A type of polyunsaturated fatty acid (PUFA) derived mainly from fish oil, omega-3 fatty acids are used as dietary supplements for depression, to lower cholesterol, and to reduce the risk of heart attack. 

A large survey of Finnish adults found that depressive symptoms were significantly higher among infrequent fish consumers ⁽¹⁾ and in other studies individuals with major depression had marked depletions in omega-3 ⁽²⁾. Supplementation, however, did not prevent depression ⁽⁷⁷⁾, relieve depression in adults with major depression ⁽³⁾, including those with or at risk of coronary heart disease ⁽⁶⁵⁾, with mild to moderate depression ⁽⁴⁾, with perinatal depression ⁽⁵⁾; or in obese or overweight adults with subsyndromal depressive symptoms ⁽⁶⁶⁾, and yielded mixed results in those with schizophrenia ⁽²³⁾. 

In young adults at risk for psychotic conditions, supplementation reduced the risk of progression to psychiatric disorders and was a safe preventive measure in young adults ⁽³⁵⁾ although conflicting data show no benefit against major depressive disorder ⁽⁸⁴⁾.

Supplementation in pregnant women did not lower the incidence of early preterm delivery, nor the higher incidence of interventions in post-term deliveries ⁽⁶⁷⁾, and did not improve cognitive or language outcomes in early childhood  ⁽³⁷⁾, or intelligence ⁽⁴²⁾. But DHA was shown to improve learning and memory function in age-related cognitive decline ⁽⁴¹⁾ although a large, long-term study of omega-3 with or without multidomain lifestyle interventions of physical activity, cognitive training, and nutritional advice failed to find significant effects on cognitive decline in elderly adults with memory complaints ⁽⁵²⁾.
Studies are mixed on the effects of supplementation on incidence or progression of age-related macular degeneration ^(73) (85).

Omega-3 lowers cholesterol ^(8) (33) and may reduce recurrence in patients with a history of stroke ⁽³²⁾. In individuals with cardiovascular risk factors, supplementation improved cardiometabolic profiles ⁽⁵³⁾, but did not prevent incident atrial fibrillation ⁽⁷⁸⁾ nor lower the risk of cardiovascular disease events ^(9) (72) although a meta analysis reported that protective effects of EPA and DHA increase with dosage ⁽⁷⁹⁾. Omega-3 may also help patients with ulcerative colitis ⁽¹⁰⁾, but was ineffective in the treatment of Crohn’s disease ⁽¹³⁾. In adults with rheumatoid arthritis, supplementation led to reductions in NSAID use ⁽¹⁴⁾ and in NSAID-associated gastroduodenal damage ⁽⁴⁷⁾. It may also lower the magnitude of the body’s inflammatory response ⁽¹⁸⁾, and can reduce sensitivity to sunburn ⁽²⁰⁾ and to ultraviolet radiation ⁽⁴⁴⁾. Reviews indicate possible benefits for patients with cystic fibrosis ⁽²¹⁾, but not in those with asthma ⁽²²⁾. 

Fish oil may help reduce the symptoms of systemic lupus erythematosus ⁽²⁴⁾. Another large trial also reported benefit, with or without vitamin D, in reducing the risk of autoimmune disease ⁽⁸⁰⁾.

In type 1 diabetic patients, long-term supplementation had positive effects on neuropathy, measured by increases in corneal nerve fiber length ⁽⁵⁴⁾. But there was no significant benefit in patients with dry eye disease ⁽⁶⁰⁾. A systematic review determined benefits of omega-3 on insulin sensitivity and adipocyte function ⁽⁴⁵⁾. However, high-dose supplementation did not improve features associated with metabolic syndrome such as adipose tissue lipolysis or inflammation in insulin-resistant adults ⁽⁵⁵⁾. In another trial, DHA was found more effective compared to eicosapentanoic acid (EPA) in modulating indicators of inflammation and blood lipids ⁽⁵⁰⁾. In women with gestational diabetes, omega-3 and vitamin E improved some markers of inflammation and oxidative stress as well as incidence of newborn hyperbilirubinemia ⁽⁵⁶⁾. In hemodialysis patients, omega-3 significantly reduced serum creatinine ⁽⁵⁷⁾, but did not reduce arteriovenous fistula failure ⁽⁵⁸⁾.

Data on omega-3 for cancer prevention are inconclusive. It may reduce colon cancer risk ⁽¹¹⁾; improve immune response in patients undergoing colorectal cancer resection ⁽¹²⁾; and reduce the incidence and severity of oxaliplatin-related neurotoxicity ⁽⁷⁴⁾ but did not affect cancer outcomes ^(15) (43). Also, perioperative use of intravenous omega-3 resulted in infectious complications in patients undergoing elective colon resection for non-metastasized cancer ⁽⁶⁸⁾. Conflicting data suggest beneficial association between higher omega-3 intake and improved survival among stage III colon cancer patients with wild-type KRAS and deficient MMR ⁽⁶⁹⁾; supplementation also reduced occurrence of renal cell carcinoma in women ⁽¹⁶⁾. Furthermore, fish oil may lower the risk of breast cancer ⁽³⁶⁾; improve overall survival ⁽⁷⁰⁾ and xerostomia, but not toxicity ⁽⁷¹⁾ associated with neoadjuvant chemotherapy in patients with locally advanced breast cancer. Data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed high blood levels of omega-3 to be associated with increased risk of prostate cancer ⁽¹⁷⁾. In patients with sporadic colorectal neoplasia, EPA did not affect reductions in the proportion of patients with at least one colorectal adenoma when compared to aspirin or placebo ⁽⁶¹⁾. Also, in the prevention trial VITAL, supplementation did not lower incidence of invasive cancer or major cardiovascular events compared to placebo ⁽⁶²⁾ although updated analyses show significant reduction in cancer mortality ⁽⁷⁵⁾.

Preliminary findings suggest that fish oil increases efficacy of chemotherapy, improves survival ⁽³⁸⁾, and helps maintain weight and muscle mass ⁽³⁹⁾ in patients with non-small cell lung cancer (NSCLC); and improves quality of life scores in gastrointestinal cancer patients  ⁽⁸¹⁾. But conflicting data suggest otherwise ^{(59)  (82)} although a positive correlation was reported between adherence to supplementation and the ability to reduce weight loss during radiotherapy ⁽⁸³⁾. Additional studies found an EPA-enriched oral supplement improved tolerability of chemotherapy in advanced colorectal cancer patients ⁽⁴⁰⁾; and when combined with chemotherapy, fish oil supplements may delay tumor progression in those with colorectal cancer ⁽⁴⁹⁾. Omega-3 may also have a protective effect on the olfactory system in patients following endoscopic resection of sellar and parasellar masses ⁽⁷⁶⁾.