Flaxseed (or linseed) (Linum usitatissimum) and its oil are perhaps the most widely available botanical source of the omega−3 fatty acid ALA. Flaxseed oil consists of approximately 55% ALA, which makes it six times richer than most fish oils in omega−3 fatty acids.[126] A portion of this is converted by the body to EPA and DHA, though the actual converted percentage may differ between men and women.[127]
Omega-3 fatty acids have been found to play a role in atherosclerosis and peripheral arterial disease (PAD). It is thought that both EPA and DHA improve plaque stability, decrease endothelial activation, and improve vascular permeability, thereby decreasing the chance of experiencing a cardiovascular event (41). It was found that EPA supplementation is associated with significantly higher amounts of EPA in the carotid plaque than placebo (P < 0.0001), which may lead to decreased plaque inflammation and increased stability (42). PAD, a manifestation of atherosclerosis, is characterized by buildup of plaque in the arteries of the leg and can eventually lead to complete blockage of the arteries. EPA+DHA supplementation has been shown to improve endothelial function in patients with PAD by decreasing plasma levels of soluble thrombomodulin from a median value of 33.0 μg/L to 17.0 μg/L (P = 0.04) and improve brachial artery flow–mediated dilation from 6.7% to 10.0% (P = 0.02) (43). Patients who had PAD and were supplemented with EPA experienced a significantly lower major coronary event HR than those who did not take EPA (HR: 0.44; 95% CI: 0.19–0.97; P = 0.041) (44).

For patients without documented CAD, the American Heart Association 2006 Diet and Lifestyle Recommendations advise the consumption of at least 2 servings of fish per week, preferably fatty fish high in DHA and EPA.65 The guidelines also recommend a daily fish intake equivalent to 1 g/d of EPA and DHA for secondary prevention of CAD. Fish oil supplements containing EPA and DHA are suggested as an alternative to fatty fish consumption for secondary prevention.
Good for you for eating healthily! Sadly, many people do not like omega-3 containing foods such as fish, and for these people, supplementation may be a good alternative to obtain omega-3. As a clinical investigator, my research focuses on study supplements, which is what I was asked to cover in this article. I’m all for healthy eating, but not everyone can afford it or wants to eat certain foods, and this is perhaps why supplements are so popular.
There is some evidence that omega−3 fatty acids are related to mental health,[47] including that they may tentatively be useful as an add-on for the treatment of depression associated with bipolar disorder.[48] Significant benefits due to EPA supplementation were only seen, however, when treating depressive symptoms and not manic symptoms suggesting a link between omega−3 and depressive mood.[48] There is also preliminary evidence that EPA supplementation is helpful in cases of depression.[49] The link between omega−3 and depression has been attributed to the fact that many of the products of the omega−3 synthesis pathway play key roles in regulating inflammation (such as prostaglandin E3) which have been linked to depression.[50] This link to inflammation regulation has been supported in both in vitro[51] and in vivo studies as well as in meta-analysis studies.[33] The exact mechanism in which omega−3 acts upon the inflammatory system is still controversial as it was commonly believed to have anti-inflammatory effects.[52]
Causing unsafe conditions. Fish oil may increase the risk of bleeding, which can lead to an unsafe condition. Excessive bleeding inside the body may also lead to conditions such as ulcers or liver disease which could be quite dangerous. Be aware of the signs and symptoms of this condition such as bruising easily or nosebleeds which could be a sign that you are developing this condition. If you begin to bleed more easily than usual then you should reduce the amount of fish oil you take regularly to reduce this condition.
The DART study, published in 1989, was the first randomized trial to show the efficacy of fish oil on CAD.37 In the trial, 2033 post-MI patients were randomized to receive 3 types of diets: a diet that was either high in cereal fiber, polyunsaturated fat, or fish oil. The fish oil group consumed 200 to 400 g/wk of fatty fish (2 portions of fish per week) or 0.5 g/d of Maxepa fish oil supplement. At 2 years, the primary end point of all-cause mortality was reduced by 29% in the fish oil group, whereas no improvement was seen in the other dietary advice groups.
Australian researchers published results of a study examining the effects of fish oil on weight loss in combination with diet and exercise in the May 2007 issue of American Journal of Clinical Nutrition. The results show that a combination of fish oil supplements and regular exercise can reduce body fat while also improving heart and metabolic health. The fish supplementation group had lowered triglycerides, increased HDL cholesterol and improved blood flow. Overall, adding fish oil to a current exercise program (and a overall healthy lifestyle) looks like it can decrease body fat as well as cardiovascular disease risk. (32)
A scientific review published in 2013 looked at omega-3 polyunsaturated fatty acids and prostate cancer prevention. Researchers concluded that there’s a great deal of evidence suggesting that omega-3s have antiproliferative effects – which means they inhibit cancer cell growth – in cancer cell lines, animal models and humans. In addition, the “direct effects on cancer cells” and indirect anti-inflammatory effects on the immune system fighting the cancer likely contribute to the ability of omega-3 fatty acids to inhibit tumor growth. (14)
The GISSI-Heart Failure trial was the first blinded, randomized trial to assess the efficacy of fish oil supplements in patients with heart failure.51 The trial enrolled 7046 subjects with heart failure; 60% with New York Heart Association class II symptoms and 40% with a history of MI. The majority of patients were on a standard heart failure regimen, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, and spironolactone, but only 22% were on a statin. At an average of 3.9 years, the coprimary end points of death and death or hospital admission for cardiovascular reasons were reduced by approximately 9% with fish oil supplementation. Sudden cardiac death, a secondary end-point, showed a statistically nonsignificant relative risk reduction of 7% with fish oil. There was also a reduction in 2 other arrhythmia-related secondary end-points: first hospitalization for ventricular arrhythmia and presumed arrhythmic death.
The human body can make most of the types of fats it needs from other fats or raw materials. That isn’t the case for omega-3 fatty acids (also called omega-3 fats and n-3 fats). These are essential fats—the body can’t make them from scratch but must get them from food. Foods high in Omega-3 include fish, vegetable oils, nuts (especially walnuts), flax seeds, flaxseed oil, and leafy vegetables.
Badia-Tahull, M. B., Llop-Talaveron, J. M., Leiva-Badosa, E., Biondo, S., Farran-Teixido, L., Ramon-Torrell, J. M., and Jodar-Masanes, R. A randomised study on the clinical progress of high-risk elective major gastrointestinal surgery patients treated with olive oil-based parenteral nutrition with or without a fish oil supplement. Br.J.Nutr. 2010;104(5):737-741. View abstract.
Most Americans take in far more of another essential fat—omega-6 fats—than they do omega-3 fats. Some experts have raised the hypothesis that this higher intake of omega-6 fats could pose problems, cardiovascular and otherwise, but this has not been supported by evidence in humans. (4) In the Health Professionals Follow-up Study, for example, the ratio of omega-6 to omega-3 fats wasn’t linked with risk of heart disease because both of these were beneficial. (5) Many other studies and trials in humans also support cardiovascular benefits of omega-6 fats. Although there is no question that many Americans could benefit from increasing their intake of omega-3 fats, there is evidence that omega-6 fats also positively influence cardiovascular risk factors and reduce heart disease.
The differing actions of EPA and DHA, together with their competitive uptake, help to explain why studies that attempt to use standard fish oil therapeutically (where DHA and EPA are combined, in a natural ratio of approximately 1.5:1) are either less beneficial than expected, or even completely ineffective. Standard EPA/DHA fish oils are more suitable for everyday wellbeing, to compensate for a lack of fish in the diet and to meet a suggested intake.
Badia-Tahull, M. B., Llop-Talaveron, J. M., Leiva-Badosa, E., Biondo, S., Farran-Teixido, L., Ramon-Torrell, J. M., and Jodar-Masanes, R. A randomised study on the clinical progress of high-risk elective major gastrointestinal surgery patients treated with olive oil-based parenteral nutrition with or without a fish oil supplement. Br.J.Nutr. 2010;104(5):737-741. View abstract.
Jump up ^ Kwak SM, Myung SK, Lee YJ, Seo HG (May 2012). "Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials". Archives of Internal Medicine. 172 (9): 686–94. doi:10.1001/archinternmed.2012.262. PMID 22493407.

Whilst EPA and DHA are both considered to be important regulators of immunity, platelet aggregation and inflammation, their health-influencing by-products arise from very different pathways and their effects in the body differ. DHA is the most abundant omega-3 fatty acid in cell membranes, present in all organs and most abundant in the brain and retina, playing an important structural role. EPA is present structurally only in minute quantities, always being utilised and under constant demand to be replaced. Whilst DHA provides mainly a structural role, it is becoming evident that EPA may be the dominant functional fatty acid out of the two in many areas of health and especially in inflammatory conditions.
A, Subgroup meta-analysis of the anxiolytic effect of omega-3 polyunsaturated fatty acids (PUFAs) based on an underlying specific clinical diagnosis or not. The anxiolytic effect of omega-3 PUFAs was not significant in the subgroup of participants without specific clinical conditions (k, 5; Hedges g, –0.008; 95% CI, –0.266 to 0.250; P = .95) but was significant in the subgroup of participants with specific clinical diagnoses (k, 14; Hedges g, 0.512; 95% CI, 0.119-0.906; P = .01). Furthermore, the association of treatment with reduced anxiety symptoms of omega-3 PUFAs were significantly stronger in subgroups with specific clinical diagnoses than in subgroups without specific clinical conditions (P = .03). B, Subgroup meta-analysis of the anxiolytic effect of omega-3 PUFAs based on different mean omega-3 PUFA dosages. The anxiolytic effect of omega-3 PUFAs was not significant in subgroups of mean omega-3 PUFA dosages less than 2000 mg/d (k, 9; Hedges g, 0.457; 95% CI, –0.077 to 0.991; P = .09) but was significant in the subgroup of mean omega-3 PUFA dosage of at least 2000 mg/d (k, 11; Hedges g, 0.213; 95% CI, 0.031-0.395; P = .02).
Fish oil is also commonly used to treat conditions such as Rheumatoid arthritis, high blood pressure, ADHD, menstrual pain, hardening of the arteries or kidney problems. These conditions can be improved by improving blood flow, which omega-3 fatty acids in the blood stream. There is also some evidence that fish oil may help with conditions such as chest pain, liver disease, migraine prevention, gum infections, breast pain, and muscle soreness due to exercise, skin rashes and stomach ulcers.
Mozaffarian D, Marchioli R, Macchia A, Silletta MG, Ferrazzi P, Gardner TJ, Latini R, Libby P, Lombardi F, O'Gara PT, Page RL, Tavazzi L, Tognoni G; OPERA Investigators. Fish oil and postoperative atrial fibrillation: the Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial. JAMA 2012;308(19):2001-11. View abstract.
Maclean, C. H., Mojica, W. A., Morton, S. C., Pencharz, J., Hasenfeld, Garland R., Tu, W., Newberry, S. J., Jungvig, L. K., Grossman, J., Khanna, P., Rhodes, S., and Shekelle, P. Effects of omega-3 fatty acids on lipids and glycemic control in type II diabetes and the metabolic syndrome and on inflammatory bowel disease, rheumatoid arthritis, renal disease, systemic lupus erythematosus, and osteoporosis. Evid.Rep.Technol.Assess.(Summ.) 2004;(89):1-4. View abstract.
Three randomized trials assessing more than 600 patients with known malignant ventricular arrhythmia were carried out under the protection of implanted cardioverter defibrillator (ICD) therapy.41–43 In all 3 of the trials, 75% of the patients had ischemic heart disease, survived ventricular tachycardia or ventricular fibrillation and were randomized to 1 to 3 g/d of fish oil. In the first trial of its kind, 402 patients with ICDs were randomized to either a fish oil or an olive oil supplement.41 Although statistical significance was not reached, after approximately 1 year the primary end-point of time to first ICD cardioversion for ventricular tachycardia or fibrillation or death from any cause was longer in the fish oil group. This finding was not replicated in a trial of 200 patients who were randomized to either fish oil or a placebo and followed for a median of approximately 2 years.42 In fact, time to first ICD cardioversion was not changed and the incidence of recurrent ventricular tachycardia and fibrillation was more common in the group assigned to fish oil. In the largest trial, 546 patients were randomized to supplemental fish oil or a placebo and were followed for a mean period of 1 year.43 The primary outcome of the rate of ICD cardioversion or all-cause mortality was not reduced. It was concluded in a recent meta-analysis of these trials that fish oil did not have a protective effect.44
A Pregnancy Prerequisite: Omega-3 fatty acids directly affect brain development, making it crucial for expectant mothers. Additionally, research indicates they decrease a mother's risk of depression. When the mother doesn't have enough of these essential fatty acids, the baby borrows from her. Some prenatal vitamins now include omega-3s, so be sure to check the label or grab a handful of walnuts each day.
Healthy cells require a delicate balance of EPA and DHA and the body employs clever mechanisms to support this natural equilibrium. DHA levels are self-regulated through inhibiting the activity of the enzyme delta-6 desaturase – the very enzyme that supports the conversion of EPA into DHA – to ensure levels of DHA do not become too high. It is therefore possible to have too much preformed DHA, if our supplement intake exceeds the body’s needs.
^ Jump up to: a b Casula M, Soranna D, Catapano AL, Corrao G (August 2013). "Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: A meta-analysis of randomized, placebo controlled trials [corrected]". Atherosclerosis. Supplements. 14 (2): 243–51. doi:10.1016/S1567-5688(13)70005-9. PMID 23958480.
Other suspected health benefits of omega-3s and fish are less well established and need further study. They include suggestions of a reduced risk of breast cancer, colorectal cancer and possibly advanced prostate cancer, all related to eating fish rather than taking supplements. Some observational studies have associated omega-3s to a lower risk of cognitive decline, Alzheimer’s disease and dementia, as well as age-related macular degeneration.
Scaly, itchy skin (eczema). Fish oil might help PREVENT eczema, but research is not consistent. Some early research suggests that mothers who take fish oil supplements during pregnancy reduce the risk of severe eczema in their infants. Also, population research suggests that children who eat fish at least once weekly from 1 to 2 years of age have a lower risk of developing eczema. But other research, including recent studies, suggests that neither supplementation during pregnancy nor supplementation during infancy reduces the risk of eczema. Overall, research suggests that fish oil does not help TREAT eczema once it has developed.
Fish and omega-3 fatty acids. If you keep up with the latest nutrition news, you may have a pretty good sense of what they offer. But, if you're like many people, you still can't tell your omega-3s from your omega-6s -- and you sure as heck can't pronounce eicosapentaenoic acid. That's OK. Our fishing expedition turned up some interesting facts to share about omega-3 fatty acids and fish.
Rondanelli, M., Giacosa, A., Opizzi, A., Pelucchi, C., La, Vecchia C., Montorfano, G., Negroni, M., Berra, B., Politi, P., and Rizzo, A. M. Effect of omega-3 fatty acids supplementation on depressive symptoms and on health-related quality of life in the treatment of elderly women with depression: a double-blind, placebo-controlled, randomized clinical trial. J.Am.Coll.Nutr. 2010;29(1):55-64. View abstract.
Full citation: Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KHO, AlAbdulghafoor FK, Summerbell CD, Worthington HV, Song F, Hooper L. Omega 3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2018, Issue 7. Art. No.: CD003177. DOI: 10.1002/14651858.CD003177.pub3.
The effect of fish oil consumption on prostate cancer is controversial,[28][29] as one study showed decreased risk with higher blood levels of DPA, whereas another reported increased risk of more aggressive prostate cancer with higher blood levels of combined EPA and DHA.[30] Some evidence indicated an association between high blood levels of omega-3 fatty acids and an increased prostate cancer risk.[31]
In some cases, fish oil pills may cause loose stools, nausea, diarrhea, and decreased appetite, fat in the stools, vomiting or constipation. These side effects can be minimized by taking a fish oil capsule that is coated, which is designed to help eliminate the "fish burps" many users complain about. Starting with low doses of the supplement and working up to a full dose can also help minimize side effects. You can also pair fish oil supplements with meals so that they enter your body more slowly, minimizing the risk of side effects occurring.

The omega-3 index may also be helpful for assessing health risks beyond cardiovascular disease. Studies are currently investigating the relationship between omega-3 index levels and mental health issues, like depression (15, 16, 17), cognitive functioning (18, 19), body weight (20), as well as eye health issues, like macular degeneration (21), to name just a few.


Most U.S. adults fail to consume adequate amounts of foods rich in EPA and DHA on a regular basis (at least 8 ounces of fatty fish per week is recommended), and probably consume too many omega-6 fats in comparison (soybean oil, canola oil, cottonseed oil, etc.). This omega-3:omega-6 imbalance can have a negative effect on inflammation patterns and may also be implicated as a contributing factor to other processes related to cellular metabolism, hormone signaling, and even weight regulation.
To date, no studies have assessed mortality or nonfatal MI in diabetic patients treated with fish oil.52–54 A recent comprehensive meta-analysis analyzed the effect of fish oil supplements on metabolic parameters when added to usual care in patients with type 2 diabetes mellitus or impaired glucose tolerance.54 The meta-analysis included a total of 23 small, randomized trials with over 1000 patients that were assessed for lipid and insulin resistance parameters. At a mean follow-up of approximately 9 weeks, triglyceride reduction was accomplished but no significant changes were seen in total cholesterol, high-density lipoprotein-cholesterol, HgA1c levels, fasting glucose levels, fasting insulin, or in body weight. The largest randomized trial to date assessed approximately 400 patients with impaired glucose tolerance or insulin-dependent diabetes mel-litus, and as reflected in the larger meta-analysis, found no effect of moderate to high doses of fish oil on diabetic parameters.55 There are insufficient randomized data to comment on the combination of fish oil and specific diabetes medications and related mortality and/or morbidity.
Ozaydin, M., Erdogan, D., Tayyar, S., Uysal, B. A., Dogan, A., Icli, A., Ozkan, E., Varol, E., Turker, Y., and Arslan, A. N-3 polyunsaturated fatty acids administration does not reduce the recurrence rates of atrial fibrillation and inflammation after electrical cardioversion: a prospective randomized study. Anadolu.Kardiyol.Derg. 2011;11(4):305-309. View abstract.
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