Bemelmans, W. J., Broer, J., Feskens, E. J., Smit, A. J., Muskiet, F. A., Lefrandt, J. D., Bom, V. J., May, J. F., and Meyboom-de Jong, B. Effect of an increased intake of alpha-linolenic acid and group nutritional education on cardiovascular risk factors: the Mediterranean Alpha-linolenic Enriched Groningen Dietary Intervention (MARGARIN) study. Am J Clin Nutr 2002;75(2):221-227. View abstract.
Since 2004, scientists have been suggesting that the omega-3 index be used as a way to measure a person’s risk of cardiovascular disease, in a similar way to how cholesterol levels are used today (1). A recent study funded by the National Institutes for Health even indicated that the omega-3 index could be a better predictor of death risk than serum cholesterol levels (2).

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.


So why is an excess of DHA detrimental and an excess of EPA useful? DHA has a larger structure with two extra carbons and two extra double bonds, so it literally takes up more space in cell membranes than EPA. On the one hand, this is important because DHA plays a structural role in maintaining the fluidity of cell membranes ( essential for the normal function of proteins, channels and receptors that are also embedded in the membrane), but if a cell membrane becomes too saturated with DHA it can become too fluid, which can have a negative effect on cell function. EPA, on the other hand, is constantly utilised and always in demand.
Omega-3s are generally safe and well tolerated. Stomach upset and “fishy taste” have been the most common complaints, but they are less frequent now thanks to manufacturing methods that reduce impurities. Past concerns about omega-3s increasing the risk of bleeding have been largely disproven, but caution is still advised in people taking blood thinners or who are about to undergo surgery. As mentioned, caution is needed in people with bipolar disorder to prevent cycling to mania. Because omega-3s are important to brain development, and pregnancy depletes omega-3 in expectant mothers, supplementation should theoretically benefit pregnant women and their children. Fish consumption in pregnancy is supported by the FDA, but because we do not have long-term data on safety or optimal dosing of omega-3s in pregnancy, expectant mothers should consider omega-3 supplements judiciously.

The question is whether the observed cardiovascular benefits often found among fish eaters is due solely to the oils in fish or to some other characteristics of seafood or to still other factors common to those who eat lots of fish, like eating less meat or pursuing a healthier lifestyle over all. Whatever the answer, it does not seem to be fish oil supplements.
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
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
Another study conducted by researchers at Rhode Island Hospital examined the relationship between fish oil supplementation and indicators of cognitive decline. The subjects of the study were older adults: 229 cognitively normal individuals, 397 patients with mild cognitive impairment and 193 patients with Alzheimer’s disease. They were assessed with neuropsychological tests and brain magnetic resonance imaging every six months while taking fish oil supplements. The study found that the adults taking fish oil (who had not yet developed Alzheimer’s and did not have genetic risk factor for developing Alzheimer’s known as APOE ε4) experienced significantly less cognitive decline and brain shrinkage than adults not taking fish oil. (9)
My estimate is that close to 90 percent of fish oils on the market today may contain mercury and pesticide residues plus hydrogenated oils. Of course, this is my opinion based on my own research from visiting different manufacturing plants, interviewing companies, and studying the research and the listed ingredients of typical fish oils. I would stay away from ALL fish oils that do not have antioxidants like astaxanthin, which help stabilize the oil from going rancid. I always look for astaxanthin as part of any high-quality fish oil supplement.
The way that fish oil does that is to interfere with carbohydrate metabolism, and in insulin-resistant people or in people with specific genetic differences that might predispose them to having very high triglycerides, you do benefit from interfering that pathway with the fish oil, but I would actually try a low-carbohydrate diet in a lot of those situations to see if that helps with lowering triglycerides, or in the case of insulin resistance, I would try to address the insulin resistance at its root cause.
Scientific studies have found that fish oil can help to prevent and kill various cancers, including colon, prostate and breast. (13a) Not only has research proven that it makes conventional cancer drugs more effective, but it’s also an effective stand-alone therapy in natural cancer treatment. Intravenous fish oil lipid emulsions, in particular, are rich in omega-3 polyunsaturated fatty acids, which exhibit anti-inflammatory and immunomodulatory effects. (13b)
So why is an excess of DHA detrimental and an excess of EPA useful? DHA has a larger structure with two extra carbons and two extra double bonds, so it literally takes up more space in cell membranes than EPA. On the one hand, this is important because DHA plays a structural role in maintaining the fluidity of cell membranes ( essential for the normal function of proteins, channels and receptors that are also embedded in the membrane), but if a cell membrane becomes too saturated with DHA it can become too fluid, which can have a negative effect on cell function. EPA, on the other hand, is constantly utilised and always in demand.
Norris, J. M., Yin, X., Lamb, M. M., Barriga, K., Seifert, J., Hoffman, M., Orton, H. D., Baron, A. E., Clare-Salzler, M., Chase, H. P., Szabo, N. J., Erlich, H., Eisenbarth, G. S., and Rewers, M. Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes. JAMA 9-26-2007;298(12):1420-1428. View abstract.
Harper, M., Thom, E., Klebanoff, M. A., Thorp, J., Jr., Sorokin, Y., Varner, M. W., Wapner, R. J., Caritis, S. N., Iams, J. D., Carpenter, M. W., Peaceman, A. M., Mercer, B. M., Sciscione, A., Rouse, D. J., Ramin, S. M., and Anderson, G. D. Omega-3 fatty acid supplementation to prevent recurrent preterm birth: a randomized controlled trial. Obstet Gynecol 2010;115(2 Pt 1):234-242. View abstract.
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]
First, always remember that it’s the omega-3s that count. When making your purchase, be sure to determine the amount of omega-3s per serving. Many doctors often recommend 1000 to 1200 mg of fish oil because that amount of fish oil contains the total amount of omega-3s the doctor wants you to consume. 1000 mg or 1200 mg of fish oil doesn’t equal 1000 or 1200 mg of omega-3s. A standard 1000 mg fish oil softgel provides around 300 mg of omega-3s (and even less of the important EPA and DHA), and to meet the 500 mg EPA and DHA recommendation, a minimum of two softgels would be necessary. Make sure to read the “Supplement Facts” label to determine the amount of EPA and DHA in a fish oil/omega-3 supplement.
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.
Several small studies have shown that combination therapy with fish oil and HMG CoA reductase inhibitors is safe.56–61 The largest trial to date, the JELIS trial,32 was an open label trial of 18,645 Japanese adults with hypercholesterolemia who were randomized to a standard statin regimen or a fish oil formulation containing 1.8 g of EPA added to a statin medication. The cohort was made up mostly of postmenopausal, nonobese women with a 15% to 20% incidence of diabetes, tobacco use, or CAD. The primary outcome of any major cardiovascular event, at a mean of 4.6 years, was moderately reduced by a relative risk reduction of 26%. Both unstable angina and nonfatal MI were reduced, but no change was seen in sudden death. Overall, the findings were remarkable because at baseline approximately 90% of Japanese consumed at least 900 mg of EPA and DHA per day.62 The rates of cancer, joint pain, lumbar pain, or muscle pain were similar in the 2 groups. There was a similar rate of increase in measures of creatine phosphokinase, but more patients had an increase in aspartate aminotransferase levels (0.6% vs. 0.4%) in the fish oil group. The rate of bleeding was 1.1% in the fish oil combination group versus 0.6% in the HMG–CoA reductase inhibitor group.
In your final paragraph, you suggest that a ratio of 2:1 EPA/DHA maybe best for reducing inflammation. Are you suggesting using two separate products to obtain that ratio? I can't see how it is achieveable through standard omega-3 products. Good fish oil brands are typically 60% or higher EPA, but never reach a 2:1 ratio in my product searches. According to case studies (link below), 1 gram of EPA per day (60% or more of the total omega-3 content) is sufficient and the highest efficacy.
In many cases, people are recommended to consume fish oil because it is an easy way to get additional omega-3 fatty acids into their diet. Omega-3 fats can be used to reduce swelling or to prevent blood clots which could cause major cardiovascular damage. There are many other conditions which can be decreased or improved with the use of fish oil. In most cases fish oil is used to help reduce high triglycerides which can cause serious conditions like diabetes or heart disease.

Fish oils seem to decrease blood pressure. Taking fish oils along with medications for high blood pressure might cause your blood pressure to go too low.Some medications for high blood pressure include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), Amlodipine (Norvasc), hydrochlorothiazide (HydroDiuril), furosemide (Lasix), and many others.
I've done a lot of shopping and comparing of fish oil softgels and have reached the conclusion that these are these best you can buy. Prior to seeing these in my chiropractor's office I scanned the labels and specs on many brands at Mothers, Vitamin Shoppe, Sprouts and Amazon vendors. These have 430 mg of EPA and 290 mg of DHA per softgel, with a recommended dose of two.. If you compare as well, you will find most other brands, including those sold as premium products at health food stores at premium prices don't have the same potency.Especially among Krill Oil products. My chiropractor shared a clinical study that showed taking fish oil containing levels of EPA and DHA consistent with these supplements caused participants to say it had the same favorable affect as taking ibuprofen. I make no claims. I am not a doctor, am not associated ... full review

After a large number of lab studies found that omega-3 fatty acids may be effective in slowing or reversing the growth of hormonal cancers, namely prostate and breast cancer cells, animal and human epidemiological studies have been conducted to see whether this effect occurred in real-life scenarios. The evidence is somewhat conflicting in some reports, but there is some evidence to suggest breast and prostate cancers may be potentially slowed (or the risk reduced) in people who eat a lot of oily fish and possibly those who supplement with omega-3. (66, 67, 68)
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]
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.
Your body also needs omega-6s, another type of fatty acid, to function properly and prevent disease. Unfortunately, these are found in much more abundance than omega-3s in the standard American diet, although your body craves a 1:1 ratio to keep inflammation low. Most modern diets contain a ratio closer to 20:1 or 30:1 omega-6 to omega-3 fatty acids.
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.
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)
Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.
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.
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).
During pregnancy and breastfeeding, eating 8 to 12 ounces per week of fish and other seafood may improve your baby’s health. However, it is important to choose fish that are higher in EPA and DHA and lower in mercury. Examples are salmon, herring, sardines, and trout. It is not clear whether taking dietary supplements containing EPA and DHA during pregnancy or breastfeeding affects a baby’s health or development. However, some studies show that taking these supplements may slightly increase a baby’s weight at birth and the length of time the baby is in the womb, both of which may be beneficial. Breast milk contains DHA. Most commercial infant formulas also contain DHA.
Fish oils might slow blood clotting. Taking fish oils along with medications that also slow clotting might increase the chances of bruising and bleeding.Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.
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