If, however, we want to target the actions and benefits of either fat for more intensive support or clinical use, we need to alter the natural 1.5:1 EPA:DHA ratio found in most omega-3 sources such as fish oil – which is when concentrated supplements are especially useful. Certain forms of omega-3 called ethyl-ester and re-esterified triglyceride give nature a helping hand – allowing us to achieve targeted ratios of specific fatty acids at high concentration and physiologically active doses.
Omega-3s have been studied for other conditions, with either inconclusive or negative results. These conditions include allergies, atopic eczema (an allergic skin condition), cystic fibrosis, diabetes, inflammatory bowel diseases (Crohn’s disease or ulcerative colitis), intermittent claudication (a circulatory problem), nonalcoholic fatty liver disease, and osteoporosis. 
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.
We’ve written about the dose necessary to achieve measurable benefits before. However, a person’s actual omega-3 intake can be tricky to estimate. Even if you eat at least two servings of fatty fish per week, as the American Heart Association recommends (10), your fish might contain more or less omega-3s depending on the fish species, the time of year, and how you cook it. Even taking fish oil supplements isn’t always straightforward, as dose can be impacted by numerous bioavailability factors, as well as genetics, age, gender, medication-use and lifestyle.
The European Journal of Neuroscience published a study in 2013 showing that fish oil reversed all anxiety-like and depression-like behavior changes induced in rats. This is an interesting study because it stresses the importance of supplementing with fish oil at “critical periods of brain development.” (10) This is exactly why I recommend giving fish oil to our kids from early on to help them so they won’t develop anxiety or depression later in life.
However, in both observational studies and controlled clinical trials, eating fish was shown to foster optimal development of a baby’s brain and nervous system, prompting advice that pregnant women and nursing mothers eat more fish rich in omega-3s while avoiding species that may contain mercury or other contaminants like PCBs sometimes found in freshwater fish.

In my opinion, the key benefit of DHA lies in its unique spatial characteristics. As mentioned earlier, the extra double bond (six in DHA vs. five in EPA) and increased carbon length (22 carbons in DHA vs. 20 in EPA) means that DHA takes up takes up a lot more space than does EPA in the membrane. Although this increase in spatial volume makes DHA a poor substrate for phospholipase A2 as well as the COX and LOX enzymes, it does a great job of making membranes (especially those in the brain) a lot more fluid as the DHA sweeps out a much greater volume in the membrane than does EPA. This increase in membrane fluidity is critical for synaptic vesicles and the retina of the eye as it allows receptors to rotate more effectively thus increasing the transmission of signals from the surface of the membrane to the interior of the nerve cells. This is why DHA is a critical component of these highly fluid portions of the nerves (7). On the other hand, the myelin membrane is essentially an insulator so that relatively little DHA is found in that part of the membrane.


For several years now, the fish oil and Alzheimer’s disease connection has been studied with consistent results. The essential fatty acids vital for brain function that are found in fish oil can not only slow cognitive decline, but can help prevent brain atrophy in older adults. A study published in the FASEB Journal looked at the health effects of four- to 17-month dietary supplementation with omega-3 fatty acids and antioxidants. The findings once again confirm the potential for fish oil to be used as a weapon to fend off the onset of cognitive decline and Alzheimer’s disease. (8)
Sala-Vila A, Díaz-López A, Valls-Pedret C, et al.; Prevención con Dieta Mediterránea (PREDIMED) Investigators. Dietary marine ?-3 fatty acids and incident sight-threatening retinopathy in middle-aged and older individuals with type 2 diabetes: Prospective investigation from the PREDIMED trial. JAMA Ophthalmol. 2016;134(10):1142-1149. View abstract.
Several large studies have linked higher blood levels of long-chain omega-3s with higher risks of prostate cancer. However, other research has shown that men who frequently eat seafood have lower prostate cancer death rates and that dietary intakes of long-chain omega-3s aren’t associated with prostate cancer risk. The reason for these apparently conflicting findings is unclear. 
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.
For those who do not eat seafood, another way exists for you to get a healthy dose of EPA and DHA each day. Fish oil supplements, which are rich in EPA and DHA, can be made from a variety of fish, with the most common ones being halibut, tuna, salmon, cod liver, mackerel and herring. On average, one 3.5 ounce serving of fatty fish contains about 1 gram of omega-3s, which can be obtained through fish oil supplements, according to MedlinePlus.
The chemical structure of eicosapentaenoic acid and docosahexaenoic acid. Eicosapentaenoic acid consists of 20 carbons (C20) with 5 double bonds, and the last unsaturated carbon is located third from the methyl end (n-3). Do-cosahexaenoic acid consists of 22 carbons (C22) with 6 double bonds, and also with the3 last unsaturated carbon located third from the methyl end (n-3). Adapted with permission from Frishman et al, eds. Cardiovascular Pharmacotherapeutics. New York, NY: McGraw Hill; 2003.3

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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
Fish oil seems to be a subject of controversy. Some people swear by it, and there are thousands of clinical trials out now trying to study what the latest and greatest thing about the supplement is. The Natural Standard does a really good job collecting and gathering data for those who are interested in delving through what fish oil may or may not be doing to us. Definitive answers, however, may take a little while to get.
A number of trials have found that omega-3 PUFAs might reduce anxiety under serious stressful situations. Case-controlled studies have shown low peripheral omega-3 PUFA levels in patients with anxiety disorders.27-31 A cohort study found that high serum EPA levels were associated with protection against posttraumatic stress disorder.32 In studies of therapeutic interventions, while a randomized clinical trial of adjunctive EPA treatment in patients with obsessive-compulsive disorder revealed that EPA augmentation had no beneficial effect on symptoms of anxiety, depression, or obsessive-compulsiveness,33 a randomized clinical trial involving participants with substance abuse showed that EPA and DHA administration was accompanied by significant decreases in anger and anxiety scores compared with placebo.34 In addition, a randomized clinical trial found that omega-3 PUFAs had additional effects on decreasing depressive and anxiety symptoms in patients with acute myocardial infarction,35 and a randomized clinical trial demonstrated that omega-3 PUFAs could reduce inflammation and anxiety among healthy young adults facing a stressful major examination.36 Despite the largely positive findings of these trials, the clinical application of the findings is unfortunately limited by their small sample sizes.
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.

Whilst EPA and DHA are both considered to be important regulators of immunity, platelet aggregation and inflammation, their health-influencing by-products arise from very different pathways and their effects in the body differ. DHA is the most abundant omega-3 fatty acid in cell membranes, present in all organs and most abundant in the brain and retina, playing an important structural role. EPA is present structurally only in minute quantities, always being utilised and under constant demand to be replaced. Whilst DHA provides mainly a structural role, it is becoming evident that EPA may be the dominant functional fatty acid out of the two in many areas of health and especially in inflammatory conditions.
For dry eye: Fish oil supplements providing EPA 360-1680 mg and DHA 240-560 mg have been used for 4-12 weeks. Some people used the specific product (PRN Dry Eye Omega Benefits softgels). A specific combination product containing EPA 450 mg, DHA 300 mg, and flaxseed oil 1000 mg (TheraTears Nutrition, Advanced Nutrition Research; Caruso’s Natural Health UltraMAX fish oil, Sydney, New South Wales, Australia) has been used once daily for 90 days.
A March 2010 lawsuit filed by a California environmental group claimed that eight brands of fish oil supplements contained excessive levels of PCB's, including CVS/pharmacy, Nature Made, Rite Aid, GNC, Solgar, Twinlab, Now Health, Omega Protein and Pharmavite. The majority of these products were either cod liver or shark liver oils. Those participating in the lawsuit claim that because the liver is the major filtering and detoxifying organ, PCB content may be higher in liver-based oils than in fish oil produced from the processing of whole fish.[63][64]
The GISSI-Prevenzione trial40 showed similar findings. In this open-label trial, 11,324 post-MI patients were followed for 3.5 years after randomization to either 1 g/d of omega-3 FA, vitamin E, both, or none. In the 2836 patients assigned to only omega-3 FA, the primary end point of death, nonfatal MI or stroke, was reduced by 10%. This decreased risk occurred despite a minimal triglyceride-lowering effect because of the relatively low dose of omega-3 FA. Of note, the GISSI-Prevenzione trial was done prior to the pervasive use of lipid-lowering agents. Only about 40% of patients were on any form of lipid-lowering therapy.
Fish oil supplements in our study averaged 473.3mg EPA + 243.1mg DHA in a single serving. These average values were stretched by outliers on both extremes of the spectrum. Nature Made Cod Liver Oil (50mg EPA/serving) and Schiff MegaRed Krill Oil (29mg DHA/serving) recorded category lows for the two omega-3 fatty acids. Ocean Blue Professional Omega-3 (1260mg EPA/serving) and Dr. Tobias Optimum Omega-3 Fish Oil (600mg DHA/serving), on the other hand, recorded category highs for EPA and DHA content.
The 'essential' fatty acids were given their name when researchers found that they are essential to normal growth in young children and animals. The omega−3 fatty acid DHA, also known as docosahexaenoic acid, is found in high abundance in the human brain.[70] It is produced by a desaturation process, but humans lack the desaturase enzyme, which acts to insert double bonds at the ω6 and ω3 position.[70] Therefore, the ω6 and ω3 polyunsaturated fatty acids cannot be synthesized and are appropriately called essential fatty acids.[70]
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.

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.
^ Jump up to: a b Jensen, Craig L.; Voigt, Robert G.; Llorente, Antolin M.; Peters, Sarika U.; Prager, Thomas C.; Zou, Yali L.; Rozelle, Judith C.; Turcich, Marie R.; Fraley, J. Kennard; Anderson, Robert E.; Heird, William C. (2010). "Effects of Early Maternal Docosahexaenoic Acid Intake on Neuropsychological Status and Visual Acuity at Five Years of Age of Breast-Fed Term Infants". The Journal of Pediatrics. 157 (6): 900–05. doi:10.1016/j.jpeds.2010.06.006. PMID 20655543.
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
Ozaydin, M., Erdogan, D., Tayyar, S., Uysal, B. A., Dogan, A., Icli, A., Ozkan, E., Varol, E., Turker, Y., and Arslan, A. N-3 polyunsaturated fatty acids administration does not reduce the recurrence rates of atrial fibrillation and inflammation after electrical cardioversion: a prospective randomized study. Anadolu.Kardiyol.Derg. 2011;11(4):305-309. View abstract.
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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