Fish Oil

Fish oil and cardiovascular disease: lipids and arterial function


n−3 Fatty acids have been shown to modify several key risk factors for cardiovascular disease. However, it is not clear whether the apparent protection against cardiovascular disease is directly related to antiatherogenic functions of these fatty acids or is mediated through their modification of the risk factors through mechanisms not directly related to lipids. A major question concerns the importance of lipid modification, which is a potent outcome of fish-oil supplementation. On balance, lipid modification is likely to represent a significant antiatherogenic factor. The benefits include increased HDL 2 -cholesterol concentrations, reduced triacylglycerol-rich lipoprotein concentrations, reduced postprandial lipemia, and reduced remnant concentrations. In contrast, LDL-cholesterol concentrations have often been noted to rise and the potential of increased oxidizability of LDLs is potentially adverse with lipid modification, but this potential can be overcome with vitamin E supplementation. The characteristic lipid changes and the underlying mechanisms are reviewed. Additional benefits of fish oils include improved endothelial function and better arterial compliance (elasticity). Future trials will be needed to determine minimum effective dosages of eicosapentaenoic and docosahexaenoic acids over lengthy periods and to show cardiovascular disease reduction through intervention.


The active molecules of fish-oil n–3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and possibly other minor fatty acids, are multipotent compounds. Throughout 20 y of research, their potential to counter atherosclerotic vascular diseases has been supported by an increasingly lengthy list of functions, some related to lipid metabolism but others mediated through nonlipid mechanisms. On the negative side, there may be one or more adverse effects of n−3 fatty acids. On balance, if n−3 fatty acids are to be the major explanation for the protection afforded by eating fish, it will be necessary to resolve some key issues. 1) Which of the effects of EPA, DHA, or both best explain the presumptive protective effects? 2) Are the changes in lipid metabolism sufficient to provide protection, given that the amounts of n−3 fatty acids needed to show beneficial effects on lipids are far greater than are consumed by fish eaters (other than in unusual populations)? 3) Could small amounts of n−3 fatty acids be adequate nevertheless if eaten over long periods of time? These issues are shown in Table 1.

TABLE 1 1) If fish oil inhibits atherosclerosis, how much of this effect is attributable to lipoprotein changes? 2) Is lowering triacylglycerol beneficial? 3) When and why is LDL cholesterol raised and is this necessarily adverse? 4) Is lipoprotein oxidation a threat? 5) Are there benefits secondary to lipid lowering? 6) Given that the above effects require fish oil in amounts exceeding those derived from eating fish, what are the minimal protective amounts of n−3 fatty acids? 1) If fish oil inhibits atherosclerosis, how much of this effect is attributable to lipoprotein changes? 2) Is lowering triacylglycerol beneficial? 3) When and why is LDL cholesterol raised and is this necessarily adverse? 4) Is lipoprotein oxidation a threat? 5) Are there benefits secondary to lipid lowering? 6) Given that the above effects require fish oil in amounts exceeding those derived from eating fish, what are the minimal protective amounts of n−3 fatty acids? Open in new tab

TABLE 1 1) If fish oil inhibits atherosclerosis, how much of this effect is attributable to lipoprotein changes? 2) Is lowering triacylglycerol beneficial? 3) When and why is LDL cholesterol raised and is this necessarily adverse? 4) Is lipoprotein oxidation a threat? 5) Are there benefits secondary to lipid lowering? 6) Given that the above effects require fish oil in amounts exceeding those derived from eating fish, what are the minimal protective amounts of n−3 fatty acids? 1) If fish oil inhibits atherosclerosis, how much of this effect is attributable to lipoprotein changes? 2) Is lowering triacylglycerol beneficial? 3) When and why is LDL cholesterol raised and is this necessarily adverse? 4) Is lipoprotein oxidation a threat? 5) Are there benefits secondary to lipid lowering? 6) Given that the above effects require fish oil in amounts exceeding those derived from eating fish, what are the minimal protective amounts of n−3 fatty acids? Open in new tab


Triacylglycerol-rich lipoproteins

The concentrations of endogenously derived triacylglycerol-rich lipoproteins, VLDLs, and intermediate-density lipoproteins have been almost uniformly reported to be lowered with fish oil. Fish oils have been effective in normal subjects and in patients with common phenotypes of hyperlipidemia in which VLDL concentrations are raised. The minimum effective dose of n−3 fatty acids appears to be slightly more than 1 g/d. At intakes >2 g/d, VLDLs decreased an average of 25% in normal subjects and even more in hypertriglyceridemic subjects (≈50% in those with the type 4 or 5 phenotype and ≈40% in those with combined hyperlipoproteinemia) (1). Furthermore, this response is maintained. What of chylomicrons and chylomicron remnants? In more severe forms of hypertriglyceridemia, such as type 5 hyperlipoproteinemia, in which both VLDLs and chylomicrons (or remnants) are present, excess n−3 fatty acids can be highly effective. Whether this result reflects enhanced removal of chylomicrons is uncertain. Catabolized VLDLs and chylomicrons compete for similar removal mechanisms; diminished chylomicron removal may therefore occur whenever VLDL overproduction increases the need for VLDL removal, as in type 5 hyperlipoproteinemia. Chylomicronemia after a fatty meal is diminished when fish oil is eaten over 2 wk (2) but not after a single meal. Remnants in type 3 hyperlipoproteinemia are partly cleared with fish-oil treatment (3).

Dietary fish oils also modify the type of hypertriglyceridemia that is normally inducible by carbohydrates (4). This modification might be expected from the known effects of these 2 nutrients on triacylglycerols: carbohydrates stimulate and fish oils inhibit VLDL production. This is seen strikingly in hepatocytes from obese hyperlipidemic rats in which the usual overproduction of lipid is suppressed with DHA (5).

The nature of the predominant n−3 fatty acids (EPA and DHA) does not seem important in determining plasma triacylglycerol lowering in humans. Fish or fish oils rich in EPA appear to be as effective in humans as is fish rich in DHA. Fish oils vary considerably in their content of EPA and DHA as well as that of long-chain monoenes and docosapentaenoic acid. A dose-response trial comparing EPA and DHA is urgently needed.

Much larger amounts of fish oil than of individual n−3 fatty acids must be taken to produce an effect. However, whole fish oils are rich in saturated fatty acids that may be undesirable. Therefore, esters of individual n−3 fatty acids have been used. The absorption of the ethyl or methyl esters of EPA appears to be inferior to that of EPA in the glycerides of the fish oils, yet the esters have been therapeutically effective in dosages roughly equal to those in fish oil.

In summary, fish oils affect VLDL metabolism by 1) reducing VLDL triacylglycerol secretion, as clearly shown in kinetic studies in humans, animal liver perfusions, and isolated hepatocytes (6); 2) generally, but not always, increasing VLDL apoliprotein B secretion (6, 7) [at least in rat liver, this may be related to increased apolipoprotein B degradation (8), thus assembly of VLDL is impaired]; 3) reducing triacylglycerol transport, resulting in smaller VLDLs, which are largely converted to LDLs; and 4) less certainly, increasing VLDL clearance. The key enzyme lipoprotein lipase has mostly been found to be unaffected by fish oil in humans (9).

Chylomicron metabolism

Although there is agreement that chylomicron assembly and secretion are reduced in isolated intestinal cells incubated with EPA, the interpretations of results differ. The mechanisms appear to include the reduction of apolipoprotion B formation and the diversion of EPA from triacylglycerols to phospholipids (10).

Hepatic triacylglycerol metabolism

Reduced triacylglycerol formation is ascribed largely to reduced fatty acid availability. Studies have confirmed that 1) fish oil increases oxidation of fatty acids by peroxisomal as well as mitochondrial routes (11), which may be mediated by peroxisome proliferator in the liver (12); 2) fish oil reduces fatty acid synthesis (owing to suppression of key enzymes); 3) fish oil diverts fatty acids to phospholipids (6); 4) although fish oil reduces plasma fatty acids, this may be due to increased hepatic uptake through a transporter protein (12); 5) within the liver, triacylglycerol assembly is impaired through down-regulation of esterifying enzymes (13).

Cholesterol metabolism

Fish oil reduces cholesterol absorption in humans (6) and in monkeys (14). Cholesterol synthesis in the liver is reduced and cholesterol secretion within VLDLs is lowered (6).

LDL metabolism and oxidation

The effects of fish oil on LDL metabolism represent the more controversial aspects of the n−3 fatty acid effects. Why does fish oil cause LDL-cholesterol concentrations to sometimes rise, at least in humans, when all the evidence suggests it should not? Fish oil depresses cholesterol synthesis and may reduce cholesterol absorption (6). This focuses attention on LDL removal and particularly on the LDL (apolipoprotein B/E) receptor. There is evidence that fish oil down-regulates the receptor in hepatic cells (15, 16). Abnormal LDL binding to the receptor in human monocytes (16) and to skin fibroblasts has been ascribed to abnormalities in the LDL itself (17).

Changes in the LDL particles are minor, but tend toward larger, cholesterol-enriched LDLs (18, 19). LDL size relates to the exchange of lipids between LDL, VLDL, and HDL. Fish oil would reduce such exchanges through suppression of cholesterol ester transfer protein and thus favor larger LDL particles (18). Reduced LDL synthesis has been reported with large amounts of fish oil (20).

The n−3 enrichment renders LDLs susceptible to oxidation, as has been shown in several reported studies, with some exceptions. The obvious relevance is to atherogenesis, which is favored by oxidized lipoproteins. The evidence includes increases in in vitro copper-oxidized and macrophage-modified changes in LDL that lead to their increased uptake by macrophages (19). These findings define a potential atherogenic property of dietary fish oil, although it must be emphasised that these are in vitro observations and that the sum of the metabolic outcomes of marine n−3 fatty acids appears to be antiatherogenic in life. Nevertheless, our findings indicate a need for increased antioxidant action, such as that provided by α-tocopherol, if large amounts of fish oil are to be consumed. We have in fact shown that, at least in vitro, the addition of vitamins E and C to n−3 fatty acid–enriched macrophages inhibits their capacity to oxidize LDLs (21). In a study in pigs fed atherogenic diets, however, atherosclerosis was not increased in animals fed fish oil, despite evidence of raised in vitro LDL oxidizability (22).

HDL metabolism

Most reports indicate a favorable effect of fish oil on HDLs. The number of larger cholesterol-rich HDLs (in the HDL 2 range) increases at the expense of HDL 3 (18). However, very high intake of fish oil may lower HDL concentrations (6).

The major effect of fish oil on HDL metabolism is mediated by a reduction in activity of cholesterol ester transfer protein (18), which transfers cholesterol esters from HDLs to VLDLs and LDLs, largely in exchange for VLDL triacylglycerols. Because triacylglycerol concentrations are also reduced, exchange is further diminished, favoring large cholesterol-rich HDL (and LDL) particles over the formation of triacylglycerol-enriched HDLs (and LDLs), which are more susceptible to catabolism.


Data supporting a relation between fish oil and arterial disease are summarized in Figure 1 and only a few will be discussed further. Other aspects are discussed elsewhere in the supplement.

FIGURE 1. Open in new tabDownload slide Evidence of a relation between fish oil and arterial disease.

FIGURE 1. Open in new tabDownload slide Evidence of a relation between fish oil and arterial disease.

The reduction in triacylglycerols is one of the modifications in the risk profile. High triacylglycerol concentrations are now widely recognized as an independent risk factor for cardiovascular disease, although the coexistence of low HDL or high LDL concentrations augments the risk substantially. The atherogenicity of intermediate-density lipoproteins, the remnant of VLDL catabolism, is being rediscovered (23).

Modification of dyslipidemia has been the most characteristic effect of fish oils. Triacylglycerol-rich lipoproteins are almost invariably reduced by mechanisms that are now mostly understood. Postprandial lipemia is reduced (9) and potentially atherogenic remnants are cleared. This facilitation of triacylglycerol catabolism partly explains the desirable rise in HDL 2 -cholesterol concentrations.

The myocardium is certainly protected from the full damage of ischemia in animals fed fish oil, in which the infarct size is smaller, blood flow is better maintained, and several metabolic disturbances (eg, oxidative damage and calcium overload) that can induce arrhythmias are modified. The protection by fish oils of the myocardium, together with reduction of risk factors and the beneficial modification of arterial responses, explain much of the favorable effectiveness of fish oils (24).

Endothelium-dependent dilatation of arteries is enhanced by fish oils, which also inhibit the vasoconstrictive effects of sympathetic overactivity and norepinephrine (25). We showed that the vascular resistance in the microcirculation of the forearm (which mimics that in the coronary circulation) that occurs when norepinephrine or angiotensin II are infused is attenuated by taking fish oil (25). The improvement might have been due in part to the better lipid profile, because dyslipidemia impairs endothelial function. (Blood pressure was not altered in this study, although this risk factor is reducible in hypertensive subjects.) Endothelial dysfunction is now a well-recognized cause of clinical symptoms in cardiovascular disease and its reversal improves prognosis.

Another index of arterial function is compliance, a measure of the elasticity of large arteries, including the thoracic aorta. Compliance has been reported to be improved by treating diabetic patients (in whom compliance is low as arteries stiffen), with fish oil (26). Of importance is that this improvement in function is achieved within a few weeks.


The underlying support for fish oil in the management of cardiovascular risk is the apparent protection that eating fish provides. Several large studies have documented such protection from relatively small amounts of fish eaten regularly (27–29). However, this was not observed in a large US study, the Health Professionals Follow-up Study, published in 1995 (30). The most plausible explanation for this exceptional finding is that the average consumption of fish (or fish oil) was already high in these individuals, reducing the likelihood of showing a dose-related response. The current consensus is that eating fish is beneficial at surprisingly modest intakes, and the benefit probably depends on the fatty acid profile of the fish consumed.

We reported that when equivalent amounts of n−3 fatty acids (4 g/d) are eaten as fish or as fish oil, the risk reduction may be greater with fish (31). A recent report of Tanzanian villagers showed that eating fish (3–5 g n−3 fatty acids/d) outperformed vegetarianism in risk factor reduction (32).

Because fish oils will likely be prescribed for patients with or at risk of clinical cardiovascular disease, at issue is whether this will be in the form of the whole fish oils or more purified fatty acids. This will depend on results of future research on whether EPA, DHA, or both in conjunction have superior therapeutic characteristics.


1 Harris WS . Fish oils and plasma lipid and lipoprotein metabolism in humans . J Lipid Res 1989 ; 30 : 785 – 807 . 2 Weintraub MS , Zechner R , Brown A , Eisenberg S , Breslow JL . Dietary polyunsaturated fats of the omega-6 and omega-3 series reduce postprandial lipoprotein levels . J Clin Invest 1988 ; 82 : 1884 – 93 . 3 Dallongeville J , Boulet L , Davignon J , Lussier-Cacan S . Fish oil supplementation reduces beta-very low density lipoprotein in type III dysbetalipoproteinemia . Arterioscler Thromb 1991 ; 11 : 864 – 71 . 4 Harris WS , Connor WE , Inkeles SB , Illingworth DR . Dietary omega-3 fatty acids prevent carbohydrate-induced hypertriglyceridemia . Metabolism 1984 ; 33 : 1016 – 9 . 5 Wong S , Reardon M , Nestel PJ . Reduced triglyceride formation from long-chain polyenoic fatty acids in rat hepatocytes . Metabolism 1985 ; 34 : 900 – 5 . 6 Nestel PJ . Effects of n−3 fatty acids on lipid metabolism . Annu Rev Nutr 1990 ; 10 : 149 – 67 . 7 Nestel PJ , Connor WE , Reardon MF , Connor S , Wong S , Boston R . Suppression by diets rich in fish oil of very low density lipoprotein production in man . J Clin Invest 1984 ; 74 : 82 – 9 . 8 Wang H , Chex X , Fisher EA . n−3 Fatty acids stimulate intracellular degradation of apoprotein B in rat hepatocytes . J Clin Invest 1993 ; 91 : 1380 – 9 . 9 Harris WS , Connor WE , Alam N , Illingworth DR . Reduction of postprandial triglyceridemia in humans by dietary n−3 fatty acids . J Lipid Res 1988 ; 29 : 1451 – 60 . 10 Murthy S , Albright E , Mathur SN , Field FJ . Modification of CaCo-2 cell membrane fatty acid composition by eicosapentaenoic acid and palmitic acid: effect on cholesterol metabolism . J Lipid Res 1988 ; 29 : 773 – 80 . 11 Rustan AC , Christiansen EN , Drevon CA . Serum lipids, hepatic glycerolipid metabolism and peroxisomal fatty acid oxidation in rats fed omega-6 and omega-3 fatty acids . Biochem J 1992 ; 283 : 333 – 8 . 12 Barrans A , Jaspard B , Barbaras R , Chap H , Perret B , Collet X . Pre-βHDL: structure and metabolism . Biochim Biophys Acta 1996 ; 1300 : 73 – 85 . 13 Marsh JB , Topping DL , Nestel PJ . Comparative effects of dietary fish oil and carbohydrate on plasma lipids and hepatic activities of phosphatidate phosphohydrolase, diacyglycerol acyltransferase and neutral lipase activities in the rat . Biochim Biophys Acta 1987 ; 922 : 239 – 43 . 14 Parks JS , Crouse JR . Reduction of cholesterol absorption by dietary oleinate and fish oil in African green monkeys . J Lipid Res 1992 ; 33 : 559 – 68 . 15 Roach PD , Kambouris AM , Trimble RP , Topping DL , Nestel PJ . The effects of dietary fish oil on hepatic high density and low density lipoprotein receptor activities in the rat . FEBS Lett 1987 ; 222 : 159 – 62 . 16 Lindsey S , Pronczuk A , Hayes KC . Low density lipoprotein from humans supplemented with n−3 fatty acids depresses both LDL receptor activity and LDLr mRNA abundance in HepG2 cells . J Lipid Res 1992 ; 33 : 647 – 58 . 17 Linga V , Leight MA , Curtiss LK , Marcel YL , Richard W , et al. Dietary fish oil-induced decrease in low density lipoprotein binding to fibroblasts is mediated by apolipoprotein E . J Lipid Res 1994 ; 35 : 491 – 500 . 18 Abbey M , Clifton P , Kestin M , Belling B , Nestel PJ . Effect of fish oil on lipoproteins, lecithin:cholesterol acyltransferase, and lipid transfer protein activity in humans . Arteriosclerosis 1990 ; 10 : 85 – 94 . 19 Suzukawa M , Abbey M , Howe PRC , Nestel PJ . Effects of fish oil fatty acids on low density lipoprotein size, oxidizability, and uptake by macrophages . J Lipid Res 1995 ; 36 : 437 – 84 . 20 Illingworth DR , Harris WS , Connor WE . Inhibition of low density lipoprotein synthesis by dietary omega-3 fatty acids in humans . Arteriosclerosis 1984 ; 4 : 270 – 5 . 21 Suzukawa M , Abbey M , Clifton P , Nestel PJ . Enhanced capacity of n−3 fatty acid–enriched macrophages to oxidize low density lipoprotein mechanisms and effects of antioxidant vitamins . Atherosclerosis 1996 ; 124 : 157 – 69 . 22 Whitman SC , Fish JR , Rand ML , Rogers KA . n−3 Fatty acid incorporation into LDL particles renders them more susceptible to oxidation in vitro but not necessarily more atherogenic in vivo . Arterioscler Thromb 1994 ; 14 : 1170 – 6 . 23 Nestel PJ . New lipoprotein profiles and coronary heart disease . Circulation 1990 ; 82 : 649 – 51 . 24 Nestel PJ . Fish oil and cardiac function . World Rev Nutr Diet 1991 ; 66 : 268 – 77 . 25 Chin JPF , Gust AP , Nestel PJ , Dart AM . Marine oils dose-dependently inhibit vasoconstriction of forearm resistance vessels in humans . Hypertension 1993 ; 21 : 22 – 8 . 26 McVeigh GE , Brennan GM , Cohn JN , et al. Fish oil improves arterial compliance in non-insulin-dependent diabetes mellitus . Arterioscler Thromb 1994 ; 14 : 1425 – 9 . 27 Kromhout D , Feskens EJ , Bowles CH . The protective effect of small amounts of fish on coronary heart disease mortality in an elderly population . Int J Epidemiol 1995 ; 24 : 340 – 5 . 28 Daviglus ML , Stamler J , Orencia AJ , et al. Fish consumption and the 30-year risk of fatal myocardial infarction . N Engl J Med 1997 ; 336 : 1046 – 53 . 29 Siscovick DS , Ragunathan TE , King I , et al. Dietary intake and cell membrane levels of long-chain n−3 polyunsaturated fatty acids and the risk of primary cardiac arrest . JAMA 1995 ; 274 : 1363 – 7 . 30 Ascherio A , Rimm EB , Stampfer MN . Dietary intake of marine n−3 fatty acids, fish intake, and the risk of coronary disease among men . N Engl J Med 1995 ; 332 : 977 – 82 . 31 Cobiac L , Clifton PM , Abbey M , Belling GB , Nestel PJ . Lipid, lipoprotein, and hemostatic effects of fish vs fish-oil n−3 fatty acids in mildly hyperlipidemic males . Am J Clin Nutr 1991 ; 53 : 1210 – 6 . 32 Pauletto P , Puato M , Caroli MG , Casiglia E , Munhambo AE . Blood pressure and atherogenic lipoprotein profiles of fish-diet and vegetarian villagers in Tanzania: the Lugalawa study . Lancet 1996 ; 348 : 784 – 8 .

© 2000 American Society for Clinical Nutrition

24 Benefits of Fish Oil (Omega-3) + Dosage & Safety

Modern Western diets are dramatically low in anti-inflammatory omega-3 fats, which contributes to heart disease, cancer, and other chronic conditions. Fish oil is an excellent source of omega-3s that can reduce inflammation and protect the heart, brain, bones, and more. Read on to learn the benefits, dosage, and safety of fish oil supplementation.

What is Fish Oil?

Fish oil is a great source of anti-inflammatory, omega-3 healthy fats. It contains two omega-3 fatty acids known as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Our bodies can produce them from an essential fatty acid, ALA, but the efficacy of this conversion is questionable [1, 2].

The ideal omega-3/omega-6 ratio in the body is 1:1 – 1:3, which is associated with a lower lipid count, healthier blood vessels, and reduced risk of chronic conditions [3].

DHA is highly concentrated in the brain, retina, testicles, and semen.


Essential for brain and heart health

Reduces blood triglycerides

Potent anti-inflammatory effects

Supports mental health

Improves skin health and appearance

Protects the bones and joints

Supports pregnancy and fetal development

Quickly goes rancid

Doesn’t lower blood sugar

May not help with eczema

Might interact with blood thinners

May cause fishy burps and nausea

Anti-Inflammatory Effects

Dietary omega-3 fatty acids have potent anti-inflammatory effects, and they may be beneficial for a range of inflammatory conditions [4].

In one study, men who took DHA supplements for 6-12 weeks decreased the concentrations of several inflammatory markers in their blood by approximately 20% [5].

In a study of 174 Alzheimer’s disease patients, fish oil higher in EPA than DHA lowered inflammatory cytokines, such as IL-6 and IL-1β, associated with neurodegenerative and autoimmune diseases [6].

EPA and DHA produce molecules known as “resolvins”, which are named for their ability to “resolve” inflammation. DHA also produces NPD1 molecules, which have anti-inflammatory properties in the brain [7, 8].

Studies show that dietary supplementation with fish oil lowers the activity of chronic inflammatory and autoimmune diseases including rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis, and more [9, 10].

Health Benefits

1) High Triglycerides

Both EPA and DHA have the ability to reduce triglyceride levels, most effectively after several weeks of supplementation.Reduction levels range from 15% up to 50%, and their effect is backed up by plenty of well- designed clinical trials [11, 12, 13, 14].

Many of these studies also showed their ability to increase HDL cholesterol, but the results were less consistent.

Based on these results, the FDA has approved omega-3-based prescription drugs for high triglycerides (hypertrigliceridemia): Lovaza (formerly Omacor), Omtryg, Vascepa, and Epanova [15].

It is important to note that the above formulations have a much higher EPA/DHA content than fish oil supplements, and they contain specific forms (esters) of these fatty acids. Unlike nutritional supplements, they go through rigorous quality controls by the FDA [15, 16].

The American Heart Association recommends taking 4g/daily of prescription omega-3s for optimal effects on blood triglycerides. These amounts are hard to obtain from most commercially available supplements [17].

What’s more, DHA-containing products might increase LDL cholesterol, which is not an issue with some pure-EPA prescription omega-3s [18, 16].

Possibly Effective:

2) High Blood Pressure

According to a comprehensive meta-analysis of 70 clinical trials, supplementation with omega-3s from fish oil (EPA + DHA) significantly reduces both systolic (by 2.5-5.5 mmHg) and diastolic (by 1.5-3.5 mmHg) blood pressure. The effects are more pronounced in people with moderate, untreated hypertension [19].

3) Depression

Both 1 g and 2 g of ethyl-EPA helped alleviate the symptoms of depression in 75 patients with bipolar disorder [20].

In a study of 60 depressed patients, EPA was equally effective in reducing the symptoms as an antidepressant drug fluoxetine [21].

Multiple clinical reviews and meta-analyses have found beneficial effects of fish oil/omega-3 supplementation on depression symptoms. Truth be told, the observed benefits were mild, and the researchers emphasized the low quality of the available evidence [22, 23, 24].

4) Aggression

DHA significantly reduced aggression due to mental stress in a study of 41 students. The same group of authors failed to confirm this benefit in non-stressful situations [25, 26].

In a 6-month study on 200 schoolchildren aged 8-16 years old, omega-3 supplementation caused a significant reduction in several measures of aggression [27].

5) Rheumatoid Arthritis

Resolvins found in EPA and DHA appear to prevent certain inflammatory cytokines such as TNF-α from inducing pain [28].

A meta-analysis of 17 trials found that supplemental fish oil reduces inflammatory joint pain from rheumatoid arthritis and other inflammatory conditions [29].

Omega-3’s were as effective as ibuprofen in reducing pain caused by arthritis, according to a study of 250 patients [30].

One clinical review underlined the promising benefits of fish oil for rheumatoid arthritis patients and suggested further, well-designed trials to unlock its full potential [31].

6) Skin Protection

According to preliminary research, high intake of omega-3 fats is associated with lower rates of skin cancer. Omega-3s may protect the skin by preventing the temporary suppression of the immune system caused by sunlight [32, 33].

In 42 volunteers, EPA supplementation prevented UV skin damage as seen in skin cancer [34].

Fish oil decreases skin inflammation caused by UV light in another small trial [35].

By supplying anti-inflammatory omega-3s, fish oil may prevent UV-induced skin damage. More research is needed to confirm this.

7) Painful Periods

In three studies of 380 participants, fish oil, alone or in combination with vitamin B1 or vitamin E, reduced pain, NSAID use, and quality of life in adolescent girls and women with painful periods (dysmenorrhea) [36, 37, 38].

8) Psychosis

In a study of 81 young patients with mild psychosis, low-dose omega-3 supplementation (1.2 g/day) significantly reduced the incidence of psychotic disorders [39].

Further trials should investigate this potential benefit of omega-3/fish oil.

9) Osteoporosis

Observational studies suggest that higher intake of omega-3 and lower intake of omega-6 fatty acids correlate with improved bone mineral density (BMD) in older adults [40, 41].

In a small trial of 65 older women, a combination of EPA, GLA, and calcium significantly increased BMD [42].

However, a review of 10 studies concluded that the effects of omega-3s on bone health are mild and probably stem from concurrent use of calcium and other supplements [43].

Higher intake of omega-3 fats and lower omega-6/omega-3 ratio are beneficial for bone health, but the therapeutic effects of fish oil on bone mineral density are less convincing.

10) Cachexia

Taking mega-doses (7.5-8.1 grams daily) of fish oil slightly slowed down weight loss in 67 patients with cancer-related cachexia (severe weakness and wasting) [44, 45].

Lower doses (3 grams daily) do not seem to have beneficial effects [46].

11) ADHD

According to a meta-analysis of 10 trials involving 699 children, omega-3 supplementation showed a “small but significant effect in improving ADHD symptoms.” Supplements with a higher EPA content appear to be more effective [47].

That said, a review published in 2019 regarded the benefits of fish oil for ADHD as insignificant [48].

Further research is needed to evaluate the efficacy of omega-3 fatty acids for ADHD symptoms and determine the optimal dosage and formulation.

Insufficient Evidence:

No valid clinical evidence supports the use of fish oil for any of the conditions in this section. Below is a summary of up-to-date animal studies, cell-based research, or low-quality clinical trials which should spark further investigation. However, you shouldn’t interpret them as supportive of any health benefit.

12) Stroke

Fish oil improved blood flow to the brain in 22 healthy individuals [49].

According to observational trials, increased dietary intake of fish and fish oil is associated with lower stroke rates. Data from clinical trials are less convincing; they point to mild beneficial effects on thrombotic (blood-clotting) but not hemorrhagic (bleeding) stroke [50, 51].

The brain protection likely stems from omega-3 fats, especially DHA, which combat inflammation and shield the blood vessels from clotting [52].

In 66 patients with rheumatoid arthritis, high doses of fish oil decrease disease activity and a number of tender joints, even after they discontinued NSAID treatment (diclofenac) [53].

13) Heart Health

High triglyceride levels, a risk factor for various cardiovascular diseases, are effectively reduced by EPA and DHA from fish oil [11, 12, 13].

Normalizing the is linked to cardiovascular protection [54].

Studies show that higher intakes of DHA+EPA improves omega-6/omega-3 ratio, which is associated with improved heart health. A ratio of 4:1 and lower is associated with a significant reduction of heart disease rates and different inflammatory conditions [54, 55].

Scientists are warning that we evolved with a nearly 1:1 ratio, and this ratio in a modern western diet can reach up to 16:1 [54].

According to an older review of clinical evidence, fish oil supplementation is associated with a significant reduction in mortality from heart disease [56].

However, a recent comprehensive review from the Cochrane database—79 trials of over 112,000 total participants—found no significant benefits of omega-3/fish oil supplementation on heart disease and related mortality [57].

A study published this year included 25,871 participants and came to the same conclusion [58].

Moderate fish consumption is likely to provide healthy fats and lower the risk of heart disease, but the same may not go for fish oil supplements.

14) Weight Loss

Fish oil’s anti-inflammatory effects have the ability to indirectly aid in fat metabolism in people with high inflammation or metabolic syndrome [59].

It can increase the secretion of adiponectin, which is responsible for breaking down fats [60].

In a large meta-analysis of 21 clinical trials, fish oil in combination with lifestyle changes significantly reduced waste-to-hip ratio (WHR) but failed to improve weight loss [61].

Current evidence can’t recommend fish oil as a complementary approach to weight loss. Still, obese people may benefit from its ability to reduce abdominal fat, which is a strong risk factor for heart disease [62].

15) Fertility and Fetal Development

Data suggests that fish oil may contribute to reduced reproductive aging and extended reproductive lifespan. High doses of fish oil supplementation improved markers of female reproductive lifespan 12 in women of normal weight, but had no benefits for obese women [63, 64].

The fetus of a pregnant woman requires EPA and DHA for proper development. DHA plays a significant role in the neural development of a fetus. The fetus is dependent on the mother to provide DHA, either through supplementation or diet [65, 66].

Breast milk is a significant source of DHA. A higher concentration of DHA in breast milk is connected to a mother’s diet and supplementation [67].

There is limited evidence that fish oil may reduce the risk of premature birth [68].

However, clinical trials that examined the effects of fish oil supplementation on infant development and cognition were less convincing. In two trials of 250 pregnant women, fish oil caused only minor improvements in infants’ cognition and coordination [69, 70].

The second trials followed up the infants for 12 years and found no long-term cognitive benefits of maternal fish oil supplementation [71].

16) Kidney Disease

Omega-3 supplementation improved kidney function in 97 diabetes [72].

However, it had no beneficial effects in another trial of 36 patients with diabetic nephropathy (kidney disease). More research is needed to draw a conclusion [73].

17) Inflammatory Bowel Disease

The anti-inflammatory effects of omega-3 fats may assist in managing inflammatory bowel disease (IBD) and other gastrointestinal diseases causing inflammation, but the available evidence is weak [74].

In one study, 4.2 grams of fish oil daily for 8 months reduced the symptoms of active mild-to-moderate ulcerative colitis [75].

However, a review of three clinical trials and 138 ulcerative colitis patients found no significant benefits of fish oil supplementation. The authors suggested further trials with improved fish oil formulation (enteric-coated capsules) [76].

18) Athletic Performance

Fish oil lowered heart rate and oxygen demand during exercise without interfering with performance in a study of 16 well-trained cyclists [77].

In 40 young wrestlers, fish oil (1 gram daily for 12 weeks) improved lung function compared to placebo [78].

In a study on rats, fish oil reduced the oxygen consumption of muscles, which promoted resistance to muscle fatigue [79].

On the other hand, fish oil supplements improved heart function but did not improve performance or recovery in 25 football players [80].

19) Cancer Prevention

The evidence about the role of fish oil in cancer prevention is conflicting.

According to different observational studies, increased intake of supplemental or dietary fish oil, as well as higher omega-3 blood levels, are associated with a lower risk of several cancers including skin, oral, prostate, colorectal, ovarian, and breast cancers [33, 81, 82, 83, 84].

On the other hand, some observational research and one large clinical trial (25,871 participants) failed to confirm this connection [85, 86, 87].

Well-designed should investigate this further and identify the factors contributing to mixed results. At this point, there’s insufficient evidence to suggest fish oil for cancer prevention.

20) Migraine

A recent meta-analysis of 10 clinical trials summarized the available research on fish oil/omega-3 and migraine headaches. According to the results, supplementation may not reduce frequency and severity of the attacks but may significantly reduce their duration (3.4 hours) [88].

21) Alzheimer’s Disease

Preliminary studies showed that a high intake of DHA was associated with a reduced risk of developing Alzheimer’s disease [89].

In two studies of 1,600 older participants, increased consumption of fish oil and dietary fish was associated with lower rates of Alzheimer’s [90].

Preclinical studies indicate that DHA improves memory and can slow the progression of Alzheimer’s disease in mice [91].

However, in a meta-analysis of three clinical trials and 630 Alzheimer’s patients, omega-3 supplementation didn’t improve cognitive function [92].

Fish oil may help prevent Alzheimer’s disease but may not be effective in reducing the symptoms once the disease has occurred.

22) Epilepsy (Seizures)

In 57 patients with chronic epilepsy, omega-3 supplementation (1 g EPA + 0.7 g DHA) significantly reduced seizure frequency over the first 6 weeks, but the effect was not sustained [93].

In a more recent trial of 24 patients with drug-resistant epilepsy, low-dose fish oil (3 caps/day, 1080 mg EPA+DHA) reduced seizure frequency by 33.6%. Further research is warranted [94].

23) Psoriasis

Supplementary omega-3 fatty acids improved topical treatment in 30 patients with psoriasis by improving skin rash, scaling, redness, and other symptoms [95].

In two studies of 103 patients, omega-3 injections rapidly and significantly improved skin health and psoriasis symptoms [96, 97].

However, oral fish oil was no better than corn oil or olive oil in reducing the symptoms of psoriasis in two clinical trials of over 150 patients [98, 99].

Dietary intake of fish oil is essential for skin health, but its therapeutic effects on psoriasis require further investigation.

24) Irregular Heartbeat

In a large meta-analysis of 51 trials (3,000 participants), omega-3 supplementation “mildly but significantly reduced heart rate.” DHA appears to be more effective than EPA [100].

On the other hand, two large studies failed to show the benefits of fish oil on different types of irregular heartbeat in patients with inserted devices (implantable defibrillators) [101, 102].

More studies are needed to shed light on the conflicting effects of fish oil on irregular heartbeats.

Possibly Ineffective:

Cognitive Function

Omega-3 fats are essential for brain functions and development. Higher levels of DHA are correlated with improved verbal fluency in older people and better performance in middle-aged adults [103, 104].

Fish oil and DHA supplements improved cognitive function it two smaller clinical trials with young adults [105, 106].

However, a Cochrane database review analyzed three large well-designed clinical trials of more than 3,500 older participants. The authors found no significant effects on cognitive decline in healthy elderly [107].

Two recent studies of over 700 older people came to the same conclusion [108, 109].


According to preliminary clinical evidence, fish oil supplementation may not help with:

Atherosclerosis [110, 111]

Atopic dermatitis (eczema) [112]

Atrial fibrillation (irregular heartbeat) [113]

Helicobacter pylori infection [114]

Menopausal symptoms [115]

Preeclampsia (high blood pressure during pregnancy) [116]

Likely Ineffective:


Fish oil supplementation can reduce triglycerides in diabetes patients, but multiple clinical trials found it ineffective for improving the markers of blood sugar control [117, 118, 119, 120].

Fish Oil Side Effects and Precautions

When taken in moderate amounts (up to 3 g daily), fish oil supplements are safe for a general population. They are likely safe for pregnant women and children, too, when used in doses suggested by a healthcare professional [121].

The FDA labeled dietary fish oil as GRAS (generally recognized as safe) [122].

Possible side effects are mild and include [121]:

“Fishy burps”

Bad breath




Large amounts of fish oil from dietary sources are possibly unsafe, due to the risk of contamination with environmental toxins and heavy metals. Pregnant women may be particularly sensitive to this [123].

When choosing a fish oil product, make sure to go with a trusted brand that purifies the oil and tests for contaminants. Unlike dietary supplements, prescription fish oil/omega-3 go through rigorous quality and safety controls.

High DHA doses may increase LDL cholesterol. People with high cholesterol may want to choose EPA-only formulations [18, 16].

Drug Interactions

Supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before supplementing and let them know about all drugs and supplements you are using or considering.

Drugs for weight loss (Orlistat) and oral contraceptives may hinder the absorption and reduce the effectiveness of fish oil [124, 121].

On the other hand, fish oil may enhance the effects of blood-thinners and high blood pressure drugs [125, 19].

Caution and strict medical supervision are warranted before combining fish oil with the above groups of drugs.

Fish Oil Supplementation


The below doses may not apply to you personally. If your doctor suggests using fish oil, work with them to find the optimal dosage according to your health condition and other factors.

The recommended daily dosage of fish oil supplements is 1,000-3,000 mg, depending on the condition. Adults should get at least two servings of oily fish per week, which is equivalent to about 500mg of omega-3 fats. Maximal results occur after approximately three weeks of taking supplements [126].

Some people respond better to high doses of fish oil. Maximum effects on triglyceride levels may require 4 g of prescription omega-3s daily [17].

Fish oil supplements: do they have a role in the management of rheumatoid arthritis?

Omega-3 fatty acids found in marine fish oil may help to reduce inflammation in the joints and improve the symptoms of rheumatoid arthritis for some people. Having less severe symptoms may allow you to reduce the doses of other medicines you take for rheumatoid arthritis. Fish oil supplements may take up to 3 months for maximal effectiveness, so you may need to take other pain relief medicines in the meantime. These include non-steroidal anti-inflammatory drugs (eg, aspirin, ibuprofen, diclofenac) and steroids (eg, prednisone). However, it is important that you do not stop taking your other medicines or reduce the doses without speaking to your doctor first.

Supplements vary in the amount of omega-3 they contain. If you have rheumatoid arthritis the recommended daily intake of omega-3 in fish oil is at least 2.7 g. This is the same as taking between 6 and 9 capsules or 1–3 teaspoons of liquid per day. Serious side effects from fish oil supplements are rare at these doses but minor side effects may include nausea and a rash.

Gastrointestinal adverse effects of fish oil include heartburn, diarrhoea and a fishy aftertaste. . Taking the capsules with food or keeping them in the freezer can help reduce this aftertaste.

Extra caution should be taken with fish liver oils such as cod liver oil as they contain high levels of vitamin A. High intake of vitamin A in the diet can be toxic. For this reason, take omega-3 supplements from fish body oil rather than fish liver oil.

Eric Carter