The most widely available dietary source of EPA and DHA is cold-water oily fish, such as salmon, herring, mackerel, anchovies, and sardines. Oils from these fish have a profile of around seven times as much omega-3 oils as omega-6 oils. Other oily fish, such as tuna, also contain omega-3 in somewhat lesser amounts. Although fish is a dietary source of omega-3 oils, fish do not synthesize them; they obtain them from the algae (microalgae in particular) or plankton in their diets.[22]
If you have a bleeding disorder, bruise easily or take blood-thinning medications, you should use fish oil supplements with extra caution since large doses of omega-3 fatty acids can increase bleeding risk. This bleeding risk also applies to people with no history of bleeding disorders or current medication usage. If you have type 2 diabetes, you should only use fish oil supplements under your doctor’s supervision. Individuals with type 2 diabetes can experience increases in fasting blood sugar levels while taking fish oil supplements.
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.
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.
Jump up ^ Kwak SM, Myung SK, Lee YJ, Seo HG (May 2012). "Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials". Archives of Internal Medicine. 172 (9): 686–94. doi:10.1001/archinternmed.2012.262. PMID 22493407.
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 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
An animal study involving the omega-3 ETA discovered that subjects experienced a drop in overall inflammation similar to that caused by NSAIDs (non-steroidal anti-inflammatory drugs), but without the dangerous gastrointestinal side effects. The study authors also pointed out that eicosapentaenoic acid seems to be even more potent than the conventional omega-3s found in fish oil supplements (EPA/DHA). (56)
Fish Oil capsules contain omega-3 polyunsaturated fatty acids. Omega-3 polyunsaturated fatty acids are found in oils from certain types of fish, vegetables, and other plant sources. These fatty acids are not made by the body and must be consumed in the diet. Omega-3 polyunsaturated fatty acids work by lowering the body's production of triglycerides. High levels of triglycerides can lead to coronary artery disease, heart disease, and stroke.
The U.S. Food and Drug Administration recommends consuming no more than 3 g/day of EPA and DHA combined, including up to 2 g/day from dietary supplements. Higher doses are sometimes used to lower triglycerides, but anyone taking omega-3s for this purpose should be under the care of a healthcare provider because these doses could cause bleeding problems and possibly affect immune function. Any side effects from taking omega-3 supplements in smaller amounts are usually mild. They include an unpleasant taste in the mouth, bad breath, heartburn, nausea, stomach discomfort, diarrhea, headache, and smelly sweat.
^ 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.
Back in 2013, a study came out that made a lot of people concerned about fish oil supplements and cancer. The study, published in the Journal of the National Cancer Institute, showed that men who consume the largest amount of fish oil had a 71 percent higher risk of high-grade prostate cancer and a 43 percent increase in all types of prostate cancer. The study was conducted on 2,227 men, of which 38 percent of the men already had prostate cancer. (39)

Another small study had all volunteers consume the same exact control diet and substituted fish oil for visible fats (things like butter and cream). The volunteers consumed six grams of fish oil each day for three weeks. They found that body fat mass decreased with the intake of fish oil. The researchers conclude that dietary fish oil reduces body fat and stimulates the use of fatty acids for the production of energy in healthy adults. (33a)
Mozaffarian D, Marchioli R, Macchia A, Silletta MG, Ferrazzi P, Gardner TJ, Latini R, Libby P, Lombardi F, O'Gara PT, Page RL, Tavazzi L, Tognoni G; OPERA Investigators. Fish oil and postoperative atrial fibrillation: the Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial. JAMA 2012;308(19):2001-11. View abstract.

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.

Hooper, L., Thompson, R. L., Harrison, R. A., Summerbell, C. D., Ness, A. R., Moore, H. J., Worthington, H. V., Durrington, P. N., Higgins, J. P., Capps, N. E., Riemersma, R. A., Ebrahim, S. B., and Davey, Smith G. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ 4-1-2006;332(7544):752-760. View abstract.


(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.)
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.
Omega-3 fatty acids have been found to play a role in atherosclerosis and peripheral arterial disease (PAD). It is thought that both EPA and DHA improve plaque stability, decrease endothelial activation, and improve vascular permeability, thereby decreasing the chance of experiencing a cardiovascular event (41). It was found that EPA supplementation is associated with significantly higher amounts of EPA in the carotid plaque than placebo (P < 0.0001), which may lead to decreased plaque inflammation and increased stability (42). PAD, a manifestation of atherosclerosis, is characterized by buildup of plaque in the arteries of the leg and can eventually lead to complete blockage of the arteries. EPA+DHA supplementation has been shown to improve endothelial function in patients with PAD by decreasing plasma levels of soluble thrombomodulin from a median value of 33.0 μg/L to 17.0 μg/L (P = 0.04) and improve brachial artery flow–mediated dilation from 6.7% to 10.0% (P = 0.02) (43). Patients who had PAD and were supplemented with EPA experienced a significantly lower major coronary event HR than those who did not take EPA (HR: 0.44; 95% CI: 0.19–0.97; P = 0.041) (44).
If you want to take higher doses of omega-3 fish oil supplements, talk to your doctor first. Your doctor can guide you in supplementing your diet with omega-3 fish oil. Also, your doctor can monitor all aspects of your health if you take higher doses of fish oil.For people with very high triglyceride levels, prescription omega-3 preparations are also available.
Damage to the kidneys caused the drug cyclosporine. Cyclosporine is a medication that reduces the chance of organ rejection after an organ transplant. Taking fish oil seems to prevent kidney damage in people taking this drug. Fish oil also seems to improve kidney function during the recovery phase following the rejection of a transplanted organ in people taking cyclosporine.
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