Since EPA and DHA are both essential for health and appear together in nature, many studies have attempted to treat clinical conditions with combined EPA and DHA oils, but the outcomes have been varied, contradictory and disappointing. Consequently, researchers have started to investigate the individual actions of EPA and DHA in isolation, in numerous health conditions where an omega-3 deficiency is related to symptoms or known to play a causative role. The emerging evidence shows marked differences between how these two fatty acids affect us – not just at the cellular level but also the body as a whole.
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.

Giacco, R., Cuomo, V., Vessby, B., Uusitupa, M., Hermansen, K., Meyer, B. J., Riccardi, G., and Rivellese, A. A. Fish oil, insulin sensitivity, insulin secretion and glucose tolerance in healthy people: is there any effect of fish oil supplementation in relation to the type of background diet and habitual dietary intake of n-6 and n-3 fatty acids? Nutr.Metab Cardiovasc.Dis. 2007;17(8):572-580. 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.

Fatty predatory fish like sharks, swordfish, tilefish, and albacore tuna may be high in omega-3 fatty acids, but due to their position at the top of the food chain, these species may also accumulate toxic substances through biomagnification. For this reason, the United States Environmental Protection Agency recommends limiting consumption (especially for women of childbearing age) of certain (predatory) fish species (e.g. albacore tuna, shark, king mackerel, tilefish and swordfish) due to high levels of the toxic contaminant mercury. Dioxin, PCBs and chlordane are also present.[13] Fish oil is used as a component in aquaculture feed. More than 50 percent of the world's fish oil used in aquaculture feed is fed to farmed salmon.[14]
Keep in mind that APA found in plant-based foods takes a lot of energy for your body to convert to EPA and DHA. I understand that many people following a vegan diet struggle with the concept of fish oil or eating fish, but animal products contain the necessary omega-3 fatty acids to allow your body to absorb and synthesize what you take in. However, there are plant-based options — you’ll just need more APA because of the way your body processes the medium-chain fatty acid.

Foods such as meat, eggs, fish and nuts contain omega-3 and omega-6 fatty acids, which the body converts into endocannabinoids – cannabinoids that the body produces naturally, said Aditi Das, a University of Illinois professor of comparative biosciences and biochemistry, who led the study. Cannabinoids in marijuana and endocannabinoids produced in the body can support the body’s immune system and therefore are attractive targets for the development of anti-inflammatory therapeutics, she said.

Jump up ^ Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J (July 2006). "n−3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review". The American Journal of Clinical Nutrition. 84 (1): 5–17. doi:10.1093/ajcn/84.1.5. PMID 16825676.

FDA pregnancy category C. It is not known whether Fish Oil will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using Fish Oil. It is not known whether omega-3 polyunsaturated fatty acids pass into breast milk or if this could harm a nursing baby. Do not use Fish Oil without telling your doctor if you are breast-feeding a baby. Do not give this medication to anyone under 18 years old.


Among the 16 studies comparing the effect of omega-3 PUFA treatment with that of the placebo,33,34,36,47-49,51-53,55-61 the main results revealed a significantly greater association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 16; Hedges g, 0.372; 95% CI, 0.032-0.712; P = .03; eFigure 3 in the Supplement). The meta-analysis of the subgroup focusing on non–placebo-controlled trials also showed a significantly greater association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 3; Hedges g, 0.399; 95% CI, 0.154-0.643; P = .001).35,50,54
Animal studies show potent reduction of liver fat stores, glucose levels, and cholesterol levels in mice supplemented with krill oil while being fed a high fat diet.64,65 While many of these effects are seen with fish oil as well, studies show that krill oil, with its unique phospholipid structure, had the added benefit of increasing fat-burning in mitochondria while reducing new glucose production in the liver.66,67 As with so many other complex disease processes, utilizing multiple pathways to reduce disease is a highly effective strategy.67
Cochrane lead author, Dr. Lee Hooper from the University of East Anglia, UK said: “We can be confident in the findings of this review which go against the popular belief that long-chain omega 3 supplements protect the heart. This large systematic review included information from many thousands of people over long periods.  Despite all this information, we don’t see protective effects.

The conversion of ALA to EPA and further to DHA in humans has been reported to be limited, but varies with individuals.[79][80] Women have higher ALA-to-DHA conversion efficiency than men, which is presumed[81] to be due to the lower rate of use of dietary ALA for beta-oxidation. One preliminary study showed that EPA can be increased by lowering the amount of dietary linoleic acid, and DHA can be increased by elevating intake of dietary ALA.[82]
Omega 3 fatty acids—found in supplements and naturally in some foods like certain fish, and nuts and seeds—have long been touted for their health benefits, especially heart health. Yet, a lot is still unknown, including whether it's better to get your omega 3 fats from pills or in food—and the debate continues regarding how much they may actually help you avoid heart disease.
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.

The Japanese notably have the lowest levels of coronary heart disease mortality and atherosclerosis among developed nations — a phenomena that has been largely subscribed to diet. However, even within Japan, a 10-year study of over 41,000 people found that higher intakes of omega-3s were associated with lower risks of nonfatal coronary events (8). A more recent study also found that Japanese with higher omega-3 index levels (10%) had a lower risk of fatal coronary heart disease than those with a lower omega-3 index levels (8%) (9). The study begs the question of whether maybe even the Japanese have room to improve their omega-3 intake and whether 8% should be considered the lower limit of a desirable range.
A scientific review in 2014 evaluated study findings on omega-3 intake in relation to the prevention and treatment of breast cancer, the most prevalent cancer among women. The review found that EPA and DHA, as well as ALA, can differentially inhibit breast tumor development. According to this review, there is solid evidence to support the use of omega-3s as “a nutritional intervention in the treatment of breast cancer to enhance conventional therapeutics, or potentially lowering effective doses.” (16) Additionally, a 2016 study found that “very high fish consumption in early adulthood to midlife may be associated with decreased risk of breast cancer.” (17)
Although there are no randomized data on fish oil consumption and protection from sudden death, observational studies have linked omega-3 FA with the prevention of sudden death. In a population-based, case-control study of sudden cardiac death victims, the mean red blood cell membrane omega-3 FA level of the lowest quartile, when compared with the mean level of the third quartile, was associated with a relative risk reduction of 70%.33 A similar finding was appreciated in a nested, prospective, case-control study of the Physician Health Study cohort of 22,000 healthy males. In the 119 patients that succumbed to sudden death, baseline omega-3 FA blood levels were significantly lower than in matched controls.34 Finally, in an analysis of data from the Nurses Health Study, a cohort study of 84,688 women, an inverse association was shown between fish consumption and CAD-related death. The investigators concluded that the reduction in CAD deaths was likely due to a reduction in sudden deaths, as there was no difference in the rate of MI when comparing high and low fish consumption.35
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]
Results  In total, 1203 participants with omega-3 PUFA treatment (mean age, 43.7 years; mean female proportion, 55.0%; mean omega-3 PUFA dosage, 1605.7 mg/d) and 1037 participants without omega-3 PUFA treatment (mean age, 40.6 years; mean female proportion, 55.0%) showed an association between clinical anxiety symptoms among participants with omega-3 PUFA treatment compared with control arms (Hedges g, 0.374; 95% CI, 0.081-0.666; P = .01). Subgroup analysis showed that the association of treatment with reduced anxiety symptoms was significantly greater in subgroups with specific clinical diagnoses than in subgroups without clinical conditions. The anxiolytic effect of omega-3 PUFAs was significantly better than that of controls only in subgroups with a higher dosage (at least 2000 mg/d) and not in subgroups with a lower dosage (<2000 mg/d).
There was no significant association between the Hedges g and mean age (k, 17; P = .51), female proportion (k, 18; P = .32), mean omega-3 PUFA dosage (k, 19; P = .307), EPA to DHA ratio (k, 17; P = .86), dropout rate in the omega-3 PUFA group (k, 18; P = .71), duration of omega-3 PUFA treatment (k, 19; P = .14), Jadad score of randomization (k, 19; P = .10), Jadad score of blindness (k, 19; P = .57), or total Jadad score (k, 19; P = .18).
Jump up ^ Abdelhamid, Asmaa S; Brown, Tracey J; Brainard, Julii S; Biswas, Priti; Thorpe, Gabrielle C; Moore, Helen J; Deane, Katherine HO; AlAbdulghafoor, Fai K; Summerbell, Carolyn D; Worthington, Helen V; Song, Fujian; Hooper, Lee (18 July 2018). "Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD003177.pub3.
^ Jump up to: a b c Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, Geleijnse JM, Rauch B, Ness A, Galan P, Chew EY, Bosch J, Collins R, Lewington S, Armitage J, Clarke R (March 2018). "Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals". JAMA Cardiology. 3 (3): 225–34. doi:10.1001/jamacardio.2017.5205. PMC 5885893. PMID 29387889.

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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 a chicken eats a diet heavy in omega-3s — such as flaxseed and other nutrient-dense grains — its eggs will be fortified with higher levels of those healthy fatty acids. If you can afford a little extra expense, look for omega-3-enriched eggs from humanely raised chickens that roam free and forage for insects and plants, which give the eggs even further nutrients and health benefits.
Many studies show that eating fatty fish and other types of seafood as part of a healthy eating pattern helps keep your heart healthy and helps protect you from many heart problems. Getting more EPA or DHA from foods lowers triglyceride levels, for example. Omega-3 dietary supplements can also help lower triglyceride levels, but it is not clear whether omega-3 supplements protect you from most heart problems.
Is krill oil better than fish oil for omega-3? Krill oil and fish oil are popular dietary supplements containing omega-3. Krill oil comes from a small crustacean while fish oil comes from oily fish, such as salmon. Both are shown to increase blood levels of omega-3 and have benefits for health. Learn more about the differences between krill oil and fish oil here. Read now
Since 2004, scientists have been suggesting that the omega-3 index be used as a way to measure a person’s risk of cardiovascular disease, in a similar way to how cholesterol levels are used today (1). A recent study funded by the National Institutes for Health even indicated that the omega-3 index could be a better predictor of death risk than serum cholesterol levels (2).
Five studies with 7 data sets recruited participants without specific clinical conditions.36,47,51,55,60 The main results revealed that there was no significant difference in the association of treatment with reduced anxiety symptoms between patients receiving omega-3 PUFA treatment and those not receiving it (k, 5; Hedges g, –0.008; 95% CI, –0.266 to 0.250; P = .95) (Figure 3A). Fourteen studies with 14 data sets recruited participants with specific clinical diagnoses.33-35,48-50,52-54,56-59,61 The main results revealed a significantly greater association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 14; Hedges g, 0.512; 95% CI, 0.119-0.906; P = .01) (Figure 3A). Furthermore, according to the interaction test, the association of omega-3 PUFA treatment with reduced anxiety symptoms was significantly stronger in subgroups with specific clinical diagnoses than in subgroups without specific clinical conditions (P = .03).
We’ve written about the dose necessary to achieve measurable benefits before. However, a person’s actual omega-3 intake can be tricky to estimate. Even if you eat at least two servings of fatty fish per week, as the American Heart Association recommends (10), your fish might contain more or less omega-3s depending on the fish species, the time of year, and how you cook it. Even taking fish oil supplements isn’t always straightforward, as dose can be impacted by numerous bioavailability factors, as well as genetics, age, gender, medication-use and lifestyle.
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Omega-3s have been studied in various mood disorders, such as postpartum depression, with some promising results. In bipolar disorder (manic depression), the omega-3s may be most effective for the depressed phase rather than the manic phase of the illness. The omega-3s have also been proposed to alleviate or prevent other psychiatric conditions including schizophrenia, borderline personality disorder, obsessive compulsive disorder, and attention deficit disorder. However, there is still not enough evidence to recommend the omega-3s in these conditions.
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
Some research indicates that people who eat more seafood may have a reduced risk of cognitive decline. However, omega-3 supplements haven’t been shown to help prevent cognitive impairment or Alzheimer’s disease or to improve symptoms of these conditions. For example, a large NIH-sponsored study completed in 2015 indicated that taking EPA and DHA supplements did not slow cognitive decline in older adults. The people studied were participants in a larger eye disease study, and all of them had age-related macular degeneration (AMD). 
16. Saito Y, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, et al. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis. 2008;200:135–40. [PubMed]
The absence of DHA in many pure EPA trials, and therefore lack of competition between EPA and DHA during digestion and consequently for uptake, is considered to be partly responsible for the positive outcomes. Simply put, pure EPA delivers more EPA into cells where it is needed than combined EPA & DHA blends. Consequently, oils containing DHA may not be suitable for a variety of conditions when treatment relies on increasing levels of EPA and its end products.
Omega-3s have been studied for other conditions, with either inconclusive or negative results. These conditions include allergies, atopic eczema (an allergic skin condition), cystic fibrosis, diabetes, inflammatory bowel diseases (Crohn’s disease or ulcerative colitis), intermittent claudication (a circulatory problem), nonalcoholic fatty liver disease, and osteoporosis. 
Five studies with 7 data sets recruited participants without specific clinical conditions.36,47,51,55,60 The main results revealed that there was no significant difference in the association of treatment with reduced anxiety symptoms between patients receiving omega-3 PUFA treatment and those not receiving it (k, 5; Hedges g, –0.008; 95% CI, –0.266 to 0.250; P = .95) (Figure 3A). Fourteen studies with 14 data sets recruited participants with specific clinical diagnoses.33-35,48-50,52-54,56-59,61 The main results revealed a significantly greater association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 14; Hedges g, 0.512; 95% CI, 0.119-0.906; P = .01) (Figure 3A). Furthermore, according to the interaction test, the association of omega-3 PUFA treatment with reduced anxiety symptoms was significantly stronger in subgroups with specific clinical diagnoses than in subgroups without specific clinical conditions (P = .03).
The deficiency of EPA and DHA in diet contributes to skin conditions, such as dandruff, thinning hair, eczema and psoriasis, as well as age spots and sun spots. Without the essential fatty acids, too much moisture leaves the skin. The truth is your internal health can appear on your skin, and taking fish oil internally as a supplement may be as good as or better than applying conventional moisturizers.
The #1 Pharmacist Recommended Omega-3/Fish Oil brand,* Nature Made fish oil supply comes from deep ocean waters, not farm-raised fish. State-of-the-art purification processes remove mercury and ensure high levels of fish oil purity and concentration, guaranteed to pass the stringent standards of the Global Organization for EPA and DHA Omega-3 Voluntary Monograph.‡
Omega 3 fatty acids are monounsaturated fats that come from food sources—primarily cold water fish (eg, salmon, trout, tuna, mackerel, and herring)—that contain EPA (eicosapentaenoic acid) and docosahexaenoic acid (DHA). Other fatty acids are derived from plant-derived sources of food—including nuts (especially walnuts) and seeds (eg, flax, chia, sunflower)—that have primarily ALA (alpha-linolenic acid).
Chemical structure of alpha-linolenic acid (ALA), an essential omega−3 fatty acid, (18:3Δ9c,12c,15c, which means a chain of 18 carbons with 3 double bonds on carbons numbered 9, 12, and 15). Although chemists count from the carbonyl carbon (blue numbering), biologists count from the n (ω) carbon (red numbering). Note that, from the n end (diagram right), the first double bond appears as the third carbon-carbon bond (line segment), hence the name "n-3". This is explained by the fact that the n end is almost never changed during physiological transformations in the human body, as it is more energy-stable, and other compounds can be synthesized from the other carbonyl end, for example in glycerides, or from double bonds in the middle of the chain.
Pro Omega 3 Intensive Formula is a more convenient source of EPA and DHA than regular marine fish oils for those who would like to supplement their diets with higher amounts of these important omega 3 fatty acids. Our formula contains concentrated marine fish oil, providing enriched levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Plus, it’s lower in saturated fatty acids than regular marine fish oil. For those who don’t eat fish or want to add more omega to their diet, Omega 3 supplements are a convenient way of incorporating these important nutrients into your everyday life. This fish oil supplement is strictly screened for the absence of any toxic metals and chemicals, and is completely free of cholesterol. The oil is carefully processed and handled to avoid oxidation.†
A report by the Harvard Medical School studied five popular brands of fish oil, including Nordic Ultimate, Kirkland and CVS. They found that the brands had "negligible amounts of mercury, suggesting either that mercury is removed during the manufacturing of purified fish oil or that the fish sources used in these commercial preparations are relatively mercury-free".[66]

Meta‐analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all‐cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high‐quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high‐quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses – LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted.


The omega-3 PUFA EPA and DHA are important throughout life and are a dietary necessity found predominantly in fish and fish-oil supplements. The omega-3 fatty acids EPA and DHA are essential for proper fetal development, and supplementation during pregnancy has also been linked to decreased immune responses in infants including decreased incidence of allergies in infants. Omega-3 fatty acid consumption has been associated with improved cardiovascular function in terms of antiinflammatory properties, PAD, reduced major coronary events, and improved antiplatelet effects in the face of aspirin resistance or clopidogrel hyporesponsiveness. Patients with AD have been shown to be deficient in DHA, and supplementing them with EPA+DHA not only reverses this deficiency, but may also improve cognitive functioning in patients with very mild AD. With increasing rates of pediatric allergies, cardiovascular disease, and AD in the United States, EPA and DHA may be a safe and inexpensive link to a healthier life. Further research should be conducted in humans to assess a variety of clinical outcomes including quality of life and mental status. In addition, because potent lipid mediator metabolites of EPA and DHA are of great interest currently, their influence on these important outcomes should be assessed because current evidence suggests that their antiinflammatory and tissue-protective effects are nearly 1000 times greater than those of EPA and DHA (7).
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.
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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