Corresponding Author: Yutaka J. Matsuoka, MD, PhD, Division of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan (yumatsuo@ncc.go.jp); Kuan-Pin Su, MD, PhD, China Medical University Hospital, No. 2, Yude Road, North District, Taichung City, Taiwan 404 (cobolsu@gmail.com).
Corresponding Author: Yutaka J. Matsuoka, MD, PhD, Division of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan (yumatsuo@ncc.go.jp); Kuan-Pin Su, MD, PhD, China Medical University Hospital, No. 2, Yude Road, North District, Taichung City, Taiwan 404 (cobolsu@gmail.com).
An 18-month study was published in 2014 that evaluated how borage seed oil — rich in GLA — and fish oil rich fared against each other in treating patients with rheumatoid arthritis. It was discovered that all three groups (one taking fish oil, one taking borage oil and one taking a combination of the two) “exhibited significant reductions” in disease activity, and no therapy outperformed the others. For all three, “meaningful clinical responses” were the same after nine months. (11)
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
"All these diseases have a common genesis in inflammation," says Joseph C. Maroon, MD, professor and vice chairman of the department of neurological surgery at the University of Pittsburgh School of Medicine. Co-author of Fish Oil: The Natural Anti-Inflammatory, Maroon says that in large enough amountsomega-3's reduce the inflammatory process that leads to many chronic conditions.

Abnormal cholesterol or fat levels in the blood (dyslipidemia). There is conflicting evidence about the effects of fish oil on cholesterol and fat levels in the blood. Some research shows that taking fish oil can lower triglyceride levels, low density lipoprotein (LDL or "bad") cholesterol, and increase high density lipoprotein (HDL or "good") cholesterol in people with abnormal cholesterol levels. However, other research shows that taking fish oil daily does not have this effect.
Krill oil is a source of omega−3 fatty acids.[116] The effect of krill oil, at a lower dose of EPA + DHA (62.8%), was demonstrated to be similar to that of fish oil on blood lipid levels and markers of inflammation in healthy humans.[117] While not an endangered species, krill are a mainstay of the diets of many ocean-based species including whales, causing environmental and scientific concerns about their sustainability.[118][119][120]
When taking fish oil, more is not always better. Remember that you want it to stay in a balanced ratio with omega-6 fats. For most people, I recommend a 1,000-milligram dose of fish oil daily as a good amount and the most scientifically studied dosage. I highly recommend not taking more than that unless directed to under the supervision of a doctor.
Boucher, O., Burden, M. J., Muckle, G., Saint-Amour, D., Ayotte, P., Dewailly, E. ... Jacobson, J. L.. (2011, May). Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age. American Journal of Clinical Nutrition 93(5), 1025-1037. Retrieved from http://ajcn.nutrition.org/content/93/5/1025.full

It is also believed that women who do not have a sufficient intake of EPA and DHA in their diet suffer from depression after childbirth, as there is a transfer of some amount of brain mass from the mother to the child in the last stages of pregnancy. Thus, it is very beneficial to consume fish oil either by eating fish or taking fish oil supplements, tablets, capsules, or pills during pregnancy for the overall development of the child and the well-being of the mother. However, it should be noted that fish oil obtained from the liver of the fish, example – cod liver oil, should not be consumed during pregnancy as cod liver oil is high in retinol and vitamin A, which are usually known to cause birth defects.
Fish oil is also commonly used to treat conditions such as Rheumatoid arthritis, high blood pressure, ADHD, menstrual pain, hardening of the arteries or kidney problems. These conditions can be improved by improving blood flow, which omega-3 fatty acids in the blood stream. There is also some evidence that fish oil may help with conditions such as chest pain, liver disease, migraine prevention, gum infections, breast pain, and muscle soreness due to exercise, skin rashes and stomach ulcers.
Jump up ^ Martins, Julian G (2009). "EPA but Not DHA Appears to Be Responsible for the Efficacy of Omega-3 Long Chain Polyunsaturated Fatty Acid Supplementation in Depression: Evidence from a Meta-Analysis of Randomized Controlled Trials". Journal of the American College of Nutrition. 28 (5): 525–42. doi:10.1080/07315724.2009.10719785. PMID 20439549.
Fish and omega-3 fatty acids. If you keep up with the latest nutrition news, you may have a pretty good sense of what they offer. But, if you're like many people, you still can't tell your omega-3s from your omega-6s -- and you sure as heck can't pronounce eicosapentaenoic acid. That's OK. Our fishing expedition turned up some interesting facts to share about omega-3 fatty acids and fish.
I've done a lot of shopping and comparing of fish oil softgels and have reached the conclusion that these are these best you can buy. Prior to seeing these in my chiropractor's office I scanned the labels and specs on many brands at Mothers, Vitamin Shoppe, Sprouts and Amazon vendors. These have 430 mg of EPA and 290 mg of DHA per softgel, with a recommended dose of two.. If you compare as well, you will find most other brands, including those sold as premium products at health food stores at premium prices don't have the same potency.Especially among Krill Oil products. My chiropractor shared a clinical study that showed taking fish oil containing levels of EPA and DHA consistent with these supplements caused participants to say it had the same favorable affect as taking ibuprofen. I make no claims. I am not a doctor, am not associated ... full review
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]
These low levels are especially bad when compared to the numbers from the Japanese population. In Japan, the average omega-3 index level is more than double that of the average American, with some surveys showing Japanese men consume over 100 g (approximately 3.5 oz) of fish every day. These radically different dietary habits help explain how even those with omega-3 indexes in the lowest 5th percentile of the Japanese population have higher omega-3 index averages than most Americans (8).
When it comes to omega-3 benefits, there are rarely nutrients that pack this many positive health outcomes into one compound. The most commonly known benefit of omega-3s is a reduced risk of heart disease, but that’s not the only studied plus of getting lots of omega-3s in your diet — from fetal development to retinal function to weight management (and a lot more in between), these acids support and promote optimal health for anyone. (1)
Bianconi, L., Calo, L., Mennuni, M., Santini, L., Morosetti, P., Azzolini, P., Barbato, G., Biscione, F., Romano, P., and Santini, M. n-3 polyunsaturated fatty acids for the prevention of arrhythmia recurrence after electrical cardioversion of chronic persistent atrial fibrillation: a randomized, double-blind, multicentre study. Europace. 2011;13(2):174-181. View abstract.
The competition between EPA and DHA during digestion and absorption and the fact that DHA appears to ‘block’ the therapeutic actions of EPA can therefore be an issue if we are looking to optimise the benefits associated with EPA (Martins 2009; Bloch & Qawasmi et al, 2011; Sublette et al, 2011). High dose, high concentration and high ratio EPA supplements increase the effectiveness in depression studies, and pure EPA-only is optimal. Depression is also a condition with an inflammatory basis, so this is likely another significant reason for EPA being the key player – its antagonistic relationship with the inflammatory omega-3 AA (arachidonic acid) is very effective at reducing inflammation.
What about blood clotting? Circulating cells called platelets are critical in causing your blood to clot. When platelets are activated, they aggregate and cause clots. If these clots occur in particularly sensitive regions of your body, they can lead to a heart attack or stroke. EPA reduces platelet activation, an early step in platelet aggregation to help to reduce clotting. One study found that EPA was superior to DHA in decreasing platelet activation, a precursor to blood clotting.1
According to the Cardiovascular Research Institute in Maastricht in Netherlands, “Epidemiological studies show that replacing fat with carbohydrates may even be worse [than the Western-type high-fat diet] and that various polyunsaturated fatty acids (FA) have beneficial rather than detrimental effects on CVD (cardiovascular disease) outcome.” This includes fish-oil fatty acids with anti-inflammatory properties, which can help prevent and reverse a plethora of cardiovascular diseases. (19)
Additional side effects of fish oil supplements which have been reported include headache, short-term memory loss, depression, somatic disorders, and increased risk of colon cancer, nasopharyngitis, worsening of asthma symptoms, hemolytic anemia, decreased physical activity, increased appetite, a general uncomfortable feeling or increased blood pressure. The percentage of users that develop these side effects is not known. If these side effects become severe it is recommended that you stop using fish oil supplements.
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.
Omega−3 fatty acids are important for normal metabolism.[8] Mammals are unable to synthesize omega−3 fatty acids, but can obtain the shorter-chain omega−3 fatty acid ALA (18 carbons and 3 double bonds) through diet and use it to form the more important long-chain omega−3 fatty acids, EPA (20 carbons and 5 double bonds) and then from EPA, the most crucial, DHA (22 carbons and 6 double bonds).[8] The ability to make the longer-chain omega−3 fatty acids from ALA may be impaired in aging.[9][10] In foods exposed to air, unsaturated fatty acids are vulnerable to oxidation and rancidity.[11]

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


In fact, fish oil is even dipping its way into mainstream medicine. In September 2018, Amarin Corporation, the biopharmaceutical developer of pharmaceutical-grade fish oil Vascepa, released preliminary findings of its double-blind clinical trial. In the study, researchers tracked more than 8,000 adults for a median 4.9 years. The mix of study participants had either established cardiovascular disease or type 2 diabetes and another cardiovascular disease risk factor, along with persistently elevated triglycerides.
Higdon JV, Liu J, Du S, et al. Supplementation of postmenopausal women with fish oil rich in eicosapentaenoic acid and docosahexaenoic acid is not associated with greater in vivo lipid peroxidation compared with oils rich in oleate and linoleate as assessed by plasma malondialdehyde and F(2)- isoprostanes. Am J Clin Nutr 2000;72:714-22. View abstract.

Docosahexaenoic acid (DHA) found primarily in fish oil, this is the ultimate form of fatty acid in humans. Most people get far too little of this all-important fatty acid, especially since the conversion of ALA to DHA is slow and minimally yielding. Getting a daily dose of of DHA (600 to 1000 mg) from supplements is preferable to reap the health benefits. You have a choice of taking a fish oil supplement or one derived from algae or krill, a shrimp-like crustacean.
Several studies confirmed the benefit of omega-3 supplementation during pregnancy in terms of proper development of the brain and retina. Of the 2 most important long-chain omega-3 fatty acids, EPA and DHA, DHA is the more important for proper cell membrane function and is vital to the development of the fetal brain and retina (17). During the third trimester, vast amounts of DHA accumulate in fetal tissue (20). The 2 most infiltrated fetal areas include the retina and brain, which may correlate with normal eyesight and brain function (19). A study by Judge et al. (20) found that children whose mothers had taken DHA supplementation during pregnancy (n = 29) had significantly better problem-solving skills at 9 mo old (P = 0.017) than those whose mothers had not taken DHA supplementation during pregnancy (n = 15). Another study provided a cognitive assessment of children 2.5 y after maternal EPA+DHA supplementation during pregnancy from 20 wk of gestation until delivery (n = 33) compared with children in a placebo group (n = 39). Children in the EPA + DHA–supplemented group attained significantly higher scores for eye and hand coordination [mean score, 114 (SD 10.2] than those in the placebo group [mean score, 108 (SD 11.3)] (P = 0.021, adjusted P = 0.008) (19).
Unsafe for children. Fish oil supplements are not considered safe for children. Too much of this fat in their system can lead to a chemical imbalance in the brain which could stunt healthy growth and development. Because of this, and the possible exposure to polychlorinated biphenyls, methylmercury and other toxins which are found in some sources of fish, it is not recommended that women who are pregnant take excessive amounts of fish oil. Servings of fish should be limited to six ounces per week and they should refrain from using fish oil or other fatty acid supplement pills. Children should not consume more than two ounces of fish per week to avoid overexposure to these chemicals. Now you know although fish oil can benefit human beings a lot, fish oil side effects should never be neglected for the sake of your safety. 
RA causes chronic pain, swelling, stiffness, and loss of function in the joints. Some clinical trials have shown that taking omega-3 supplements may help manage RA when taken together with standard RA medications and other treatments. For example, people with RA who take omega-3 supplements may need less pain-relief medication, but it is not clear if the supplements reduce joint pain, swelling, or morning stiffness.
The biggest cause of omega-3 deficiency is the overconsumption of foods high in omega-6 fatty acids. Omega-6 comes from things like fried foods, fast foods and boxed foods that contain vegetables oils like soybean oil, canola oil, sunflower oil, cottonseed oil and corn oil. When you consume too much omega-6, it can decrease your body’s ability to metabolize healthy omega-3 fatty acids. (36)

Your concerns are very valid. The quality of commercially available omega-3 preparations can vary greatly. In our clinical trials we use preparations made by reputable manufacturers with high standards. We also have the preparations analyzed by 2 independent labs to confirm omega-3 content, impurities, and degree of oxidation, prior to initiating the study. While omega-3 fatty acids–like most nutrients–are ideally obtained through dietary practice, because many people may not enjoy omega-3 containing foods, supplements may be a good option for these individuals. Anyone who is interested in using an omega-3 preparation for treating a psychiatric condition should do so preferably under the supervision of a psychiatrist.
Brain function and vision rely on dietary intake of DHA to support a broad range of cell membrane properties, particularly in grey matter, which is rich in membranes.[61][62] A major structural component of the mammalian brain, DHA is the most abundant omega−3 fatty acid in the brain.[63] It is under study as a candidate essential nutrient with roles in neurodevelopment, cognition, and neurodegenerative disorders.[61]
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.
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