The association between supplementation and a lower risk of all-cause mortality appears inconclusive. Cancer The evidence linking the consumption of marine<unk> ts to a lower risk of cancer is poor. With the possible exception of breast cancer, there is insufficient evidence that supplementation with<unk> s has an effect on different cancers. The effect of consumption on prostate cancer is not conclusive. There is a decreased risk with higher blood levels of DPA, but possibly an increased risk of more aggressive prostate cancer was shown with higher blood levels of combined EPA and DHA. In people with advanced cancer and cachexia,<unk> s supplements may be of benefit, improving appetite, weight, and quality of life. Cardiovascular disease Moderate and high quality evidence from a 2020 review showed that EPA and DHA, such as that found in omega−3 polyunsaturated fatty acid supplements, does not appear to improve mortality or cardiovascular health. There is weak evidence indicating that α-linolenic acid may be associated with a small reduction in the risk of a cardiovascular event or the risk of arrhythmia. A 2018 meta-analysis found no support that daily intake of one gram of<unk>  in individuals with a history of coronary heart disease prevents fatal coronary heart disease, nonfatal myocardial infarction or any other vascular event. However,<unk>  supplementation greater than one gram daily for at least a year may be protective against cardiac death, sudden death, and myocardial infarction in people who have a history of cardiovascular disease. No protective effect against the development of stroke or all-cause mortality was seen in this population. A 2018 study found that omega−3 supplementation was helpful in protecting cardiac health in those who did not regularly eat fish, particularly in the African American population. Eating a diet high in fish that contain long chain<unk> s does appear to decrease the risk of stroke. Fish oil supplementation has not been shown to benefit revascularization or abnormal heart rhythms and has no effect on heart failure hospital admission rates. Furthermore, fish oil supplement studies have failed to support claims of preventing heart attacks or strokes. In the EU, a review by the European Medicines Agency of<unk>  medicines containing a combination of an ethyl ester of eicosapentaenoic acid and docosahexaenoic acid at a dose of 1 g per day concluded that these medicines are not effective in secondary prevention of heart problems in patients who have had a myocardial infarction. Evidence suggests that<unk> s modestly lower blood pressure (systolic and diastolic) in people with hypertension and in people with normal blood pressure.<unk> s can also reduce heart rate, an emerging risk factor. Some evidence suggests that people with certain circulatory problems, such as varicose veins, may benefit from the consumption of EPA and DHA, which may stimulate blood circulation and increase the breakdown of fibrin, a protein involved in blood clotting and scar formation.<unk> s reduce blood triglyceride levels, but do not significantly change the level of LDL cholesterol or HDL cholesterol. The American Heart Association position (2011) is that borderline elevated triglycerides, defined as 150–199 mg/dL, can be lowered by 0.5–1.0 grams of EPA and DHA per day; high triglycerides 200–499 mg/dL benefit from 1–2 g/day; and >500 mg/dL be treated under a physician's supervision with 2–4 g/day using a prescription product. In this population<unk>  supplementation decreases the risk of heart disease by about 25%. A 2019 review found that<unk>  supplements make little or no difference to cardiovascular mortality and that patients with myocardial infarction yield no benefit in taking the supplements. A 2021 review found that omega-3 supplementation did not affect cardiovascular disease outcomes. A 2021 meta-analysis showed that use of marine omega-3 supplementation was associated with an increased risk of atrial fibrillation, with the risk appearing to increase for doses greater than one gram per day. Stroke A 2019 Cochrane review found that the effect of omega−3 supplementation on stroke is unclear as there is insufficient high‐quality evidence. Inflammation A 2013 systematic review found tentative evidence of benefit for lowering inflammation levels in healthy adults and in people with one or more biomarkers of metabolic syndrome. Consumption of<unk> s from marine sources lowers blood markers of inflammation such as C-reactive protein, interleukin 6, and TNF alpha. For rheumatoid arthritis, one systematic review found consistent but modest, evidence for the effect of marine n−3 PUFAs on symptoms such as "joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity" as well as the use of non-steroidal anti-inflammatory drugs. The American College of Rheumatology has stated that there may be modest benefit from the use of fish oils, but that it may take months for effects to be seen, and cautions for possible gastrointestinal side effects and the possibility of the supplements containing mercury or vitamin A at toxic levels. The National Center for Complementary and Integrative Health has concluded that "supplements containing<unk> s... may help relieve rheumatoid arthritis symptoms" and warns that such supplements "may interact with drugs that affect blood clotting". Developmental disabilities One meta-analysis concluded that<unk>  supplementation demonstrated a modest effect for improving ADHD symptoms. A Cochrane review of PUFA (not necessarily omega−3) supplementation found "there is little evidence that PUFA supplementation provides any benefit for the symptoms of ADHD in children and adolescents", while a different review found "insufficient evidence to draw any conclusion about the use of PUFAs for children with specific learning disorders". Another review concluded that the evidence is inconclusive for the use of<unk> s in behavior and non-neurodegenerative neuropsychiatric disorders such as ADHD and depression. A 2015 meta-analysis of the effect of omega−3 supplementation during pregnancy did not demonstrate a decrease in the rate of preterm birth or improve outcomes in women with singleton pregnancies with no prior preterm births. A 2018 Cochrane systematic review with moderate to high quality of evidence suggested that<unk> s may reduce risk of perinatal death, risk of low body weight babies; and possibly mildly increased LGA babies. A 2021 umbrella review with moderate to high quality of evidence suggested that "omega-3 supplementation during pregnancy can exert favorable effects against pre-eclampsia, low-birth weight, pre-term delivery, and post-partum depression, and can improve anthropometric measures, immune system, and visual activity in infants and cardiometabolic risk factors in pregnant mothers." Mental health Omega-3 supplementation has not been shown to significantly affect symptoms of anxiety, major depressive disorder or schizophrenia. A 2021 Cochrane review concluded that there is not "sufficient high‐certainty evidence to determine the effects of n‐3PUFAs as a treatment for MDD".<unk> s have also been investigated as an add-on for the treatment of depression associated with bipolar disorder although there is limited data available. Two reviews have suggested that<unk>  supplementation significantly improves depressive symptoms in perinatal women. In contrast to dietary supplementation studies, there is significant difficulty in interpreting the literature regarding dietary intake of<unk> s (e.g. from fish) due to participant recall and systematic differences in diets. There is also controversy as to the efficacy of omega−3, with many meta-analysis papers finding heterogeneity among results which can be explained mostly by publication bias. A significant correlation between shorter treatment trials was associated with increased omega−3 efficacy for treating depressed symptoms further implicating bias in publication. Cognitive aging A 2016 Cochrane review found no convincing evidence for the use of omega‐3 PUFA supplements in treatment of Alzheimer's disease or dementia. There is preliminary evidence of effect on mild cognitive problems, but none supporting an effect in healthy people or those with dementia. A 2020 review suggested that omega<unk>  supplementation has no effect on global cognitive function but has a mild benefit in improving memory in non-demented adults. A 2022 looked at observational studies and randomized control trials. The authors see promising evidence for prevention of cognitive decline in people who regularly eat long-chain omega<unk>  rich foods. Conversely, clinical trials with participants already diagnosed with Alzheimer's show no effect. Brain and visual functions 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. A major structural component of the mammalian brain, DHA is the most abundant<unk>  in the brain. Omega<unk>  PUFA supplementation has no effect on macular degeneration or development of visual loss. Atopic diseases Results of studies investigating the role of LCPUFA supplementation and LCPUFA status in the prevention and therapy of atopic diseases (allergic rhinoconjunctivitis, atopic dermatitis, and allergic asthma) are controversial; therefore, it could not be stated either that the nutritional intake of n−3 fatty acids has a clear preventive or therapeutic role, or that the intake of n-6 fatty acids has a promoting role in the context of atopic diseases. Risk of deficiency People with PKU often have low intake of omega−3
Omega-3 fatty acid
Omega-6 fatty acid
Cholic acid
Omega-3 acid ethyl esters
Fish oil
Fish oil 
Phytosterol
Saturated fat