IngredientsMarine fat — also termed marine oil, marine lipid, or marine omega-3 fat — is the collective designation for the lipid fraction extracted from marine organisms and distinguished by its high content of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs). Omega-3 (n-3) fatty acids are a family of polyunsaturated fatty acids characterized by the presence of the closest double bond to the methyl end of the hydrocarbon chain being on carbon number three, if the methyl carbon is counted as one.
Principal active fatty acids:
Natural Sources: The best dietary source of EPA and DHA (and also DPA) is seafood, especially fatty fish (also called "oily fish"). The blubber and tissues of sea mammals such as whales and seals also contain EPA and DHA in significant amounts. Various supplements, including fish oils, cod liver oil, krill oil, and some algal oils, contain EPA and DHA.
Specific species sources: EPA and DHA are found in seafood, especially cold-water fish such as salmon, mackerel, and tuna, as well as shellfish and fish oil supplements. Fatty fish such as herring, mackerel, tuna, salmon, and trout are rich dietary sources of EPA and DHA.
Algal origin: DHA and EPA are two types of n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) that are ubiquitous in marine animals and plant plankton. Microalgae represent the primary producers of EPA and DHA in the marine food chain, and algal oils are now used as a plant-derived source of these fatty acids, particularly in vegetarian and vegan formulations.
Marine fat is commercially available in several molecular and physical forms:
Molecular composition of supplements: Investigations of 46 commercially available marine oil omega-3 supplements identified 73 fatty acid isomers, including n-6, n-4, n-3, and n-1 polyunsaturated fatty acids and trans isomers of EPA (C20:5n-3) and DHA (C22:6n-3).
Oxidative stability: Oils and aqueous compositions containing long-chain polyunsaturated fatty acids (PUFA) are susceptible to oxidation, making them unstable and giving them an unpleasant taste.
The use of cod liver oil as a food dates back to the Viking Era (late 700s to 1100). Fish and fish liver oil were important parts of the Norse diet. The Vikings consumed most of the fish liver oil during the cold months when the days were shorter and lacked sunlight, coinciding with the prime fishing season when livers stayed fresh.
The most common method of obtaining fish liver oil used by the Scandinavian Vikings in Northern Norway involved bringing water in a large pan to a boil, placing birch tree branches on top, and laying the liver on the branches. As steam rose and cooked the liver, oil would drip into the water, and the straw-colored oil was skimmed off.
Dating back to distant antiquity, fat from the livers of cod and other fish species was used for illumination and heating. Both the Sámi people and the Inuit used fish and seal oil for light and warmth, and from the Middle Ages the oil became commonly used as lamp oil by other Europeans. Various findings from the years 230–895 in Northern Norway suggest that fish, seal, and whale oil were not only produced for local use but also used as trade and barter commodities.
In the 1750s, Erik Pontoppidan, a professor and bishop, highlighted the health-promoting effects of cod liver oil for both external and internal use. Cod liver oil had long been a "folk remedy" for various ailments. The earliest documented use of cod liver oil for medicinal purposes dates back to 1789 when a doctor in Manchester used cod liver oil as a remedy for rheumatism. It was also suggested by doctors in 1824 as a treatment for rickets, a deficiency disease caused by a lack of vitamin D.
A revolutionary innovation within cod liver oil production occurred in 1852 when Peter Möller introduced his new method of gentle steam extraction to make cod liver oil for medical purposes. Fresh cod liver was revered for medicinal purposes long before Peter Möller invented a modern method to extract its health-giving oil, and the product was considered a delicacy in Scotland and Norway for centuries.
The pivotal scientific turning point in the modern history of marine fat came in the 1970s. Danish doctor Jørn Dyerberg made the connection between the diet of Greenland Inuit — based on cold-water oily fish — and their low incidence of coronary disease. His work led to further studies on the health benefits of omega-3 fatty acids, paving the way for the innumerable fish-oil supplements available today. Researchers published a landmark paper in The Lancet on July 15, 1978 entitled "Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis?" presenting data supporting the idea that EPA (from seafoods consumed by the Inuit) could substitute for arachidonic acid in the cyclo-oxygenase pathway.
EPA and DHA are able to inhibit partly a number of aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid, production of inflammatory cytokines, and T cell reactivity. In parallel, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid, and EPA and DHA give rise to anti-inflammatory and inflammation-resolving resolvins and protectins.
Marine oils are considered vital for brain health because 20% of the brain's dry weight comprises polyunsaturated fatty acids as a major structural component of neuronal cell membrane phospholipids. The omega-3 fatty acids are essential to life at any stage. They are essential building blocks of the membrane of every cell in the body, and are also used in the regulation of most biological functions, including those of the cardiovascular, reproductive, immune, and nervous systems.
Resolvins are thought to be the active metabolites of omega-3 PUFA and are responsible for facilitating the resolving phase of acute inflammation. Clinically, resolvins have been associated with resolution of acute kidney injury and acute lung injury, as well as micro- and macrovascular response to injury. Resolvin D1 and Protectin D1 are potent, endogenous, DHA-derived lipid mediators that attenuate neutrophil migration and tissue injury in peritonitis and ischemia-reperfusion injury.
In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid, and EPA and DHA give rise to anti-inflammatory and inflammation-resolving mediators called resolvins, protectins, and maresins.
Natural fish oils and cod liver oil contain fat-soluble vitamins A and D, as well as minor quantities of other fatty acid classes. Among the 73 fatty acid isomers detected in commercial marine oil supplements are n-6, n-4, n-3, and n-1 polyunsaturated fatty acids.
EPA and DHA are able to inhibit many aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from arachidonic acid, production of inflammatory cytokines, and T cell reactivity. In parallel, EPA gives rise to eicosanoids that often have lower biological potency and EPA and DHA give rise to anti-inflammatory and inflammation-resolving resolvins and protectins. At a sufficiently high dose, marine n-3 PUFAs exert a range of anti-inflammatory actions, resulting in decreased production of classic inflammatory cytokines TNF, IL-1β, and IL-6, and decreased T-cell reactivity. Overall, these observations indicate a shift from a strongly pro-inflammatory environment to one of reduced inflammation and increased resolution.
Mechanisms underlying the anti-inflammatory actions of n-3 fatty acids include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB), thereby reducing expression of inflammatory genes, and activation of the anti-inflammatory transcription factor NR1C3.
Proposed mechanisms of action of omega-3 fatty acids in triglyceride reduction include inhibition of diacylglycerol acyltransferase, increased plasma lipoprotein lipase activity, decreased hepatic lipogenesis, and increased hepatic β-oxidation.
Marine fish oil rich in long-chain omega-3 PUFAs plays an important role in reducing abnormalities associated with the metabolic syndrome and has a variety of disease-fighting properties, including cardioprotective activity, anti-atherosclerotic, anti-obesity, anti-cancer, and anti-inflammatory activity. The incorporation of EPA and DHA into cell membrane phospholipids alters membrane fluidity, receptor function, and downstream signaling cascades.
Basic research has shown that omega-3 increases brain-derived neurotrophic factor (BDNF) levels in brain regions associated with depression, as antidepressant drugs do. Omega-3 fatty acids are involved in a wide range of physiological functions related to neurogenesis, neurotransmission, and neuroinflammation; therefore, they play fundamental roles in the development, functioning, and aging of the brain.
The triglyceride-lowering effect of marine fat is the most robustly established clinical action. The strongest effect of marine oils is on triglyceride concentrations. Across studies, this effect was dose-dependent and related to studies' mean baseline triglyceride concentration.
A dose-response clinical trial compared 0.85 g/day with 3.4 g/day of EPA+DHA in a placebo-controlled, double-blind, randomized, 3-period crossover design in 26 adults with moderate hypertriglyceridemia. The higher dose of EPA+DHA lowered triglycerides by 27% compared with placebo (mean ± SEM: 173 ± 17.5 vs. 237 ± 17.5 mg/dL; P = 0.002). However, the higher dose (3.4 g/d) significantly lowered triglycerides, but neither dose improved endothelial function or inflammatory status over 8 weeks in healthy adults with moderate hypertriglyceridemia.
A review of 38 clinical intervention studies assessing 2,270 individuals found that a 9–26% reduction in circulating TG was demonstrated in studies where ≥4 g/day of n-3 PUFA were consumed from marine or EPA/DHA-enriched food sources, while a 4–51% reduction was found in studies where 1–5 g/day of EPA and/or DHA was consumed through supplements.
Lovaza is indicated as an adjunct to diet to reduce triglyceride levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. Evidence strength: High. Multiple RCTs and meta-analyses with consistent dose-dependent effects; FDA-approved indication at 4 g/day for severe hypertriglyceridemia.
The evidence for marine fat supplementation reducing major cardiovascular events (MACE) is mixed and depends substantially on dose, formulation, and patient population.
VITAL Trial: The NIH-funded VITAL study enrolled nearly 26,000 U.S. adults aged 50 and older without a history of heart disease, stroke, or cancer and followed them for five years. The primary findings showed that taking 1 gram of omega-3 supplements daily did not significantly lower the overall risk of major cardiovascular disease events. However, in the VITAL trial, 840 mg/d of EPA and DHA resulted in a 28% reduced risk for heart attacks, 50% reduced risk for fatal heart attacks, and 17% reduced risk for total coronary heart disease events. In the ASCEND trial, cardiovascular disease death was significantly reduced by 19% with 840 mg/d of EPA and DHA. However, the primary composite end points were not significantly reduced in either study.
REDUCE-IT Trial: The REDUCE-IT reported a decrease of 25% in major cardiovascular events with the use of 4 g of icosapent ethyl over a median follow-up of 4.9 years. The REDUCE-IT trial was conducted among 8,179 statin-treated patients with CVD or diabetes and with high triglycerides.
Atherosclerosis: A systematic review and meta-analysis of 6 RCTs found that high-dose omega-3 significantly slowed the progression of atherosclerosis (standardized mean difference −1.97, 95% CI −3.01 to −0.94, P <0.001). The results indicate that the anti-atherosclerotic effect of high-dose omega-3 is one potential mechanism in reducing CVD outcomes demonstrated in the REDUCE-IT trial.
Meta-Analysis of 13 RCTs: An updated meta-analysis incorporating data from 13 RCTs, including 3 recent large trials, suggests that marine omega-3 supplementation is associated with lower risk of MI, total CHD, total CVD, and death from CHD or CVD causes. Such inverse associations may be particularly evident at higher doses.
Evidence strength: Moderate-to-strong for benefit at higher doses (≥3–4 g/day) in high-risk populations; weak-to-moderate at lower doses for primary prevention. Overall evidence is inconsistent across trials.
A systematic review and meta-analysis covering over 81,210 participants across multiple large RCTs found that the pooled hazard ratio for the association between marine omega-3 fatty acids and atrial fibrillation (AF) was 1.25 (95% CI 1.07–1.46, P=0.013). This signals a potential increased risk of AF with marine omega-3 supplementation, particularly at higher doses. Recurrent atrial fibrillation or flutter was observed when an initial high dose of Lovaza was administered (i.e., 8 g/day for 1 week, then 4 g/day thereafter).
Evidence strength: Moderate signal of increased AF risk, especially at high doses. This is a recognized safety concern supported by multiple large RCTs.
In humans, dietary deficiencies of omega-3 fatty acids are associated with an increased risk of developing various psychiatric disorders, including depression, bipolar disorder, schizophrenia, dementia, attention-deficit/hyperactivity disorder, and autism.
Case-control studies have consistently observed low erythrocyte EPA and/or DHA levels in patients with major depressive disorder, bipolar disorder, schizophrenia, and attention deficit hyperactivity disorder. Low erythrocyte EPA+DHA status can be treated with fish oil-based formulations containing preformed EPA+DHA, and extant evidence suggests that fish oil supplementation is safe and well-tolerated and may have therapeutic benefits.
The findings of open-label and controlled studies lend support to the beneficial effects of omega-3 fatty acids on depressive symptoms and, to a lesser degree, manic symptoms. Omega-3 PUFAs administered as an add-on to standard pharmacotherapy have been found to improve both depression and mania scores. Other studies have found that omega-3 PUFAs have no effects on bipolar disorder.
While far from robust, there is enough epidemiological, laboratory, and clinical evidence to suggest that omega-3 fatty acids may play a role in certain cases of depression. However, the routine use of omega-3 fatty acids for the treatment of major depressive disorder (MDD) cannot be recommended. The data are far from unequivocal, and large trials are warranted to truly determine efficacy, appropriate dosing, and the potentially active components — EPA, DHA, or both.
Evidence strength: Preliminary to moderate; consistent association data but RCT results are mixed. EPA appears more relevant than DHA for mood disorders.
EPA has been found to reduce positive, negative, depressive, and anxious symptoms associated with schizophrenia and may reduce violent behaviors as well. Medium- and long-term efficacy of omega-3 fatty acids in stable schizophrenia is not known.
Two separate clinical trials on Alzheimer's patients and Parkinson's patients supplemented with n-3 PUFA enriched diets failed to deliver a robust outcome. The trials found n-3 PUFA effective only if administered during the early onset of Alzheimer's disease; in treating Parkinson's disease, its efficacy was restricted to mitigating depression syndromes only.
Evidence strength: Preliminary. Promising signals in early-stage cognitive decline and certain psychiatric conditions, but clinical trial results are inconsistent and often inconclusive.
Recent research has shown that marine fish oil (found in tuna, sardines, and mackerel) may offer an alternative method for reducing obesity. Marine fish oil rich in long-chain omega-3 PUFAs plays an important role in reducing abnormalities associated with the metabolic syndrome and has a variety of disease-fighting properties, including cardioprotective, anti-atherosclerotic, anti-obesity, and anti-inflammatory activity.
Studies in rodents and humans have indicated that LC n-3 PUFA potentially elicit a number of effects which might be useful for reducing obesity, including suppression of appetite, improvements in circulation, enhanced fat oxidation, energy expenditure, and reduced fat deposition.
Evidence strength: Modest in humans. Animal studies show consistent effects; human trial data are less definitive and preliminary.
Based on numerous trials, there is high strength of evidence of no significant effects of marine oils on systolic or diastolic blood pressures, but there are small yet statistically significant increases in high-density lipoprotein and low-density lipoprotein cholesterol concentrations.
Evidence strength: High — no meaningful blood pressure-lowering effect from marine fat supplementation alone has been established in clinical trials.
EPA and DHA exhibit anti-inflammatory effects by promoting the production of specialized pro-resolving mediators (SPMs) such as resolvins and protectins. Fish oil has been studied for its potential to reduce bronchial inflammation, a key feature of respiratory conditions like asthma and COPD. The beneficial effects of omega-3 fatty acids have been demonstrated in several studies in the context of lung diseases; dietary fish oil has been shown to alleviate symptoms and improve lung function in models of COPD, asthma, and acute respiratory distress syndrome (ARDS).
Evidence strength: Largely preclinical and early clinical. Robust human RCT data in respiratory disease are limited.
An overview of major animal studies and clinical trials focuses on fatty acid supplementation during pregnancy and infancy, and prevention and management of Alzheimer's disease, schizophrenia, depression, and attention deficit hyperactive disorder. Although an optimal balance in n-3/n-6 long-chain PUFA ratio is important for proper neurodevelopment and cognitive functions, results from randomized controlled trials are controversial and do not confirm any useful effect of supplementation on development in all studies.
Evidence strength: Mixed. Observational evidence supports a role for DHA in fetal neurodevelopment; clinical RCTs on cognitive outcomes are inconsistent.
Dietary reference values: There is no established Dietary Reference Intake for n-3 fatty acids, yet the Adequate Intake (AI) is set at 1.6 and 1.1 grams/day for men and women, respectively. While intake in the United States occurs at much lower than the proposed AI, the AI is proposed to provide optimal health benefits associated with consuming n-3 fatty acids.
FDA Generally Recognized as Safe (GRAS): The FDA has ruled that intakes of up to 3 g/d of marine n-3 fatty acids are generally recognized as safe (GRAS) for inclusion in the diet.
AHA recommendations: Two to three servings of fish per week provide approximately 250–300 mg/day of EPA and DHA. For patients with coronary heart disease, the AHA recommends 1,000 mg/day of EPA and DHA.
Doses used in specific studies and contexts:
The molecular form in which EPA and DHA are delivered significantly influences bioavailability. Fish oils contain EPA and DHA predominantly bound in triglycerides. The difference in the chemical binding of EPA and DHA has been suggested to affect their bioavailability.
A network meta-analysis of 26 high-quality studies found superior bioavailability of krill oil compared to fish oil. Krill oil phospholipid/free fatty acid forms have the highest area-under-the-curve (AUC) values. However, other research presents a more nuanced picture: EPA and DHA in krill oil had a higher 72-hour bioavailability than in krill meal or fish oil, but the finding that bioavailabilities of EPA and DHA in krill meal and fish oil were not different argues against the interpretation that phospholipids are always better absorbed than triglycerides.
The bioavailability (area under the plasma concentration-time curve) of omega-3 carboxylic acids (OM3CA) is up to 4-fold greater than that of omega-3 fatty acid ethyl esters, and unlike ethyl esters, the absorption of OM3CA is not dependent on pancreatic lipase hydrolysis.
All three major marine omega-3 formulations (ethyl esters, triglycerides, carboxylic acids) are well tolerated, with the most common adverse events being gastrointestinal, and demonstrate a lack of drug-drug interactions with other lipid-lowering drugs such as statins and fibrates.
Detrimental effects of excess intake of n-3 fatty acids in healthy populations include depression of the immune function, bleeding, and increased risk of hemorrhagic stroke, as well as increased lipid peroxidation resulting in oxidative damage to various tissues. Marine omega-3 fatty acids may prolong bleeding time (use caution). Patients taking omega-3 fatty acids and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.
Marine omega-3 fatty acids may cause an increase in the frequency of atrial fibrillation or flutter, especially in the first few months of taking them, particularly in individuals who already have a heart rhythm problem.
Marine omega-3 fatty acids may increase liver ALT without increasing AST (monitoring is recommended). They may also increase LDL levels (monitoring is recommended).
It has been suggested that diabetics or individuals with impaired glucose tolerance should use n-3 fatty acid supplements with caution, since they might have detrimental effects on glucose homeostasis. Increased incidences of nosebleeds have also been reported in individuals with hypercholesterolemia with n-3 fatty acid supplementation.
It is not known whether omega-3-acid ethyl esters are excreted in human milk. Safety and effectiveness in pediatric patients have not been established.
Caution is warranted in patients allergic to fish.
Lovaza (omega-3-acid ethyl esters) may interact with birth control pills or hormone replacement, blood thinners, beta-blockers, or diuretics (water pills).
Fish oil used in the manufacture of Lovaza undergoes an intense purification process that includes removal of pesticides, cholesterol, fatty acids, and by-products. Most dietary supplements of fish oils do not undergo as rigorous a purification process and have a "fishier" taste. Contents of EPA and DHA met their respective label declarations in more than 80% of commercial products examined, indicating that product quality is generally consistent but not universal.
Health conditions that Marine fat may help support.
Body systems that Marine fat may help support.
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