepa, released preliminary findings of its double-blind clinical trial. In the study, researchers tracked more than 8,000 adults for a median 4.9 years. The mix of study participants had either established cardiovascular disease or type 2 diabetes and another cardiovascular disease risk factor, along with persistently elevated triglycerides.
It’s uncertain whether omega-3 fatty acid supplements are helpful for depression. Although some studies have had promising results, a 2015 evaluation of 26 studies that included more than 1,400 people concluded that if there is an effect, it may be too small to be meaningful. Other analyses have suggested that if omega-3s do have an effect, EPA may be more beneficial than DHA and that omega-3s may best be used in addition to antidepressant medication rather than in place of it. 
Further, according to subgroup results based on the presence of specific clinical diagnoses or not, the association of omega-3 PUFA treatment with reduced anxiety symptoms was significantly higher in subgroups with specific clinical diagnoses than in subgroups without clinical conditions. Among 6 studies included in a meta-analysis of the effect of omega-3 PUFAs on depressive symptoms, the analysis showed a nearly null effect of omega-3 PUFAs on depressive symptoms in healthy participants.73 Although the reason for the null effect of omega-3 PUFAs on anxiety and depressive symptoms remains unclear, certain pathophysiological conditions might be required for omega-3 PUFAs to exert an association of treatment with reduced anxiety symptoms.
For example, large predatory fish like shark, swordfish, king mackerel, tilefish and albacore tuna can contain high levels of methyl mercury, a toxin that would override any health benefit, especially for the developing brains of fetuses and young children as well as for adults, Dr. Nesheim and Marion Nestle, professor emerita of nutrition, food studies and public health at New York University, noted in 2014 in an editorial in the American Journal of Clinical Nutrition. (Levels of mercury and other contaminants in fish have since declined somewhat but are not negligible.)
Protects Vision: Our eyes' retinas are a membranous structures and the whole eye is covered in a soft double layer of membranes, making your eyes' health dependent on the liver (who knew?). The liver helps metabolize fat-soluble vitamins that feed and maintain those membranes. If you're deficient in DHA, it affects how we see by delaying the system that converts light into neural energy in the retina.

Several studies confirmed the benefit of omega-3 supplementation during pregnancy in terms of proper development of the brain and retina. Of the 2 most important long-chain omega-3 fatty acids, EPA and DHA, DHA is the more important for proper cell membrane function and is vital to the development of the fetal brain and retina (17). During the third trimester, vast amounts of DHA accumulate in fetal tissue (20). The 2 most infiltrated fetal areas include the retina and brain, which may correlate with normal eyesight and brain function (19). A study by Judge et al. (20) found that children whose mothers had taken DHA supplementation during pregnancy (n = 29) had significantly better problem-solving skills at 9 mo old (P = 0.017) than those whose mothers had not taken DHA supplementation during pregnancy (n = 15). Another study provided a cognitive assessment of children 2.5 y after maternal EPA+DHA supplementation during pregnancy from 20 wk of gestation until delivery (n = 33) compared with children in a placebo group (n = 39). Children in the EPA + DHA–supplemented group attained significantly higher scores for eye and hand coordination [mean score, 114 (SD 10.2] than those in the placebo group [mean score, 108 (SD 11.3)] (P = 0.021, adjusted P = 0.008) (19).
So back to fish oil in general. The major fish oil benefits include decreasing the risk of heart disease and stroke while also helping reduce symptoms of depression, hypertension, attention deficit hyperactivity disorder (ADHD), joint pain, arthritis and chronic skin ailments like eczema. (2) Fish oil intake has also been associated with aiding the body in weight loss, fertility, pregnancy and increased energy. Prescription fish oil has even been approved by the FDA to lower unhealthy high triglyceride levels. (3)
Macchia, A., Levantesi, G., Franzosi, M. G., Geraci, E., Maggioni, A. P., Marfisi, R., Nicolosi, G. L., Schweiger, C., Tavazzi, L., Tognoni, G., Valagussa, F., and Marchioli, R. Left ventricular systolic dysfunction, total mortality, and sudden death in patients with myocardial infarction treated with n-3 polyunsaturated fatty acids. Eur.J.Heart Fail. 2005;7(5):904-909. View abstract.
The omega-3 PUFA EPA and DHA are important throughout life and are a dietary necessity found predominantly in fish and fish-oil supplements. The omega-3 fatty acids EPA and DHA are essential for proper fetal development, and supplementation during pregnancy has also been linked to decreased immune responses in infants including decreased incidence of allergies in infants. Omega-3 fatty acid consumption has been associated with improved cardiovascular function in terms of antiinflammatory properties, PAD, reduced major coronary events, and improved antiplatelet effects in the face of aspirin resistance or clopidogrel hyporesponsiveness. Patients with AD have been shown to be deficient in DHA, and supplementing them with EPA+DHA not only reverses this deficiency, but may also improve cognitive functioning in patients with very mild AD. With increasing rates of pediatric allergies, cardiovascular disease, and AD in the United States, EPA and DHA may be a safe and inexpensive link to a healthier life. Further research should be conducted in humans to assess a variety of clinical outcomes including quality of life and mental status. In addition, because potent lipid mediator metabolites of EPA and DHA are of great interest currently, their influence on these important outcomes should be assessed because current evidence suggests that their antiinflammatory and tissue-protective effects are nearly 1000 times greater than those of EPA and DHA (7).
For rheumatoid arthritis, one systematic review found consistent, but modest, evidence for the effect of marine n−3 PUFAs on symptoms such as "joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity" as well as the use of non-steroidal anti-inflammatory drugs.[35] The American College of Rheumatology has stated that there may be modest benefit from the use of fish oils, but that it may take months for effects to be seen, and cautions for possible gastrointestinal side effects and the possibility of the supplements containing mercury or vitamin A at toxic levels. The National Center for Complementary and Integrative Health has concluded that "[n]o dietary supplement has shown clear benefits for rheumatoid arthritis", but that there is preliminary evidence that fish oil may be beneficial, but needs further study.[36]
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]

Research conducted by Professor Peter Howe at the University of South Australia has shown that fish oil improves the efficacy of exercise in attempts to reduce weight. Volunteers who were given fish oil in their diet showed greater weight loss as compared to those who did not regularly consume it. Fish oil contains omega-3 fatty acids, which help to promote the weight loss, so a combination of physical workout and intake of this oil helps in reducing body fat significantly faster.
Aceite de Pescado, Acides Gras Oméga-3, Acides Gras Oméga 3, Acides Gras Oméga 3 Sous Forme Ester Éthylique, Acides Gras N-3, Acides Gras Polyinsaturés N-3, Acides Gras W3, ACPI, EPA/DHA Ethyl Ester, Ester Éthylique de l'AEP/ADH, Fish Body Oil, Herring Oil, Huile de Foie de Morue, Huile de Hareng, Huile de Menhaden, Huile de Poisson, Huile de Saumon, Huile de Thon, Huile Lipidique Marine, Huile Marine, Huiles Marines, Lipides Marins, Marine Lipid Concentrate, Marine Fish Oil, Marine Lipid Oil, Marine Lipids, Marine Oil, Marine Oils, Marine Triglyceride, Menhaden Oil, N-3 Fatty Acids, N3-polyunsaturated Fatty Acids, Omega 3, Oméga 3, Omega-3, Oméga-3, Omega-3 Fatty Acid Ethyl Ester, Omega-3 Fatty Acids, Omega 3 Fatty Acids, Omega-3 Marine Triglycerides, PUFA, Salmon Oil, Triglycérides Marins, Tuna Fish Oil, Tuna Oil, W-3 Fatty Acids.
The absence of DHA in many pure EPA trials, and therefore lack of competition between EPA and DHA during digestion and consequently for uptake, is considered to be partly responsible for the positive outcomes. Simply put, pure EPA delivers more EPA into cells where it is needed than combined EPA & DHA blends. Consequently, oils containing DHA may not be suitable for a variety of conditions when treatment relies on increasing levels of EPA and its end products.
Bo and I worked with Dr. Harris many years ago to measure the impact of eating one Omega Cookie® daily on the study participants’ omega-3 index levels, and we recently ran into him at ISFFAL. At the conference, we remeasured our omega-3 index and omega-6/omega-3 ratios, and a few weeks later, we got our results in the mail. For the two of us, it was exciting to get another concrete measure of how our daily omega-3 consumption impacted our scores. For the record, we take one vial of Omega Restore™ per night and frequently sneak an Omega Heaven® or Omega Cookie during the day.
Because patients with depression experience rapid shrinking of their hippocampus, many strategies for relieving depression focus on increasing new brain cell growth in that specific area of the brain.23 There’s now evidence that increasing omega-3 intake, especially DHA, may be an effective way of treating or preventing depression, partly by protecting the hippocampus from further shrinkage.23
A six week, double-blind study on fish oil supplementation for body composition showed that the group taking 4 grams/day of fish oil (contained 1600mg if EPA & 800mg of DHA) experienced a significant increase in lean body mass and significant decrease in fat mass compared to a group that took safflower oil (an omega-6 oil). The fish oil group also saw a tendency for decreases in cortisol, a hormone associated with belly fat gain when elevated.
Bo and I worked with Dr. Harris many years ago to measure the impact of eating one Omega Cookie® daily on the study participants’ omega-3 index levels, and we recently ran into him at ISFFAL. At the conference, we remeasured our omega-3 index and omega-6/omega-3 ratios, and a few weeks later, we got our results in the mail. For the two of us, it was exciting to get another concrete measure of how our daily omega-3 consumption impacted our scores. For the record, we take one vial of Omega Restore™ per night and frequently sneak an Omega Heaven® or Omega Cookie during the day.
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]
A group out of India conducted a study published in Cancer Chemotherapy and Pharmacology based on the premise that “fish oil rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize tumor cells to anti-cancer drugs.” The study found that using 5-Fluorouracil (5-FU) to treat colorectal cancer along with fish oil increased the survival rate in carcinogen-treated animals. Researchers also found that the fish oil ameliorated hematologic depression, along with gastrointestinal, hepatic and renal toxicity caused by the 5-FU. (15)
The effect of fish oil on incident atrial fibrillation has not been studied in large randomized trials, and observational population-based trials show mixed results. The Danish Diet, Cancer and Health Study, and the Rotterdam Study followed 47,000 and 5100 middle-aged adults, respectively.45,46 Neither study found that the consumption of fish oil affected the incidence of atrial fibrillation. Similar findings were seen in the Women’s Health Initiative where there was no association between fish and omega-3 FA intake regarding incident atrial fibrillation.47 However, in a 12-year prospective, observational study of 4815 adults over the age of 65, daily fish consumption was associated with a 31% risk reduction in incident atrial fibrillation.48

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).
An excessive dosage of fish oil can have adverse allergies and side effects on the body. Furthermore, fish oil can be problematic if you have certain conditions so it is necessary to consume fish oil supplements cautiously. Moreover, it can be consumed in various forms. These include eating the fish directly by baking, roasting, frying, grilling, broiling, or smoking it. It can also be consumed in the form of concentrated dietary supplements like liquid, tablet, capsule, pill, or soft gels. Also, there are various pharmaceutical grades of the oil. It is not necessary to constantly consume pharmaceutical-grade oil or even supplements. You should also consult your doctor to confirm the mode of consuming fish oil and the overall need for it in your diet.
Could you be deficient in omega-3s? The University of Maryland Medical Center says that the symptoms “include fatigue, poor memory, dry skin, heart problems, mood swings or depression, and poor circulation.” They also warn against a poor omega-3 to omega-6 ratio, cautioning readers that it may be “associated with worsening inflammation over time.” (6)
The effect of fish oil on incident atrial fibrillation has not been studied in large randomized trials, and observational population-based trials show mixed results. The Danish Diet, Cancer and Health Study, and the Rotterdam Study followed 47,000 and 5100 middle-aged adults, respectively.45,46 Neither study found that the consumption of fish oil affected the incidence of atrial fibrillation. Similar findings were seen in the Women’s Health Initiative where there was no association between fish and omega-3 FA intake regarding incident atrial fibrillation.47 However, in a 12-year prospective, observational study of 4815 adults over the age of 65, daily fish consumption was associated with a 31% risk reduction in incident atrial fibrillation.48
Fish oil is a commonly used dietary supplement, with sales in the U.S. alone reaching $976 million in 2009.[48] Problems of quality have been identified in periodic tests by independent researchers of marketed supplements containing fish oil and other marine oils. These problems include contamination, inaccurate listing of EPA and DHA levels, spoilage and formulation issues.[49]
The health benefits of fish oil can be incredible for the body’s largest organ, the skin. This source of essential fats improves the health and beauty of human skin in several ways. Fish oil benefits and nourishes the skin with fats and contributes fat-soluble vitamins that help skin maintain a smooth, elastic texture. There is also evidence that fish oil prevents wrinkles and works against the aging process.
Human studies also confirm cognition and memory improvement with omega-3 supplementation. For example, a study showed that both fish oil and krill oil enhanced cognitive function in a group of older men by increasing oxygen delivery to their brains. Interestingly, for those taking krill oil this effect was more prominent than those taking fish oil, though both groups were significantly better than placebo.30 As we pointed out earlier, because the omega-3 DHA is bound to phospholipids in krill it may be more effectively incorporated into the critical cell membrane in brain cells.
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]

Agency for Healthcare Research and Quality. Effects of Omega-3 Fatty Acids on Lipids and Glycemic Control in Type II Diabetes and the Metabolic Syndrome and on Inflammatory Bowel Disease, Rheumatoid Arthritis, Renal Disease, Systemic Lupus Erythematosus, and Osteoporosis. AHRQ Publication No. 04-E012-1; 2004. Available at: https://archive.ahrq.gov/downloads/pub/evidence/pdf/o3lipid/o3lipid.pdf. (Accessed February 7, 2017).

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