McNamara, R. K., Able, J., Jandacek, R., Rider, T., Tso, P., Eliassen, J. C., Alfieri, D., Weber, W., Jarvis, K., DelBello, M. P., Strakowski, S. M., and Adler, C. M. Docosahexaenoic acid supplementation increases prefrontal cortex activation during sustained attention in healthy boys: a placebo-controlled, dose-ranging, functional magnetic resonance imaging study. Am J Clin Nutr 2010;91(4):1060-1067. View abstract.
Soy can get a bad rap — and may indeed cause problems for people with certain food sensitivities — but this delicious bean is one of the most powerful (and versatile) ways to add omega-3 to your diet. Whole soybeans (known as edamame) are a favorite protein-packed snack for vegetarians; more processed forms (including tofu, soy milk, and soybean-based cooking oil) make soy infinitely more accessible. For some ideas, check out the 1998 classic, The Whole Soy Cookbook, which outlines how to cook with soy-based products ranging from miso to tempeh and beyond.
Fish oil combined with fenofibrate has not been studied extensively in randomized controlled trials. Data to date, however, suggest that the combination is safe and effective.63,64 A recent randomized controlled trial of 100 patients with severe hypertriglyceridemia and HIV on highly active antiretroviral therapy showed that a regimen of fenofibrate and 3 g/d of fish oil for 8 weeks was well tolerated. The median baseline triglyceride level of 650 mg/dL was reduced by 65%.63 Another recent randomized, 2 month, double-blind, placebo-controlled trial, which was set up to assess the safety and efficacy of fenofibrate with 4 g of fish oil, showed that in the 81 patients assigned to combination therapy, triglyceride levels were reduced by 61%. Therapy was well-tolerated without significant adverse reactions at 8 weeks or at the end of a 2-year open label extension.64 The combination of fish oil and niacin requires further study.
Omega-3 [(n-3)] long-chain PUFA, including EPA and DHA, are dietary fats with an array of health benefits (1). They are incorporated in many parts of the body including cell membranes (2) and play a role in antiinflammatory processes and in the viscosity of cell membranes (3, 4). EPA and DHA are essential for proper fetal development and healthy aging (5). DHA is a key component of all cell membranes and is found in abundance in the brain and retina (6). EPA and DHA are also the precursors of several metabolites that are potent lipid mediators, considered by many investigators to be beneficial in the prevention or treatment of several diseases (7).
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.
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.
There’s more good news when it comes to fish oil and eye health, and it’s just not just for diabetic this time. Fish oil has been shown to reverse age-related eye disorders. In March 2014, French researchers evaluated 290 patients with age-related macular degeneration (AMD), and they discovered that dietary oil fish and seafood intake were significantly lower in AMD patients. Due to the high EPA and DHA levels in fish oil, it was concluded that this kind of nutritional intervention could especially benefit those at high risk for neovascular age-related macular degeneration. (24)

Fish oil can be consumed in various ways such as capsules or can be included in daily meals. The dosage should not exceed 3 fish oil capsules per day. 1000mg of fish oil contains approximately 300mg omega-3 fatty acids so you can accordingly use the amount of fish oil in your meals. A daily intake of 3000mg or less is safe for all. Pregnant and lactating women can consume approximately 3200 mg per day.


Doses for depression range from less than 1 g/day to 10 g/day, but most studies use doses between 1 and 2 g/day. In my practice, I recommend 1 to 2 g/day of an EPA+DHA combination, with at least 60% EPA, for major depression. I am more cautious in patients with bipolar depression, because the omega-3s may bring on mania, as can most antidepressants. In these individuals, I recommend using omega-3 cautiously, and preferably in combination with a prescription mood stabilizer.
The various enzymes (COX and LOX) that make inflammatory eicosanoids can accommodate both AA and EPA, but again due to the greater spatial size of DHA, these enzymes will have difficulty in converting DHA into eicosanoids. This makes DHA a poor substrate for these key inflammatory enzymes. Thus DHA again has little effect on cellular inflammation whereas EPA can have a powerful impact.
Peroxides can be produced when fish oil spoils. A study commissioned by the government of Norway concluded there would be some health concern related to the regular consumption of oxidized (rancid) fish/marine oils, particularly in regards to the gastrointestinal tract, but there is not enough data to determine the risk. The amount of spoilage and contamination in a supplement depends on the raw materials and processes of extraction, refining, concentration, encapsulation, storage and transportation.[51] ConsumerLab.com reports in its review that it found spoilage in test reports it ordered on some fish oil supplement products.[52]
The chemical structure of eicosapentaenoic acid and docosahexaenoic acid. Eicosapentaenoic acid consists of 20 carbons (C20) with 5 double bonds, and the last unsaturated carbon is located third from the methyl end (n-3). Do-cosahexaenoic acid consists of 22 carbons (C22) with 6 double bonds, and also with the3 last unsaturated carbon located third from the methyl end (n-3). Adapted with permission from Frishman et al, eds. Cardiovascular Pharmacotherapeutics. New York, NY: McGraw Hill; 2003.3
Most leafy green vegetables have significant amounts of omega-3, and spinach is no exception. Despite its villainous reputation, raw spinach actually has a mild flavor, making it an ideal base for salads or a crunchy addition to sandwiches. Many people add spinach to eggs, soups, or pasta dishes without impacting flavor. If you’re dealing with a particularly picky eater, though, try some of the recipes in Jessica Seinfeld’s Deceptively Delicious — her spinach and carrot brownies are tasty, healthy, and chocolaty to boot!
If you’re not able to get enough fish oil benefits through your diet, fish oil supplements can be a good option. Fish oil side effects can include belching, bad breath, heartburn, nausea, loose stools, rash and nosebleeds, but in my experience, taking a high-quality fish oil supplement can reduce the likelihood of any unwanted side effects. It’s also a good idea to take fish oil with meals to reduce side effects.
Due to the presence of Omega-3 fatty acids, fish oil has been promoted for relieving depression, sadness, anxiety, restlessness, mental fatigue, stress, decreased sexual desire, suicidal tendencies, and other nervous disorders. Researchers at the Case Western Reserve University School of Medicine in Cleveland, Ohio, in their research publication titled “Fish Oils and Bipolar Disorder: A Promising but Untested Treatment”, state that fish oil can be useful in mood stabilization and the treatment of bipolar disorders. It is unsurprising, therefore, that countries where fish is frequently eaten, have a low incidence of depression. Similarly, research conducted on prisoners has shown that when prisoners were given seafood containing a higher amount of omega-3 fatty acids, there was a significant drop in the homicide rate and the frequency of violence. Intake of fish is also a good remedy for depression. Findings of a research study suggest that fish consumption may be beneficial for women’s mental health and reduces the risk of developing depression in women.
Among the 16 studies comparing the effect of omega-3 PUFA treatment with that of the placebo,33,34,36,47-49,51-53,55-61 the main results revealed a significantly greater association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 16; Hedges g, 0.372; 95% CI, 0.032-0.712; P = .03; eFigure 3 in the Supplement). The meta-analysis of the subgroup focusing on non–placebo-controlled trials also showed a significantly greater association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 3; Hedges g, 0.399; 95% CI, 0.154-0.643; P = .001).35,50,54
Sorgi, P. J., Hallowell, E. M., Hutchins, H. L. & Sears, B. (2007, January 17). Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder. Nutrition Journal 6(16). Retrieved from http://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-6-16
Researchers are taking a hard look at a different sort of balance, this one between possible effects of marine and plant omega-3 fats on prostate cancer. Results from the Health Professionals Follow-up Study and others show that men whose diets are rich in EPA and DHA (mainly from fish and seafood) are less likely to develop advanced prostate cancer than those with low intake of EPA and DHA. (6) At the same time, some-but not all-studies show an increase in prostate cancer and advanced prostate cancer among men with high intakes of ALA (mainly from supplements). However, this effect is inconsistent. In the very large Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, for example, there was no link between ALA intake and early, late, or advanced prostate cancer. (7)
One meta-analysis concluded that omega−3 fatty acid supplementation demonstrated a modest effect for improving ADHD symptoms.[39] A Cochrane review of PUFA (not necessarily omega−3) supplementation found "there is little evidence that PUFA supplementation provides any benefit for the symptoms of ADHD in children and adolescents",[40] while a different review found "insufficient evidence to draw any conclusion about the use of PUFAs for children with specific learning disorders".[41] Another review concluded that the evidence is inconclusive for the use of omega−3 fatty acids in behavior and non-neurodegenerative neuropsychiatric disorders such as ADHD and depression.[42]
Krill oil is a source of omega−3 fatty acids.[116] The effect of krill oil, at a lower dose of EPA + DHA (62.8%), was demonstrated to be similar to that of fish oil on blood lipid levels and markers of inflammation in healthy humans.[117] While not an endangered species, krill are a mainstay of the diets of many ocean-based species including whales, causing environmental and scientific concerns about their sustainability.[118][119][120]
As you likely know (and as I’ve been discussing for years), omega-3 fatty acids have anti-inflammatory properties. They have been studied for the treatment and prevention of many diseases, several of which are related to inflammation, including heart disease, stroke, cancer, and Alzheimer’s disease. They have also been shown to be extraordinarily helpful in preventing and treating other brain conditions such as depression and other psychiatric disorders, attention deficit/hyperactivity disorder (ADHD), and concussions.
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.
So back to fish oil in general. The major fish oil benefits include decreasing the risk of heart disease and stroke while also helping reduce symptoms of depression, hypertension, attention deficit hyperactivity disorder (ADHD), joint pain, arthritis and chronic skin ailments like eczema. (2) Fish oil intake has also been associated with aiding the body in weight loss, fertility, pregnancy and increased energy. Prescription fish oil has even been approved by the FDA to lower unhealthy high triglyceride levels. (3)

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)
We hypothesized that omega-3 PUFAs might have anxiolytic effects in patients with significant anxiety- and fear-related symptoms. However, there have been no systematic reviews of this topic to date. Thus, we examined the anxiolytic effects of omega-3 PUFAs in participants with elevated anxiety symptoms in the results of clinical trials to determine the overall efficacy of omega-3 PUFAs for anxiety symptoms irrespective of diagnosis.
These conversions occur competitively with omega−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. They both utilize the same desaturase and elongase proteins in order to synthesize inflammatory regulatory proteins.[50] The products of both pathways are vital for growth making a balanced diet of omega−3 and omega−6 important to an individual's health.[77] A balanced intake ratio of 1:1 was believed to be ideal in order for proteins to be able to synthesize both pathways sufficiently, but this has been controversial as of recent research.[78]
Researchers are taking a hard look at a different sort of balance, this one between possible effects of marine and plant omega-3 fats on prostate cancer. Results from the Health Professionals Follow-up Study and others show that men whose diets are rich in EPA and DHA (mainly from fish and seafood) are less likely to develop advanced prostate cancer than those with low intake of EPA and DHA. (6) At the same time, some-but not all-studies show an increase in prostate cancer and advanced prostate cancer among men with high intakes of ALA (mainly from supplements). However, this effect is inconsistent. In the very large Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, for example, there was no link between ALA intake and early, late, or advanced prostate cancer. (7)
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.
We are now fortunate to understand how these fats work in combination and in isolation, how they are digested, absorbed and utilised in the body, so we are able to tailor different blends of EPA and DHA according to the health benefits we are seeking to achieve. At Igennus, we have long specialised in the role of the omega-3 fatty acid EPA in clinical nutrition, as a powerful tool in the patient’s ‘toolkit’ for helping to regulate inflammation by restoring several biological markers, known as the omega-6 to omega-3 ratio and AA to EPA ratio. Before we discuss the therapeutic role of EPA in nutritional medicine, here’s a very brief summary of the role of both EPA and DHA in health throughout life.
Good points, Miroslav. Focusing on your 4th point, with so many different formulations on the market that contain various preservatives, only looking at the blood levels of omega-3’s as the flag for increased risk for prostate cancer tends to ignore the fact that certain populations in coastal regions maintain a diet high in omega fish oils and don’t have a marked increase level of prostate cancer, pointing to the fact that another agent may be to blame here.

The European Journal of Neuroscience published a study in 2013 showing that fish oil reversed all anxiety-like and depression-like behavior changes induced in rats. This is an interesting study because it stresses the importance of supplementing with fish oil at “critical periods of brain development.” (10) This is exactly why I recommend giving fish oil to our kids from early on to help them so they won’t develop anxiety or depression later in life.
One meta-analysis concluded that omega−3 fatty acid supplementation demonstrated a modest effect for improving ADHD symptoms.[39] A Cochrane review of PUFA (not necessarily omega−3) supplementation found "there is little evidence that PUFA supplementation provides any benefit for the symptoms of ADHD in children and adolescents",[40] while a different review found "insufficient evidence to draw any conclusion about the use of PUFAs for children with specific learning disorders".[41] Another review concluded that the evidence is inconclusive for the use of omega−3 fatty acids in behavior and non-neurodegenerative neuropsychiatric disorders such as ADHD and depression.[42]
Fish oil has been shown to have a direct electrophysiological effect on the myocardium. Initial experience with animal ischemia models demonstrated that the ventricular fibrillation threshold was increased in both animals fed or infused with omega-3 FA.23,24 This progressed to a demonstration, on a cellular and ion channel level, that omega-3 FA reduce both sodium currents and L-type calcium currents.25–29 It is hypothesized that during ischemia, a reduction in the sodium ion current protects hyperexcitable tissue, and a reduction in the calcium ion current reduces arrhythmogenic depolarizing currents.30
My estimate is that close to 90 percent of fish oils on the market today may contain mercury and pesticide residues plus hydrogenated oils. Of course, this is my opinion based on my own research from visiting different manufacturing plants, interviewing companies, and studying the research and the listed ingredients of typical fish oils. I would stay away from ALL fish oils that do not have antioxidants like astaxanthin, which help stabilize the oil from going rancid. I always look for astaxanthin as part of any high-quality fish oil supplement.

Heterogeneity was examined using the Q statistic and the corresponding P values,41 and the I2 statistic was used to evaluate the proportion of variation resulting from among-study differences. Any possible publication bias was detected with both funnel plots and Egger regression in the main part of the meta-analysis.42 By using Duval and Tweedie’s trim-and-fill test, we adjusted the effect sizes for potential publication bias if there was evidence of publication bias detected by this test in the Comprehensive Meta-analysis statistical software, version 3.43 To investigate the potential confounding effects of any outliers within the recruited studies, sensitivity testing was conducted with the 1-study removal method to detect the potential outliers.44


Jump up ^ Crowe, Francesca L.; Appleby, Paul N.; Travis, Ruth C.; Barnett, Matt; Brasky, Theodore M.; Bueno-de-Mesquita, H. Bas; Chajes, Veronique; Chavarro, Jorge E.; Chirlaque, Maria-Dolores (2014-09-01). "Circulating fatty acids and prostate cancer risk: individual participant meta-analysis of prospective studies". Journal of the National Cancer Institute. 106 (9): dju240. doi:10.1093/jnci/dju240. ISSN 1460-2105. PMC 4188122. PMID 25210201.
Fish oil contamination even among “molecularly distilled” brands and those aimed at children is a widespread problem. One study in California tested 10 common brands and found PCBs — toxic industrial pollutants that have contaminated our oceans — in all of them. Some had 70 times the PCBs of other ones and 240x the toxicity. In another study, researchers tested 13 over-the-counter children’s dietary supplements containing fish oil for PCBs. PCBs were detected in all products. Our family takes algae-derived omega-3 (DHA/EPA) capsules, which are bioequivalent to fish oil capsules. Algae are actually the source where fish get their omega-3 content, so we skip the contaminated middle man (or, fish, in this case) and the neurotoxins that come with them given how polluted our oceans are now. I highly recommend parents do their research on what studies show about fish oil contamination and not just trust the labels, as well as consider algae-derived omega-3 capsules as more healthful bioequivalent to fish oil.
Nielsen, G. L., Faarvang, K. L., Thomsen, B. S., Teglbjaerg, K. L., Jensen, L. T., Hansen, T. M., Lervang, H. H., Schmidt, E. B., Dyerberg, J., and Ernst, E. The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial. Eur J Clin Invest 1992;22(10):687-691. View abstract.
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