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.
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.

Although there was significant heterogeneity among the included studies (Cochran Q, 178.820; df, 18; I2, 89.934%; P < .001), the sensitivity test suggested that the main significant results of the meta-analysis would not change after removal of any of the included studies. However, through direct inspection of the forest plot, we detected the potential influence of some outliers, such as the studies by Sohrabi et al56 and Yehuda et al.61 These 2 studies evaluated anxiety symptoms with a visual analog scale of anxiety and test anxiety severity, which are seldom used in psychiatric research and lack a definite report to prove their equivalent sensitivity and specificity to some other frequently used anxiety rating scales, such as depression, anxiety, and stress scales or the Hamilton anxiety rating scale. Therefore, these studies might have affected the interpretation of the current meta-analysis.

As you likely know (and as I’ve been discussing for years), omega-3 fatty acids have anti-inflammatory properties. They have been studied for the treatment and prevention of many diseases, several of which are related to inflammation, including heart disease, stroke, cancer, and Alzheimer’s disease. They have also been shown to be extraordinarily helpful in preventing and treating other brain conditions such as depression and other psychiatric disorders, attention deficit/hyperactivity disorder (ADHD), and concussions.
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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]
Omega-3 fats may also impact the development of arthritis. As far back as 1959, studies were published about the effectiveness of cod liver oil on arthritic patients. In the 1959 study, 93 percent of participants “showed major clinical improvement.” (73) While there is no evidence that high omega-3 levels can prevent the development of arthritis, it seems clear that they can reduce inflammation that causes the typical bone and joint pain experienced in the disease. (74)

Higher visual acuity after DHA supplementation is a consistent finding in infants born preterm. For infants born at term, the results are less consistent and are better explained by differences in sensitivity of the visual acuity test (electrophysiologic tests being more sensitive than subjective tests) or by differences in the amount of DHA included in the experimental formula.
Hanwell, H. E., Kay, C. D., Lampe, J. W., Holub, B. J., and Duncan, A. M. Acute fish oil and soy isoflavone supplementation increase postprandial serum (n-3) polyunsaturated fatty acids and isoflavones but do not affect triacylglycerols or biomarkers of oxidative stress in overweight and obese hypertriglyceridemic men. J Nutr 2009;139(6):1128-1134. View abstract.
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.
Jump up ^ Burch, Ernest S. (2006). Social Life in Northwest Alaska: The Structure of Iñupiaq Eskimo Nations. University of Alaska Press. p. 278. ISBN 9781889963921. Retrieved 2014-10-23. Oil was also used externally as an ointment to heal cold sores, cuts, insect bites, frostbite, rashes - in short, skin problems of all kinds. Duck or goose body-cavity fat was apparently as useful as seal or fish oil in dealing with skin problems.

Research conducted at the Louisiana State University has shown that fatty acids are effective in treating Alzheimer’s disease. Since fish oil is one of the best sources of essential fatty acids, including EPA and DHA, it helps in the treatment of Alzheimer’s disease. More research conducted at the University of California in Los Angeles (UCLA) validates the usefulness of fish oil as a possible remedy for the disease. The Alzheimer’s Association recommends fish containing a higher content of omega-3 fatty acids to patients since it acts as a defense against Alzheimer’s disease and dementia.

^ Jump up to: a b Casula M, Soranna D, Catapano AL, Corrao G (August 2013). "Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: A meta-analysis of randomized, placebo controlled trials [corrected]". Atherosclerosis. Supplements. 14 (2): 243–51. doi:10.1016/S1567-5688(13)70005-9. PMID 23958480.

Yamagishi, K., Iso, H., Date, C., Fukui, M., Wakai, K., Kikuchi, S., Inaba, Y., Tanabe, N., and Tamakoshi, A. Fish, omega-3 polyunsaturated fatty acids, and mortality from cardiovascular diseases in a nationwide community-based cohort of Japanese men and women the JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study. J.Am.Coll.Cardiol. 9-16-2008;52(12):988-996. View abstract.

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).

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.
CHAMPAIGN, Ill. — Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its euphoric effects, but it also has anti-inflammatory benefits. A new study in animal tissue reveals the cascade of chemical reactions that convert omega-3 fatty acids into cannabinoids that have anti-inflammatory benefits – but without the psychotropic high.
(How much omega-3 is necessary to increase one’s omega-3 index?  Studies show it can take between 1800 – 2000 mg of EPA/DHA daily to move a person’s index by 4 – 5 percentage points (12). Importantly, this is a much larger dose than you’d get swallowing one or two regular fish oil capsules and could well explain why many traditional omega-3 products fail to deliver results.)

A lot of the benefit of fish oil seems to come from the omega-3 fatty acids that it contains. Interestingly, the body does not produce its own omega-3 fatty acids. Nor can the body make omega-3 fatty acids from omega-6 fatty acids, which are common in the Western diet. A lot of research has been done on EPA and DHA, two types of omega-3 acids that are often included in fish oil supplements.