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⁾. But treatment with omega-e redcued neuronal integrity breakdown in apolipoprotein E ε4 allele APOE*E4 carriers ⁽⁸⁸⁾.

A meta-analysis reported benefits of high dose EPA/DHA supplementation for migraine prophylaxis ⁽⁸⁹⁾. Omega-3 may also be useful in treating acne  ⁽⁹⁰⁾, but did not reduce symptoms of dry eye disease associated with meibomian gland dysfunction  ⁽⁹¹⁾, and 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⁾. However, regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but beneficial for progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death ⁽⁸⁷⁾. 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). Data are mixed on the benefits of perioperative use of omega-3 in reducing infectious complications ^(68) (92). 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 associated with neoadjuvant chemotherapy in patients with locally advanced breast cancer ⁽⁷¹⁾ or acute pain syndrome ⁽⁹³⁾. 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⁾.