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Humans can convert short-chain omega−3 fatty acids to long-chain forms (EPA, DHA) with an efficiency below 5%.[73][74] The omega−3 conversion efficiency is greater in women than in men, but less studied.[75] Higher ALA and DHA values found in plasma phospholipids of women may be due to the higher activity of desaturases, especially that of delta-6-desaturase.[76]

A 2008 meta-study by the Canadian Medical Association Journal found fish oil supplementation did not demonstrate any preventative benefit to cardiac patients with ventricular arrhythmias.[36] A 2012 meta-analysis published in the Journal of the American Medical Association, covering 20 studies and 68,680 patients, found that Omega-3 Fatty Acid supplementation did not reduce the chance of death, cardiac death, heart attack or stroke.[37]

Dornstauder, B., Suh, M., Kuny, S., Gaillard, F., MacDonald, I., Michael T. Clandinin, M. T., & Sauvé, Y. (2012, June). Dietary docosahexaenoic acid supplementation prevents age-related functional losses and A2E accumulation in the retina. Investigative Ophthalmology and Visual Science. Retrieved from http://iovs.arvojournals.org/article.aspx?articleid=2188773


A healthy balance of dietary omega 6 and omega 3 fatty acids is a prerequisite for normal immune function, cognitive health, and cardiovascular health. Among other factors, sufficient dietary levels of EPA, DHA or other omega 3 fatty acids are also important in the regulation of normal blood lipoprotein and healthy cholesterol metabolism. Fish oil supplements can also lower elevated triglyceride levels, improving cardiovascular health and reducing the risk of heart disease.†
So why is an excess of DHA detrimental and an excess of EPA useful? DHA has a larger structure with two extra carbons and two extra double bonds, so it literally takes up more space in cell membranes than EPA. On the one hand, this is important because DHA plays a structural role in maintaining the fluidity of cell membranes ( essential for the normal function of proteins, channels and receptors that are also embedded in the membrane), but if a cell membrane becomes too saturated with DHA it can become too fluid, which can have a negative effect on cell function. EPA, on the other hand, is constantly utilised and always in demand.
Mercury and polychlorinated biphenyls (PCBs) are common toxins in seafood. Although the U.S. banned the use of PCBs and DDT in 1976, these and other chemicals are still used in half the world's commercial chemical processes. Substances like these can hang around in the air, soil, and water for many years. They end up in the bodies of fish and animals.
Several other analyses of the evidence have been done in the last few years (2012 or later), and like the 2018 analysis and the AHRQ report, most found little or no evidence for a protective effect of omega-3 supplements against heart disease. However, some earlier analyses suggested that omega-3s could be helpful. The difference between the newer conclusions and the older ones may reflect two changes over time: 
Evidence linking fish oil and cancer has been all over the map. Some research suggests diets high in fatty fish or fish oil supplements might reduce the risk of certain cancers, including prostate cancer. Other research shows just the opposite, a  link between eating a lot of oily fish or taking potent fish oil supplements and a 43% increased risk for prostate cancer overall, and a 71% increased risk for aggressive prostate cancer.

On September 8, 2004, the U.S. Food and Drug Administration gave "qualified health claim" status to EPA and DHA omega−3 fatty acids, stating, "supportive but not conclusive research shows that consumption of EPA and DHA [omega−3] fatty acids may reduce the risk of coronary heart disease".[98] This updated and modified their health risk advice letter of 2001 (see below).
Krill oil is joining the toolkit for fighting arthritis, thanks to its exceptional anti-inflammatory properties resulting from its phospholipid form of omega-3s. A study in mice with experimental arthritis showed that krill oil supplements reduced arthritis scores and markedly diminished joint swelling. When examined under a microscope, the animals’ joints were remarkably free of inflammatory infiltrates of immune system cells.85

Consumers of oily fish should be aware of the potential presence of heavy metals and fat-soluble pollutants like PCBs and dioxins, which are known to accumulate up the food chain. After extensive review, researchers from Harvard's School of Public Health in the Journal of the American Medical Association (2006) reported that the benefits of fish intake generally far outweigh the potential risks.

This systematic review and meta-analysis of clinical trials conducted on participants with clinical anxiety symptoms provides the first meta-analytic evidence, to our knowledge, that omega-3 PUFA treatment may be associated with anxiety reduction, which might not only be due to a potential placebo effect, but also from some associations of treatment with reduced anxiety symptoms. The beneficial anxiolytic effects of omega-3 PUFAs might be stronger in participants with specific clinical diagnoses than in those without specific clinical conditions. Larger and well-designed clinical trials should be performed with high-dose omega-3 PUFAs, provided as monotherapy and as adjunctive treatment to standard therapy.
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.
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We’ve already seen that fish oil can help with depression-like symptoms in rats, but what about people? A study published in the journal Nutritional Neuroscience evaluated the effects of fish oil supplementation on prefrontal metabolite concentrations in adolescents with major depressive disorder. Researchers found that there was a 40 percent decrease in major depression disorder symptoms in addition to marked improvements in amino acid and nutrition content in the brain, specifically, the right dorsolateral prefrontal cortex. (21)


DHA is one of the most prevalent fatty acids in the brain. This could partly explain why our brains do better with a greater supply. A Rush Institute for Healthy Aging study analyzed fish-eating patterns of more than 800 men and women, ages 65 to 94. Those eating fish at least once a week were much less likely to develop Alzheimer's disease than those who turned up their nose at it.
Various scales were used in these studies to evaluate the target outcome of anxiety symptoms: the Yale-Brown Obsessive-Compulsive Scale, Profile of Mood States, State-Trait Anxiety Inventory, Hamilton Anxiety Rating Scale, Generalized Anxiety Disorder questionnaire, Depression, Anxiety, and Stress Scales, Clinician-Administered Posttraumatic Stress Disorder Scale, Beck Anxiety Inventory, visual analog scale of anxiety, Impact of Event Scale–Revised, Conners score anxiety subscale, Neuropsychiatric Inventory, test anxiety severity, Hospital Anxiety and Depression Scale anxiety subscale, and Child Behavior Checklist anxiety subscale. The psychiatric and physical health conditions of the recruited participants also varied widely: general population without specific clinical conditions,36,47,51,55,60 participants with acute myocardial infarction,35 borderline personality disorder,2 mild to severe depression,59 obsessive-compulsive disorder,33 severe accidental injury,49 participants who were traumatized by disaster,54 participants with substance abuse disorder,34 women with premenstrual syndrome,56 children with attention-deficit/hyperactivity disorder,48,53 Alzheimer disease,58 generally healthy undergraduate college students but with test anxiety,61 Parkinson disease,52 and participants with Tourette syndrome.57 Sixteen studies compared the effect of omega-3 PUFA treatment with that of the placebo33,34,36,47-49,51-53,55-61; the other 3 studies were non–placebo controlled trials.35,50,54 The mean (SD) Jadad score of the recruited studies was 3.8 (1.0) (eTable in the Supplement).
Although there was significant heterogeneity among the included studies (Cochran Q, 178.820; df, 18; I2, 89.934%; P < .001), the sensitivity test suggested that the main significant results of the meta-analysis would not change after removal of any of the included studies. However, through direct inspection of the forest plot, we detected the potential influence of some outliers, such as the studies by Sohrabi et al56 and Yehuda et al.61 These 2 studies evaluated anxiety symptoms with a visual analog scale of anxiety and test anxiety severity, which are seldom used in psychiatric research and lack a definite report to prove their equivalent sensitivity and specificity to some other frequently used anxiety rating scales, such as depression, anxiety, and stress scales or the Hamilton anxiety rating scale. Therefore, these studies might have affected the interpretation of the current meta-analysis.

Dyerberg, J., Eskesen, D. C., Andersen, P. W., Astrup, A., Buemann, B., Christensen, J. H., Clausen, P., Rasmussen, B. F., Schmidt, E. B., Tholstrup, T., Toft, E., Toubro, S., and Stender, S. Effects of trans- and n-3 unsaturated fatty acids on cardiovascular risk markers in healthy males. An 8 weeks dietary intervention study. Eur.J.Clin.Nutr. 2004;58(7):1062-1070. View abstract.

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The systematic review suggests that eating more ALA through food or supplements probably has little or no effect on cardiovascular deaths or deaths from any cause. However, eating more ALA probably reduces the risk of heart irregularities from 3.3 to 2.6%. The review team found that reductions in cardiovascular events with ALA were so small that about 1000 people would need to increase consumption of ALA for one of them to benefit. Similar results were found for cardiovascular death. They did not find enough data from the studies to be able to measure the risk of bleeding or blood clots from using ALA.
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.
Some high-quality omega-3 supplements will have lower amounts than EPA/DHA but accompany them with digestive enzymes. While it looks counterintuitive on a nutrition label, this is often done because there is debate about how much of the omega-3’s you actually absorb from supplements when taken alone. By coupling omega-3’s with a digestive enzyme blend, you are likely able to absorb more of the nutrient without having to consume as many grams.
Because patients with depression experience rapid shrinking of their hippocampus, many strategies for relieving depression focus on increasing new brain cell growth in that specific area of the brain.23 There’s now evidence that increasing omega-3 intake, especially DHA, may be an effective way of treating or preventing depression, partly by protecting the hippocampus from further shrinkage.23
People with metabolic syndrome (the combination of central obesity, high blood pressure, disturbed lipid profile, and impaired glucose tolerance) are at increased risk of death from cardiovascular disease, diabetes, cancer, and other apparently “age-related” disorders. Because metabolic syndrome is closely associated with chronic low-grade inflammation, the powerful anti-inflammatory effects of omega-3 fats are especially important as a means of slowing or stopping the progression of this deadly disorder.
Fish oil supplements in our study averaged 473.3mg EPA + 243.1mg DHA in a single serving. These average values were stretched by outliers on both extremes of the spectrum. Nature Made Cod Liver Oil (50mg EPA/serving) and Schiff MegaRed Krill Oil (29mg DHA/serving) recorded category lows for the two omega-3 fatty acids. Ocean Blue Professional Omega-3 (1260mg EPA/serving) and Dr. Tobias Optimum Omega-3 Fish Oil (600mg DHA/serving), on the other hand, recorded category highs for EPA and DHA content.
These low levels are especially bad when compared to the numbers from the Japanese population. In Japan, the average omega-3 index level is more than double that of the average American, with some surveys showing Japanese men consume over 100 g (approximately 3.5 oz) of fish every day. These radically different dietary habits help explain how even those with omega-3 indexes in the lowest 5th percentile of the Japanese population have higher omega-3 index averages than most Americans (8).

If you find yourself in a position where you are just not eating any of these foods, and you want to get enough omega-3 fatty acids, then I think fish oil is okay, but I would limit not the amount of fish oil but the amount listed on the label of EPA and DHA combined. I would limit that amount to around 250 milligrams per day because I don’t think most people need more than that. Some signs that you might not be getting enough omega-3 fatty acids include chronic low-grade inflammation, poor visual acuity, slower mental processing, trouble learning, and possibly Alzheimer’s disease and psychiatric conditions, like depression, anxiety, and attention deficit and hyperactivity disorder, ADHD.
Tanaka, K., Ishikawa, Y., Yokoyama, M., Origasa, H., Matsuzaki, M., Saito, Y., Matsuzawa, Y., Sasaki, J., Oikawa, S., Hishida, H., Itakura, H., Kita, T., Kitabatake, A., Nakaya, N., Sakata, T., Shimada, K., and Shirato, K. Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: subanalysis of the JELIS trial. Stroke 2008;39(7):2052-2058. View abstract.
Weight loss. Some research shows that eating fish improves weight loss and decreases blood sugar in people who are overweight with high blood pressure. Early research also shows that taking a specific fish oil supplement (Hi-DHA, NuMega) lowers body fat when combined with exercise. But other evidence suggests that taking another specific fish oil supplement (Lovaza) does not lower body weight in overweight people.
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