A group out of India conducted a study published in Cancer Chemotherapy and Pharmacology based on the premise that “fish oil rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize tumor cells to anti-cancer drugs.” The study found that using 5-Fluorouracil (5-FU) to treat colorectal cancer along with fish oil increased the survival rate in carcinogen-treated animals. Researchers also found that the fish oil ameliorated hematologic depression, along with gastrointestinal, hepatic and renal toxicity caused by the 5-FU. (15)
A group out of India conducted a study published in Cancer Chemotherapy and Pharmacology based on the premise that “fish oil rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize tumor cells to anti-cancer drugs.” The study found that using 5-Fluorouracil (5-FU) to treat colorectal cancer along with fish oil increased the survival rate in carcinogen-treated animals. Researchers also found that the fish oil ameliorated hematologic depression, along with gastrointestinal, hepatic and renal toxicity caused by the 5-FU. (15)
Omega-3 fatty acids are found primarily in fish oil and certain marine algae. Because depression appears less common in nations where people eat large amounts of fish, scientists have investigated whether fish oils may prevent and/or treat depression and other mood disorders. Two omega-3 fatty acids — eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) — are thought to have the most potential to benefit people with mood disorders.
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) has been used once daily for 90 days.
While fish oil has plenty of beneficial qualities, there is a lot of hype around its possible applications, and not all of them are accurate, so be wary when reading literature on this useful oil. Fish oil manufacturers have attempted to market it as a remedy for almost anything. We suggest that readers educate themselves fully before making an informed decision, rather than getting affected by both negative and positive propaganda about the beneficial applications of fish oil.
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]
Human studies also confirm cognition and memory improvement with omega-3 supplementation. For example, a study showed that both fish oil and krill oil enhanced cognitive function in a group of older men by increasing oxygen delivery to their brains. Interestingly, for those taking krill oil this effect was more prominent than those taking fish oil, though both groups were significantly better than placebo.30 As we pointed out earlier, because the omega-3 DHA is bound to phospholipids in krill it may be more effectively incorporated into the critical cell membrane in brain cells.
However, the researchers do have some good news. They concluded that omega 3 fatty acids do appear to reduce the type of blood cholesterol known as triglycerides, but that supplements probably are not useful for preventing or improving heart and circulatory problems. And, upping your intake of plant-based omega 3s high in ALA (ie, walnuts, flaxseed and flax oil, chia seeds) may help your heart somewhat.2
Oe, H., Hozumi, T., Murata, E., Matsuura, H., Negishi, K., Matsumura, Y., Iwata, S., Ogawa, K., Sugioka, K., Takemoto, Y., Shimada, K., Yoshiyama, M., Ishikura, Y., Kiso, Y., and Yoshikawa, J. Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals. Heart 2008;94(3):316-321. View abstract.

Widenhorn-Müller  K, Schwanda  S, Scholz  E, Spitzer  M, Bode  H.  Effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): a randomized placebo-controlled intervention trial.  Prostaglandins Leukot Essent Fatty Acids. 2014;91(1-2):49-60. doi:10.1016/j.plefa.2014.04.004PubMedGoogle ScholarCrossref
Matsumura  K, Noguchi  H, Nishi  D, Hamazaki  K, Hamazaki  T, Matsuoka  YJ.  Effects of omega-3 polyunsaturated fatty acids on psychophysiological symptoms of post-traumatic stress disorder in accident survivors: a randomized, double-blind, placebo-controlled trial.  J Affect Disord. 2017;224:27-31. doi:10.1016/j.jad.2016.05.054PubMedGoogle ScholarCrossref
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.
It is well known that fish oil has the ability to improve vision. It also helps in avoiding age-related macular degeneration. The National Eye Institute at the National Institute of Health in the United States plans to conduct a nationwide study to evaluate the effect of fish oil in treating macular degeneration. This study will provide strong scientific evidence regarding the benefits of fish oil for eye care, thereby allowing government agencies and physicians to strongly recommend fish oil for macular degeneration.
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As mentioned above, the omega-3 index has been suggested as a predictor of the risk of coronary heart disease and other cardiovascular events. One study on a population in Seattle found that people with low omega-3 index levels were 10 times as likely to die from sudden cardiac death compared to people with higher omega-3 index levels (13). The NIH-funded Framingham study referenced above showed that the people with the highest omega-3 index levels had a 33% reduction in risk of death from any cause compared to the people with the lowest levels (2). In addition, a new study focused on individuals age 25 to 41 found that higher omega-3 index levels were associated with lower blood pressure in healthy adults (14).
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.

Khandelwal, S., Demonty, I., Jeemon, P., Lakshmy, R., Mukherjee, R., Gupta, R., Snehi, U., Niveditha, D., Singh, Y., van der Knaap, H. C., Passi, S. J., Prabhakaran, D., and Reddy, K. S. Independent and interactive effects of plant sterols and fish oil n-3 long-chain polyunsaturated fatty acids on the plasma lipid profile of mildly hyperlipidaemic Indian adults. Br.J.Nutr. 2009;102(5):722-732. View abstract.
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Fish oil’s most potent effect on atherosclerosis may be related to its potential to alter plaque inflammation, thereby stabilizing vulnerable plaques. In recent years there has been a growing body of evidence that is shifting the paradigm of how inflammation is contained and dissipated.4 In this new model, inflammation resolution is an active process mediated by lipid-derived compounds. Newly discovered families of chemical mediators, resolvins, and protectins5,6 are directly involved in blocking neutrophil migration, infiltration, and recruitment, as well as in blocking T-cell migration and promoting T-cell apoptosis.7–12 In addition, protectins can reduce tumor necrosis factor and interferon secretion.13 Interestingly, both protectins and resolvins are strictly derived from omega-3 FA. EPA is the substrate of the resolvins family and DHA can be converted to both resolvins and protectins.7 It may be that the effects of fish oil on inflammatory mediators underlie the positive findings demonstrated in several trials assessing fish oil and plaque stability.14–16
An analysis based on data from the Norwegian Women and Cancer Study (NOWAC) with regards to the dangers of persistent organic pollutants (POPs) in cod liver came to the conclusion that "in Norwegian women, fish liver consumption was not associated with an increased cancer risk in breast, uterus, or colon. In contrast, a decreased risk for total cancer was found."[65]

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Fish or seafood allergy: Some people who are allergic to seafood such as fish might also be allergic to fish oil supplements. There is no reliable information showing how likely people with seafood allergy are to have an allergic reaction to fish oil. Until more is known, advise patients allergic to seafood to avoid or use fish oil supplements cautiously.
Sangiovanni, J. P., Agron, E., Meleth, A. D., Reed, G. F., Sperduto, R. D., Clemons, T. E., and Chew, E. Y. {omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study. Am J Clin Nutr 2009;90(6):1601-1607. View abstract.
Typical Western diets provide ratios of between 10:1 and 30:1 (i.e., dramatically higher levels of omega−6 than omega−3).[92] The ratios of omega−6 to omega−3 fatty acids in some common vegetable oils are: canola 2:1, hemp 2–3:1,[93] soybean 7:1, olive 3–13:1, sunflower (no omega−3), flax 1:3,[94] cottonseed (almost no omega−3), peanut (no omega−3), grapeseed oil (almost no omega−3) and corn oil 46:1.[95]
To avoid fish oil supplements containing mercury or other harmful contaminants, purchase supplements from a reputable source that clearly tests for these health-hazardous contaminants in its products. These tests should be ideally conducted by a third-party, and a certificate of analysis should indicate the levels of purity from environmental toxins.
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.
In lab experiments, animals given krill showed improved navigation skills. What this means is that they achieved higher levels of cognition and memory required to navigate complex territory.28 In addition, research shows that animals supplemented with krill oil showed significantly fewer signs of depression and resignation. This improvement in mood was equivalent to the effect of the prescription anti-depressant drug imipramine (Tofranil®).29
Eicosatetraenoic Acid (ETA): ETA is a lesser-known omega-3 fatty acid that also contains 20 carbons, like EPA, but only four bonds instead of five. It is found richly inroe oil and green-lipped mussel and is only recently being recognized for its potent health benefits. Not only is it anti-inflammatory, like the other omega-3s, but ETA can also limit your body’s production of the inflammatory omega-6 fatty acid arachidonic acid (ARA). In fact, ETA redirects the enzyme that normally creates ARA to convert it to EPA instead!
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.

If you find yourself in a position where you are just not eating any of these foods, and you want to get enough omega-3 fatty acids, then I think fish oil is okay, but I would limit not the amount of fish oil but the amount listed on the label of EPA and DHA combined. I would limit that amount to around 250 milligrams per day because I don’t think most people need more than that. Some signs that you might not be getting enough omega-3 fatty acids include chronic low-grade inflammation, poor visual acuity, slower mental processing, trouble learning, and possibly Alzheimer’s disease and psychiatric conditions, like depression, anxiety, and attention deficit and hyperactivity disorder, ADHD.
Increasing ALA intake probably makes little or no difference to all‐cause mortality (RR 1.01, 95% CI 0.84 to 1.20, 19,327 participants; 459 deaths, 5 RCTs),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25, 18,619 participants; 219 cardiovascular deaths, 4 RCTs), and it may make little or no difference to CHD events (RR 1.00, 95% CI 0.80 to 1.22, 19,061 participants, 397 CHD events, 4 RCTs, low‐quality evidence). However, increased ALA may slightly reduce risk of cardiovascular events (from 4.8% to 4.7%, RR 0.95, 95% CI 0.83 to 1.07, 19,327 participants; 884 CVD events, 5 RCTs, low‐quality evidence), and probably reduces risk of CHD mortality (1.1% to 1.0%, RR 0.95, 95% CI 0.72 to 1.26, 18,353 participants; 193 CHD deaths, 3 RCTs), and arrhythmia (3.3% to 2.6%, RR 0.79, 95% CI 0.57 to 1.10, 4,837 participants; 141 events, 1 RCT). Effects on stroke are unclear.
Given the wide-ranging importance and benefits of marine omega-3 fatty acids, it is important to eat fish or other seafood one to two times per week, particularly fatty (dark meat) fish that are richer in EPA and DHA. This is especially important for women who are pregnant or hoping to become pregnant and nursing mothers. From the third trimester until the second year of life, a developing child needs a steady supply of DHA to form the brain and other parts of the nervous system. Many women shy away from eating fish because of concerns that mercury and other possible contaminants might harm their babies, (9) yet the evidence for harm from lack of omega-3 fats is far more consistent, and a balance of benefit vs. risk is easily obtained. (To learn more about the controversy over contaminants in fatty fish, read Fish: Friend or Foe.)

• Fish oil – Fish oil is among the primary ways that people enhance their intake of omega-3 fats. High-quality fish oils can certainly provide many health benefits. However, this oil is weak in antioxidants. This means that as you increase your omega-3 intake through fish oil consumption, you actually increase your need for added antioxidant protection.
Nielsen, G. L., Faarvang, K. L., Thomsen, B. S., Teglbjaerg, K. L., Jensen, L. T., Hansen, T. M., Lervang, H. H., Schmidt, E. B., Dyerberg, J., and Ernst, E. The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial. Eur J Clin Invest 1992;22(10):687-691. View abstract.
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