This constant sweeping motion of DHA also causes the breakup of lipid rafts in membranes (8). Disruption of these islands of relatively solid lipids makes it more difficult for cancer cells to continue to survive and more difficult for inflammatory cytokines to initiate the signaling responses to turn on inflammatory genes (9). In addition, the greater spatial characteristics of DHA increase the size of LDL particles to a greater extent compared to EPA. As a result, DHA helps reduce the entry of these enlarged LDL particles into the muscle cells that line the artery thus reducing the likelihood of developing atherosclerotic lesions (10). Thus the increased spatial territory swept out by DHA is good news for making certain areas of membranes more fluid or lipoprotein particles larger, even though it reduces the benefits of DHA in competing with AA for key enzymes important in the development of cellular inflammation.
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.
In later life, cognitive function and brain deterioration may become a concern. Once again, maintaining high levels of EPA has been shown to lower the risk of developing and worsening cognitive decline and dementia. If, however, you know someone who already has a diagnosis of dementia or Alzheimer’s, their brain has already been damaged and needs structural support. At this point, DHA becomes important again and taking a high-EPA product that contains 250mg of DHA also is important to prevent further loss of brain tissue.
Heavy metal poisoning by the body's accumulation of traces of heavy metals, in particular mercury, lead, nickel, arsenic, and cadmium, is a possible risk from consuming fish oil supplements.[medical citation needed] Also, other contaminants (PCBs, furans, dioxins, and PBDEs) might be found, especially in less-refined fish oil supplements.[citation needed] However, heavy metal toxicity from consuming fish oil supplements is highly unlikely, because heavy metals selectively bind with protein in the fish flesh rather than accumulate in the oil. An independent test in 2005 of 44 fish oils on the US market found all of the products passed safety standards for potential contaminants.[107][unreliable source?]
The GISSI-Heart Failure trial was the first blinded, randomized trial to assess the efficacy of fish oil supplements in patients with heart failure.51 The trial enrolled 7046 subjects with heart failure; 60% with New York Heart Association class II symptoms and 40% with a history of MI. The majority of patients were on a standard heart failure regimen, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, and spironolactone, but only 22% were on a statin. At an average of 3.9 years, the coprimary end points of death and death or hospital admission for cardiovascular reasons were reduced by approximately 9% with fish oil supplementation. Sudden cardiac death, a secondary end-point, showed a statistically nonsignificant relative risk reduction of 7% with fish oil. There was also a reduction in 2 other arrhythmia-related secondary end-points: first hospitalization for ventricular arrhythmia and presumed arrhythmic death.
Fortier, M., Tremblay-Mercier, J., Plourde, M., Chouinard-Watkins, R., Vandal, M., Pifferi, F., Freemantle, E., and Cunnane, S. C. Higher plasma n-3 fatty acid status in the moderately healthy elderly in southern Quebec: higher fish intake or aging-related change in n-3 fatty acid metabolism? Prostaglandins Leukot.Essent.Fatty Acids 2010;82(4-6):277-280. View abstract.
Fish oil is useful in the treatment of arthritis, rheumatism, Raynaud’s symptoms and similar conditions. Using the fish oil can help in reducing the need for large dosages of NSAIDs (non-steroidal anti-inflammatory drugs). The Royal Adelaide Hospital and the University of Newcastle, located in Australia, have reported that fish oil has shown positive effects in the treatment of arthritis. In cases of osteoarthritis, fish oil can be helpful in reducing the impact of enzymes that destroy cartilage.
Heart rate variability, a possible surrogate outcome for the risk of sudden death, was assessed in a randomized trial of myocardial infarction (MI) survivors with an ejection fraction of 40%. In the 49 patients that were randomized to either fish oil or olive oil, Holter monitor recordings showed an increase in heart rate variability in the fish oil group.31 In a larger cohort assessed in the Japan EPA Lipid Intervention Study (JELIS),32 however, no difference in heart rate variability could be attributed to fish oil.
Age-related macular degeneration (AMD) is an eye disease that can cause vision loss in older people. Two major National Institutes of Health (NIH)-sponsored studies, called Age-Related Eye Disease Study (AREDS) and Age-Related Eye Disease Study 2 (AREDS2), showed that dietary supplements containing specific combinations of vitamins, antioxidants, and zinc helped slow the progression of AMD in people who were at high risk of developing the advanced stage of this disease. AREDS2, which had more than 4,000 participants and was completed in 2013, also tested EPA and DHA. The results showed that adding these omega-3s to the supplement formulation didn’t provide any additional benefits. Other, smaller studies of omega-3 supplements also haven’t shown them to have a beneficial effect on the progression of AMD. 
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.

Finally, in order for AA to be converted into inflammatory products it must be released from phospholipids (part of the cell membrane) using the enzyme phospholipase A2 and then converted by the enzyme cyclooxygenase. EPA utilises both of these enzymes, so if EPA levels are increased in the diet, it attracts enzyme away from AA to EPA – again giving rise to anti-inflammatory products instead of inflammatory ones.

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]
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
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.
AD is a devastating disease for which there are limited treatment options and no cure. Memory loss is an early indicator of the disease, which is progressive, and leads to the inability of the patient to care for him- or herself and eventually to death (47). Currently, the number of individuals with AD is estimated to be 26.6 million and is expected to increase to 106.2 million by 2050 (48). There have been many studies conducted regarding the use of omega-3 fatty acid supplementation and AD (Table 2). DHA is present in large amounts in neuron membrane phospholipids, where it is involved in proper function of the nervous system, which is why it is thought to play a role in AD (49). A case-control study consisting of 148 patients with cognitive impairment [Mini-Mental State Examination (MMSE) score <24] and 45 control patients (MMSE score ≥24) showed that serum cholesteryl ester-EPA and -DHA levels were significantly lower (P < 0.05 and P < 0.001, respectively) in all MMSE score quartiles of patients with AD compared with control values (49). Another study found that a diet characterized by higher intakes of foods high in omega-3 fatty acids (salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, dark and green leafy vegetables), and a lower intake of foods low in omega-3 fatty acids (high-fat dairy products, red meat, organ meat, butter) was strongly associated with a lower AD risk (50). Image analysis of brain sections of an aged AD mouse model showed that overall plaque burden was significantly reduced by 40.3% in mice with a diet enriched with DHA (P < 0.05) compared with placebo. The largest reductions (40–50%) were seen in brain regions that are thought to be involved with AD, the hippocampus and parietal cortex (51). A central event in AD is thought to be the activation of multiple inflammatory cells in the brain. Release of IL-1B, IL-6, and TNF α from microglia cells may lead to dysfunction of the neurons in the brain (52). In 1 study, AD patients treated with EPA+DHA supplementation increased their plasma concentrations of EPA and DHA, which were associated with reduced release of inflammatory factors IL-1B, IL-6, and granulocyte colony–stimulating factor from peripheral blood mononuclear cells (53).
36. Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R, Franzosi MG, Geraci E, Levantesi G, Maggioni AP, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation. 2002;105:1897–903. [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.
Birch, E. E., Carlson, S. E., Hoffman, D. R., Fitzgerald-Gustafson, K. M., Fu, V. L., Drover, J. R., Castaneda, Y. S., Minns, L., Wheaton, D. K., Mundy, D., Marunycz, J., and Diersen-Schade, D. A. The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Am J Clin Nutr 2010;91(4):848-859. View abstract.
Several other analyses of the evidence have been done in the last few years (2012 or later), and like the 2018 analysis and the AHRQ report, most found little or no evidence for a protective effect of omega-3 supplements against heart disease. However, some earlier analyses suggested that omega-3s could be helpful. The difference between the newer conclusions and the older ones may reflect two changes over time: 
Nielsen, A. A., Jorgensen, L. G., Nielsen, J. N., Eivindson, M., Gronbaek, H., Vind, I., Hougaard, D. M., Skogstrand, K., Jensen, S., Munkholm, P., Brandslund, I., and Hey, H. Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acids. Aliment.Pharmacol.Ther. 2005;22(11-12):1121-1128. View abstract.
Your retina contains quite a bit of DHA, making it necessary for that fatty acid to function. (90) The National Eye Institute, part of the National Institutes of Health, concludes that there is “consistent evidence” suggesting long-chain polyunsaturated fatty acids DHA and EPA are necessary for retinal health and may help protect the eyes from disease. (91)
At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.
Maclean, C. H., Mojica, W. A., Morton, S. C., Pencharz, J., Hasenfeld, Garland R., Tu, W., Newberry, S. J., Jungvig, L. K., Grossman, J., Khanna, P., Rhodes, S., and Shekelle, P. 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. Evid.Rep.Technol.Assess.(Summ.) 2004;(89):1-4. View abstract.
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)
Recent studies have shown that the consumption of fish oil (or, more specifically, the omega-3 fatty acids found in fish oil) can improve fertility in both men and women. DHA, which is a byproduct of omega-3 fatty acids, plays a key role in the mobility of sperm and health of sperm in men. Low blood levels of DHA have been linked to decreased fertility. Animal studies have found that the DHA in fish is vital to changing dysfunctional round-headed sperm into strong swimmers with cone-shaped heads packed with egg-opening proteins. (29)
Currently, there isn’t a set standard recommendation for how many omega-3s we need each day, but suggestions range from a fish oil dosage of 500 to 1,000 milligrams daily depending on whom you ask. How easy is it to get these recommended amounts? To give you an idea, there are more than 500 milligrams of total omega-3s in one can of tuna fish and one small serving of wild-caught salmon.
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]

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.
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.

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.

Studies don’t seem to mention blood content of omega 6, or saturated fats–the overall balnce of triglycerides, so they seem to have been done in a “vacuum”. At least, the data is so presented. Also, high protein may be an issue not being tested, but hovering in the background of the participants’ diets. Many “miracle cures”, and I wish it wasnt so, are being not only “debunked”, but “proven” outright dangerous.

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)
EPA is the precursor to DHA in the body and can be converted to DHA with the enzyme delta-6 desaturase, but this process is inefficient in many people (much like the inefficiency of short-chain omega-3s to long-chain). For those individuals taking pure EPA products as well as those taking our EPA-rich products, we still recommend eating oily fish at least once each week to provide a natural source of DHA. Fish provides a unique nutritional package, supplying the diet with important amino acids (the building blocks of proteins) and antioxidants, including vitamins and minerals needed to process fats, so eating fish will also support the natural enzyme-dependent EPA to DHA conversion.
For preventing and reversing the progression of hardening of the arteries after angioplasty: 6 grams of fish oil daily starting one month before angioplasty and continuing for one months after, followed by 3 grams daily for 6 months thereafter has been used. Also, 15 grams of fish oil has been taken daily for 3 weeks before angioplasty and for 6 months thereafter.
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