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.
Omega AD study, Irving et al. (54) Double-blind, placebo-controlled, randomized 1741 DHA (1.7 g/d) and EPA (0.6 g/d) for 6 mo, then for all subjects (supplementation group and placebo group) Supplementation was associated with positive weight gain and appetite in supplementation group at 6 mo, but not in the placebo group, and for both groups at 12 mo
Gajos G1, Rostoff P, Undas A, et al. Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after pci to modify responsiveness to dual antiplatelet therapy) study. J Am Coll Cardiol. 2010 Apr 20;55(16):1671-8. View abstract.
Marine and freshwater fish oil vary in contents of arachidonic acid, EPA and DHA.[15] The various species range from lean to fatty and their oil content in the tissues has been shown to vary from 0.7% to 15.5%.[16] They also differ in their effects on organ lipids.[15] Studies have revealed that there is no relation between total fish intake or estimated omega−3 fatty acid intake from all fish, and serum omega−3 fatty acid concentrations.[17] Only fatty fish intake, particularly salmonid, and estimated EPA + DHA intake from fatty fish has been observed to be significantly associated with increase in serum EPA + DHA.[17]
Meta-analyses (research that combines and analyzes results of multiple studies) generally suggest that the omega-3s are effective, but the findings are not unanimous because of variability between doses, ratios of EPA to DHA, and other study design issues. The most effective preparations appear to have at least 60% EPA relative to DHA. While DHA is thought to be less effective as an antidepressant, it may have protective effects against suicide. Recent work at Massachusetts General Hospital and Emory University suggests that depressed individuals who are overweight and have elevated inflammatory activity may be particularly good candidates for EPA treatment.
It is also believed that women who do not have a sufficient intake of EPA and DHA in their diet suffer from depression after childbirth, as there is a transfer of some amount of brain mass from the mother to the child in the last stages of pregnancy. Thus, it is very beneficial to consume fish oil either by eating fish or taking fish oil supplements, tablets, capsules, or pills during pregnancy for the overall development of the child and the well-being of the mother. However, it should be noted that fish oil obtained from the liver of the fish, example – cod liver oil, should not be consumed during pregnancy as cod liver oil is high in retinol and vitamin A, which are usually known to cause birth defects.
Metagenics offers a wide range of educational opportunities including webinars, group meetings, and seminars as part of our commitment to continuing functional medicine education. Our goal is to give our practitioners further insight to help address their patients’ unique health needs for a higher level of personalized, lifetime wellness care. We have been sharing this ever-growing body of nutritional and lifestyle research for over 25 years.
I now suspect that those thousands of gel-covered capsules I’ve swallowed over the years may have done little more than enrich the pockets of supplement producers and sellers. A number of extensive analyses have been conducted, some supporting and others refuting the value of fish oils to the cardiovascular system, along with studies of other purported health benefits that also have had mixed results.

Fish oil contains two very important omega-3 PUFAs. I’m talking about docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). DHA and EPA are sometimes called the marine omega-3s because they mainly come from fish. Some of the best fish to eat to obtain fish oil from in your diet include wild-caught salmon, herring, white fish, sardines and anchovies.

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)

Guallar, E., Aro, A., Jimenez, F. J., Martin-Moreno, J. M., Salminen, I., van't Veer, P., Kardinaal, A. F., Gomez-Aracena, J., Martin, B. C., Kohlmeier, L., Kark, J. D., Mazaev, V. P., Ringstad, J., Guillen, J., Riemersma, R. A., Huttunen, J. K., Thamm, M., and Kok, F. J. Omega-3 fatty acids in adipose tissue and risk of myocardial infarction: the EURAMIC study. Arterioscler.Thromb.Vasc.Biol 1999;19(4):1111-1118. View abstract.
If you have a bleeding disorder, bruise easily or take blood-thinning medications, you should use fish oil supplements with extra caution since large doses of omega-3 fatty acids can increase bleeding risk. This bleeding risk also applies to people with no history of bleeding disorders or current medication usage. If you have type 2 diabetes, you should only use fish oil supplements under your doctor’s supervision. Individuals with type 2 diabetes can experience increases in fasting blood sugar levels while taking fish oil supplements.
The number, location, and orientation of the double bonds determine the health effects of fatty acids on the body. One aspect of this is their effect on triglycerides and LDL and HDL types of cholesterol, which in turn affect how much cholesterol gets deposited on the inside of blood vessels. There are also subtypes of LDL and HDL which are also likely important to their health effects.
However, in both observational studies and controlled clinical trials, eating fish was shown to foster optimal development of a baby’s brain and nervous system, prompting advice that pregnant women and nursing mothers eat more fish rich in omega-3s while avoiding species that may contain mercury or other contaminants like PCBs sometimes found in freshwater fish.
Saito, Y., Yokoyama, M., Origasa, H., Matsuzaki, M., Matsuzawa, Y., Ishikawa, Y., Oikawa, S., Sasaki, J., Hishida, H., Itakura, H., Kita, T., Kitabatake, A., Nakaya, N., Sakata, T., Shimada, K., and Shirato, K. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis 2008;200(1):135-140. View abstract.
Added inactive ingredients also contribute to product safety. Eight supplements in this study contained ‘natural’ flavors such as citrus-derived additives. One product, Coromega Omega-3, also contained benzoic acid, a popular antibacterial agent linked to carcinogenic risks when combined with vitamin C. Other controversial excipients included the artificial coloring agents FD&C Blue 1 and FD&C Red 40 as well as the whitening agent titanium dioxide.

“This systematic review did find moderate evidence that ALA, found in plant oils (such as rapeseed or canola oil) and nuts (particularly walnuts) may be slightly protective of some diseases of the heart and circulation. However, the effect is very small, 143 people would need to increase their ALA intake to prevent one person developing arrhythmia. One thousand people would need to increase their ALA intake to prevent one person dying of coronary heart disease or experiencing a cardiovascular event.  ALA is an essential fatty acid, an important part of a balanced diet, and increasing intakes may be slightly beneficial for prevention or treatment of cardiovascular disease."
In lab experiments, animals given krill showed improved navigation skills. What this means is that they achieved higher levels of cognition and memory required to navigate complex territory.28 In addition, research shows that animals supplemented with krill oil showed significantly fewer signs of depression and resignation. This improvement in mood was equivalent to the effect of the prescription anti-depressant drug imipramine (Tofranil®).29
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
Kabir, M., Skurnik, G., Naour, N., Pechtner, V., Meugnier, E., Rome, S., Quignard-Boulange, A., Vidal, H., Slama, G., Clement, K., Guerre-Millo, M., and Rizkalla, S. W. Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am.J.Clin.Nutr. 2007;86(6):1670-1679. View abstract.
The three types of omega−3 fatty acids involved in human physiology are α-linolenic acid (ALA), found in plant oils, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both commonly found in marine oils.[2] Marine algae and phytoplankton are primary sources of omega−3 fatty acids. Common sources of plant oils containing ALA include walnut, edible seeds, clary sage seed oil, algal oil, flaxseed oil, Sacha Inchi oil, Echium oil, and hemp oil, while sources of animal omega−3 fatty acids EPA and DHA include fish, fish oils, eggs from chickens fed EPA and DHA, squid oils, and krill oil. Dietary supplementation with omega−3 fatty acids does not appear to affect the risk of death, cancer or heart disease.[4][5] Furthermore, fish oil supplement studies have failed to support claims of preventing heart attacks or strokes or any vascular disease outcomes.[6][7]
Anxiety, the most commonly experienced psychiatric symptom, is a psychological state derived from inappropriate or exaggerated fear leading to distress or impairment. The lifetime prevalence of any anxiety disorder is reported to be approximately 1 in 3.1 Anxiety is often comorbid with depressive disorders2 and is associated with lower health-related quality of life3 and increased risk of all-cause mortality.4 Treatment options include psychological treatments, such as cognitive-behavioral therapy and pharmacological treatments, mainly with selective serotonin reuptake inhibitors.5 Individuals with anxiety and related disorders tend to be more concerned about the potential adverse effects of pharmacological treatments (eg, sedation or drug dependence) and may be reluctant to engage in psychological treatments that can be time-consuming and costly, as well as sometimes limited in availability.6 Thus, evidence-based and safer treatments are required, especially for anxious patients with comorbid medical conditions.

Dry eye. Some clinical research shows that eating more fish oil is linked to a lower risk of getting dry eye syndrome in women. Other research shows that taking a specific fish oil product (PRN Dry Eye Omega Benefits softgels) daily modestly improves symptoms of dry eye such as pain, blurred vision, and sensitivity. Other research using other forms of fish oil products suggests that taking these supplements for 4-12 weeks modest improves some dry eye symptoms. However, the sensation of eye dryness is not always improved. Other research also shows that taking a specific combination products containing fish oil and other ingredients might improve some dry eye symptoms; however, this research is conflicted and poor quality.


Fish oil therapy is efficacious and safe for patients with severe to moderate hypertriglyceridemia. Combination therapy with HMG-CoA reductase inhibitors is also efficacious and has not been associated with any serious adverse reactions. Fish oil therapy added to fenofibrate in patients with severe hypertriglyceridemia is also effective and safe. Accordingly, it may be a safe and effective adjunct in the pharmacotherapy of the mixed lipid disorder that is frequently encountered in patients with the metabolic syndrome and/or type II diabetes mellitus.
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.

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)
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.

We included 79 RCTs (112,059 participants) in this review update and found that 25 were at low summary risk of bias. Trials were of 12 to 72 months’ duration and included adults at varying cardiovascular risk, mainly in high‐income countries. Most studies assessed LCn3 supplementation with capsules, but some used LCn3‐ or ALA‐rich or enriched foods or dietary advice compared to placebo or usual diet.
In your final paragraph, you suggest that a ratio of 2:1 EPA/DHA maybe best for reducing inflammation. Are you suggesting using two separate products to obtain that ratio? I can't see how it is achieveable through standard omega-3 products. Good fish oil brands are typically 60% or higher EPA, but never reach a 2:1 ratio in my product searches. According to case studies (link below), 1 gram of EPA per day (60% or more of the total omega-3 content) is sufficient and the highest efficacy.

Krauss-Etschmann, S., Hartl, D., Rzehak, P., Heinrich, J., Shadid, R., Del, Carmen Ramirez-Tortosa, Campoy, C., Pardillo, S., Schendel, D. J., Decsi, T., Demmelmair, H., and Koletzko, B. V. Decreased cord blood IL-4, IL-13, and CCR4 and increased TGF-beta levels after fish oil supplementation of pregnant women. J.Allergy Clin.Immunol. 2008;121(2):464-470. View abstract.


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
Wright, S. A., O'Prey, F. M., McHenry, M. T., Leahey, W. J., Devine, A. B., Duffy, E. M., Johnston, D. G., Finch, M. B., Bell, A. L., and McVeigh, G. E. A randomised interventional trial of omega-3-polyunsaturated fatty acids on endothelial function and disease activity in systemic lupus erythematosus. Ann.Rheum.Dis. 2008;67(6):841-848. View abstract.
Recently another Omega-3 fatty acid, DPA (Docosapentaenoic Acid) has been discussed more frequently in the scientific community, as a new and very potent Omega-3 fatty acid. Previously thought to work in through EPA and DHA we are now learning it has very distinct functions in the body. All three of these polyunsaturated fats play an important role in the functioning of our bodies.
Hamazaki, K., Itomura, M., Huan, M., Nishizawa, H., Sawazaki, S., Tanouchi, M., Watanabe, S., Hamazaki, T., Terasawa, K., and Yazawa, K. Effect of omega-3 fatty acid-containing phospholipids on blood catecholamine concentrations in healthy volunteers: a randomized, placebo-controlled, double-blind trial. Nutrition 2005;21(6):705-710. View abstract.
Human diet has changed rapidly in recent centuries resulting in a reported increased diet of omega−6 in comparison to omega−3.[83] The rapid evolution of human diet away from a 1:1 omega−3 and omega−6 ratio, such as during the Neolithic Agricultural Revolution, has presumably been too fast for humans to have adapted to biological profiles adept at balancing omega−3 and omega−6 ratios of 1:1.[84] This is commonly believed to be the reason why modern diets are correlated with many inflammatory disorders.[83] While omega−3 polyunsaturated fatty acids may be beneficial in preventing heart disease in humans, the level of omega−6 polyunsaturated fatty acids (and, therefore, the ratio) does not matter.[78][85]
EPA and DHA are vital nutrients and may be taken to maintain healthy function of the following: brain and retina: DHA is a building block of tissue in the brain and retina of the eye. It helps with forming neural transmitters, such as phosphatidylserine, which is important for brain function. DHA is found in the retina of the eye and taking DHA may be necessary for maintaining healthy levels of DHA for normal eye function.
One reason omega-3 fatty acids may be so beneficial to this many aspects of health could be that they help decrease system-wide inflammation. (49, 50, 51, 52, 53) Inflammation is at the root of most diseases and is related to the development of nearly every major illness, so by eating a nutrient-dense, anti-inflammatory diet, you give your body its best chance to fight disease like it was designed to do.
The strongest evidence for a beneficial effect of omega-3 fats has to do with heart disease. These fats appear to help the heart beat at a steady clip and not veer into a dangerous or potentially fatal erratic rhythm. (1) Such arrhythmias cause most of the 500,000-plus cardiac deaths that occur each year in the United States. Omega-3 fats also lower blood pressure and heart rate, improve blood vessel function, and, at higher doses, lower triglycerides and may ease inflammation, which plays a role in the development of atherosclerosis. (1)
Omega−3 fatty acids are formed in the chloroplasts of green leaves and algae. While seaweeds and algae are the source of omega−3 fatty acids present in fish, grass is the source of omega−3 fatty acids present in grass fed animals.[134] When cattle are taken off omega−3 fatty acid rich grass and shipped to a feedlot to be fattened on omega−3 fatty acid deficient grain, they begin losing their store of this beneficial fat. Each day that an animal spends in the feedlot, the amount of omega−3 fatty acids in its meat is diminished.[135]

Today, some doctors are starting to measure the omega-3 index levels of their patients, just like they do with cholesterol levels. However, if your doctor does not offer this, several companies provide a quick and easy blood test you can conduct yourself, including OmegaQuant. This company is run by by Dr. William Harris, one of the scientists who initially developed the concept of the omega-3 index.
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).
Boucher, O., Burden, M. J., Muckle, G., Saint-Amour, D., Ayotte, P., Dewailly, E. ... Jacobson, J. L.. (2011, May). Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age. American Journal of Clinical Nutrition 93(5), 1025-1037. Retrieved from http://ajcn.nutrition.org/content/93/5/1025.full
Our scientists also focused on each oil’s freshness, measured by the degree of oxidation. Oxidation occurs in two phases: primary (measured by peroxide values) and secondary (measured by p-anisidine values). Total oxidation is formalized into a quantitative score, TOTOX. While Labdoor conducted tests of both primary and secondary oxidation, advances in rancidity testing confirm that added flavors–particularly added citrus flavors prevalent in liquid formulations–skew p-anisidine values and result in false positive outcomes. Until analytical techniques measuring p-anisidine values that are able to account for added flavors are established, Labdoor will use peroxide values as the primary indicator of freshness. All products recorded measurable levels of oxidation, with the average product recording a peroxide values of 3.7 meq/kg. 14/51 products recorded peroxide levels at or above the upper limit (10 meq/kg).
As mentioned above, the omega-3 index has been suggested as a predictor of the risk of coronary heart disease and other cardiovascular events. One study on a population in Seattle found that people with low omega-3 index levels were 10 times as likely to die from sudden cardiac death compared to people with higher omega-3 index levels (13). The NIH-funded Framingham study referenced above showed that the people with the highest omega-3 index levels had a 33% reduction in risk of death from any cause compared to the people with the lowest levels (2). In addition, a new study focused on individuals age 25 to 41 found that higher omega-3 index levels were associated with lower blood pressure in healthy adults (14).
Khandelwal, S., Demonty, I., Jeemon, P., Lakshmy, R., Mukherjee, R., Gupta, R., Snehi, U., Niveditha, D., Singh, Y., van der Knaap, H. C., Passi, S. J., Prabhakaran, D., and Reddy, K. S. Independent and interactive effects of plant sterols and fish oil n-3 long-chain polyunsaturated fatty acids on the plasma lipid profile of mildly hyperlipidaemic Indian adults. Br.J.Nutr. 2009;102(5):722-732. View abstract.
Recent studies have shown that the consumption of fish oil (or, more specifically, the omega-3 fatty acids found in fish oil) can improve fertility in both men and women. DHA, which is a byproduct of omega-3 fatty acids, plays a key role in the mobility of sperm and health of sperm in men. Low blood levels of DHA have been linked to decreased fertility. Animal studies have found that the DHA in fish is vital to changing dysfunctional round-headed sperm into strong swimmers with cone-shaped heads packed with egg-opening proteins. (29)
However, since the dosage of fish oil required for an ideal effect in the improvement of a patient is unknown, the Arthritis Center in the Department of Rheumatology at John Hopkins University considers including omega-3 fatty acids and fish oil in the treatment of arthritis as controversial. The University also cautions that arthritis patients must be wary of all the other side effects that can come from using fish oil. You can read more about arthritis on the web page of the Arthritis Foundation and the Arthritis Center.
Respected health care organizations proposed intake recommendations for oily fish of two servings per week for healthy adults, which equates to approximately a daily total of 500 milligrams (mg) EPA and DHA.‡ The recommendation encourages adults already with or at-risk of developing cardiovascular disease to talk to their primary healthcare professional about supplementing with amounts greater than 500 mg of EPA and DHA per day. Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease.
Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.
For preventing and reversing the progression of hardening of the arteries after angioplasty: 6 grams of fish oil daily starting one month before angioplasty and continuing for one months after, followed by 3 grams daily for 6 months thereafter has been used. Also, 15 grams of fish oil has been taken daily for 3 weeks before angioplasty and for 6 months thereafter.
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