Since EPA and DHA are both essential for health and appear together in nature, many studies have attempted to treat clinical conditions with combined EPA and DHA oils, but the outcomes have been varied, contradictory and disappointing. Consequently, researchers have started to investigate the individual actions of EPA and DHA in isolation, in numerous health conditions where an omega-3 deficiency is related to symptoms or known to play a causative role. The emerging evidence shows marked differences between how these two fatty acids affect us – not just at the cellular level but also the body as a whole.

ALA is an essential fatty acid, meaning that your body can’t make it, so you must get it from the foods and beverages you consume. Your body can convert some ALA into EPA and then to DHA, but only in very small amounts. Therefore, getting EPA and DHA from foods (and dietary supplements if you take them) is the only practical way to increase levels of these omega-3 fatty acids in your body.
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.
ALA is an essential fatty acid, which means that you need it but you must get this fat from your diet because your body is unable to produce it. In general, omega 3 fats are a crucial component of all cell membranes, including the eye (retina) and brain as well as aiding in the process of energy production to support functions involving the heart, lungs, immune system, and hormones (endocrine system), work properly.1
The number, location, and orientation of the double bonds determine the health effects of fatty acids on the body. One aspect of this is their effect on triglycerides and LDL and HDL types of cholesterol, which in turn affect how much cholesterol gets deposited on the inside of blood vessels. There are also subtypes of LDL and HDL which are also likely important to their health effects.

The three types of omega−3 fatty acids involved in human physiology are α-linolenic acid (ALA), found in plant oils, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both commonly found in marine oils.[2] Marine algae and phytoplankton are primary sources of omega−3 fatty acids. Common sources of plant oils containing ALA include walnut, edible seeds, clary sage seed oil, algal oil, flaxseed oil, Sacha Inchi oil, Echium oil, and hemp oil, while sources of animal omega−3 fatty acids EPA and DHA include fish, fish oils, eggs from chickens fed EPA and DHA, squid oils, and krill oil. Dietary supplementation with omega−3 fatty acids does not appear to affect the risk of death, cancer or heart disease.[4][5] Furthermore, fish oil supplement studies have failed to support claims of preventing heart attacks or strokes or any vascular disease outcomes.[6][7]
42. Cawood AL, Ding R, Napper FL, Young RH, Williams JA, Ward MJ, Gudmundsen O, Vige R, Payne SP, Ye S, et al. Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. Atherosclerosis. 2010;212:252–9. [PubMed]
Evidence linking fish oil and cancer has been all over the map. Some research suggests diets high in fatty fish or fish oil supplements might reduce the risk of certain cancers, including prostate cancer. Other research shows just the opposite, a  link between eating a lot of oily fish or taking potent fish oil supplements and a 43% increased risk for prostate cancer overall, and a 71% increased risk for aggressive prostate cancer.
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.
Pay attention to the quality of fish oil when purchasing it. It is obtained from almost all fishes – fresh water, farm, ocean, deep sea and shallow sea fish. All these fishes can be contaminated with toxic compounds such as mercury, arsenic, lead, forms of calcium, furans, dioxins, PCBs, and methylmercury, and can negatively affect the human body. Therefore, the fish oil used must be pure. Many companies sell ultra refined or distilled fish oil, but you should always check if the standards have been followed and research on the company or the product before adding it to your diet.

The evidence linking the consumption of marine omega−3 fats to a lower risk of cancer is poor.[8][13] With the possible exception of breast cancer,[8][14][15] there is insufficient evidence that supplementation with omega−3 fatty acids has an effect on different cancers.[5][16] The effect of consumption on prostate cancer is not conclusive.[8][15] There is a decreased risk with higher blood levels of DPA, but an increased risk of more aggressive prostate cancer was shown with higher blood levels of combined EPA and DHA.[17] In people with advanced cancer and cachexia, omega−3 fatty acids supplements may be of benefit, improving appetite, weight, and quality of life.[18]
The ultimate goal of using omega-3 fatty acids is the reduction of cellular inflammation. Since eicosanoids derived from arachidonic acid (AA), an omega-6 fatty acid, are the primary mediators of cellular inflammation, EPA becomes the most important of the omega-3 fatty acids to reduce cellular inflammation for a number of reasons. First, EPA is an inhibitor of the enzyme delta-5-desaturase (D5D) that produces AA (1). The more EPA you have in the diet, the less AA you produce. This essentially chokes off the supply of AA necessary for the production of pro-inflammatory eicosanoids (prostaglandins, thromboxanes, leukotrienes, etc.). DHA is not an inhibitor of this enzyme because it can’t fit into the active catalytic site of the enzyme due to its larger spatial size. As an additional insurance policy, EPA also competes with AA for the enzyme phospholipase A2 necessary to release AA from the membrane phospholipids (where it is stored). Inhibition of this enzyme is the mechanism of action used by corticosteroids. If you have adequate levels of EPA to compete with AA (i.e. a low AA/EPA ratio), you can realize many of the benefits of corticosteroids but without their side effects. That’s because if you don’t release AA from the cell membrane then you can’t make inflammatory eicosanoids. Because of its increased spatial dimensions, DHA is not a good competitor of phospholipase A2 relative to EPA. On the other hand, EPA and AA are very similar spatially so they are in constant competition for the phospholipase A2 enzyme just as both fatty acids are in constant competition for the delta-5 desaturase enzyme. This is why measuring the AA/EPA ratio is such a powerful predictor of the state of cellular inflammation in your body.
Cancer. Research on the effects of fish oil in preventing cancer has produced conflicting results. Some population research suggests that eating fish or having higher blood levels of omega-3 fatty acids from fish oil is linked to a lower risk of different cancers, including oral cancer, pharyngeal cancer, esophageal cancer, colon cancer, rectal cancer, breast cancer, ovarian cancer, and prostate cancer. But other research suggests that eating fish does not reduce the risk of cancer.

Muñoz MA, Liu W, Delaney JA, Brown E, Mugavero MJ, Mathews WC, Napravnik S, Willig JH, Eron JJ, Hunt PW, Kahn JO, Saag MS, Kitahata MM, Crane HM. Comparative effectiveness of fish oil versus fenofibrate, gemfibrozil, and atorvastatin on lowering triglyceride levels among HIV-infected patients in routine clinical care. J Acquir Immune Defic Syndr 2013;64(3):254-60. View abstract.
These conversions occur competitively with omega−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. They both utilize the same desaturase and elongase proteins in order to synthesize inflammatory regulatory proteins.[50] The products of both pathways are vital for growth making a balanced diet of omega−3 and omega−6 important to an individual's health.[77] A balanced intake ratio of 1:1 was believed to be ideal in order for proteins to be able to synthesize both pathways sufficiently, but this has been controversial as of recent research.[78]

Nonetheless, large population studies with solid data both on the participants’ diets and causes of disease and death bolstered the beliefs that eating fish often was a heart-healthy practice linked to reduced rates of cardiovascular disease. For example, a comprehensive analysis conducted by Dr. Dariush Mozaffarian and Eric Rimm of the Harvard T.H. Chan School of Public Health found that eating two servings of fatty fish a week — equal to about two grams of omega-3 fatty acids — lowered the risk of death from heart disease by more than a third and total deaths by 17 percent.
Fish oil can be obtained from eating fish or by taking supplements. Fish that are especially rich in the beneficial oils known as omega-3 fatty acids include mackerel, herring, tuna, salmon, cod liver, whale blubber, and seal blubber. Two of the most important omega-3 fatty acids contained in fish oil are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Make sure to see separate listings on EPA and DHA, as well as Cod Liver Oil, and Shark Liver Oil.
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