LCn3s are long chain fatty acids from fish, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ALA is plant-based omega 3-alpha‐linolenic acid. Fatty acids are essentially chains of carbon atoms with an OOH group at one end. The available binding sites on the carbon atoms are filled with hydrogen atoms. If every binding site is occupied with a hydrogen, that is a saturated fatty acid. If instead of hydrogen atoms there is a double bond between two adjacent carbon atoms, that is an unsaturated fatty acid. If there are multiple double bonds, that is polyunsaturated. Omega 3 fatty acids are unsaturated, with a double bond between the third and fourth carbon atoms from the end opposite the OOH group.
"Fish is still the mainstay of the diet in many parts of the world where there is very little heart disease," he says. "I think when you replace higher fat foods and highly processed foods with fish there is going to be some benefit.'' So it may be that by substituting fish for red meats, bacon and luncheon meats, and similar high-fat foods, you are making a change that will lead to improving your health outcomes, he says.
What makes omega-3 fats special? They are an integral part of cell membranes throughout the body and affect the function of the cell receptors in these membranes. They provide the starting point for making hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. They also bind to receptors in cells that regulate genetic function. Likely due to these effects, omega-3 fats have been shown to help prevent heart disease and stroke, may help control lupus, eczema, and rheumatoid arthritis, and may play protective roles in cancer and other conditions.
Fish oil supplement studies have failed to support claims of preventing heart attacks or strokes.[3][4][5][6] Earlier, in 2007, the American Heart Association had recommended the consumption of 1 gram of fish oil daily, preferably by eating fish, for patients with coronary artery disease, but cautioned pregnant and nursing women to avoid eating fish with high potential for mercury contaminants including mackerel, shark, and swordfish.[32] (Optimal dosage was related to body weight.)
Carrero, J. J., Fonolla, J., Marti, J. L., Jimenez, J., Boza, J. J., and Lopez-Huertas, E. Intake of fish oil, oleic acid, folic acid, and vitamins B-6 and E for 1 year decreases plasma C-reactive protein and reduces coronary heart disease risk factors in male patients in a cardiac rehabilitation program. J.Nutr. 2007;137(2):384-390. View abstract.
Fish Oil capsules contain omega-3 polyunsaturated fatty acids. Omega-3 polyunsaturated fatty acids are found in oils from certain types of fish, vegetables, and other plant sources. These fatty acids are not made by the body and must be consumed in the diet. Omega-3 polyunsaturated fatty acids work by lowering the body's production of triglycerides. High levels of triglycerides can lead to coronary artery disease, heart disease, and stroke.

There was a significantly greater association of treatment with reduced anxiety symptoms in participants receiving omega-3 PUFAs than in those not receiving omega-3 PUFAs in the subgroup with an EPA percentage less than 60% (k, 11; Hedges g, 0.485; 95% CI, 0.017-0.954; P = .04; Figure 4)35,49,52,54-61 but no significant difference in the association of treatment with reduced anxiety symptoms between participants receiving omega-3 PUFAs and those not receiving omega-3 PUFAs in the subgroup with an EPA percentage of at least 60% (k, 9; Hedges g, 0.092; 95% CI, –0.102 to 0.285; P = .35) (Figure 4).33,34,36,47,48,50,51,53,60 There were no significantly different estimated effect sizes between these 2 subgroups by the interaction test (P = .13).

According to research conducted at Harvard University, omega-3 fatty acid deficiency is officially one of the top 10 causes of death in America, claiming the lives of up to 96,000 people each year. Out of the 12 dietary, lifestyle and metabolic risk factors examined in the study, omega-3 fatty acid deficiency ranked as the sixth highest killer of Americans. (1) These deaths are considered preventable since getting enough omega 3-fatty acids in your diet can ward off this now common cause of death, and fish oil benefits omega-3 intake as a potent omega-3 source.


Most people get far too little omega-3s in their diet. In fact, research consistently indicates that the majority of Americans have just slightly more than half the amount of EPA and DHA in their tissues than they need for optimum brain and body health. This is partly due to a high dietary intake of unhealthy fats combined with an inadequate intake of EPA and DHA.
Under these conditions, it may make sense to try fish oil even at higher doses than what I recommended. There is some evidence that krill oil will get the omega-3 fatty acids better into the brain in the psychiatric conditions that I listed. And there is some evidence that EPA-rich fish oils are better than DHA-rich fish oils for some of those psychiatric conditions as well. So there’s room to play around with the different possibilities if those things apply to you. But for the average case, limit the fish oil to 250 milligrams of EPA and DHA combined when you take it, but in all cases, go for food first, and go for fish oil only after you have exhausted those possibilities.

Jump up ^ Siscovick DS, Barringer TA, Fretts AM, Wu JH, Lichtenstein AH, Costello RB, Kris-Etherton PM, Jacobson TA, Engler MB, Alger HM, Appel LJ, Mozaffarian D (2017). "Omega−3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association". Circulation. 135 (15): e867–84. doi:10.1161/CIR.0000000000000482. PMID 28289069.


DHA is especially vital for infant and child brain and nervous system development, as well as visual function. In older children, high DHA levels have been shown to improve learning ability, while deficiencies have been linked to learning problems and ADHD. And in adults, some studies have shown that DHA helps protect against cognitive decline and Alzheimer’s disease.
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.

Several large trials have evaluated the effect of fish or fish oils on heart disease. In the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardio (known as the GISSI Prevention Trial), heart attack survivors who took a 1-gram capsule of omega-3 fats every day for three years were less likely to have a repeat heart attack, stroke, or die of sudden death than those who took a placebo. (2) Notably, the risk of sudden cardiac death was reduced by about 50 percent. In the more recent Japan EPA Lipid Intervention Study (JELIS), participants who took EPA plus a cholesterol-lowering statin were less likely to have a major coronary event (sudden cardiac death, fatal or nonfatal heart attack, unstable angina, or a procedure to open or bypass a narrowed or blocked coronary artery) than those who took a statin alone. (3)

DHA is vital for early brain development and maintenance, while EPA seems to be closely related to behavior and mood. Together, both molecules provide critical neuroprotective benefits.11 These neuroprotective effects are important for the prevention of age-related brain shrinkage (cortical atrophy). Aging adults with brain shrinkage often experience memory loss, cognitive decline, and an increase in depression.12-14
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The conversion of ALA to EPA and further to DHA in humans has been reported to be limited, but varies with individuals.[79][80] Women have higher ALA-to-DHA conversion efficiency than men, which is presumed[81] to be due to the lower rate of use of dietary ALA for beta-oxidation. One preliminary study showed that EPA can be increased by lowering the amount of dietary linoleic acid, and DHA can be increased by elevating intake of dietary ALA.[82]
There are three types of omega-3 fatty acids, which include EPA, DHA and ALA, which is alpha-linoleic acid. Although EPA and DHA are found to have high amounts from animal sources, ALA is found in rich concentrations in plant sources, including certain vegetable oils and flaxseeds, although fatty fish and shellfish are the best sources of EPA and DHA, according to the National Center for Complementary and Alternative Medicine. Examples of these fatty fish and shellfish include salmon, tuna, trout, crab, oysters and mussels.

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]
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.
Krauss-Etschmann et al. (26) Double-blind, placebo-controlled, randomized 311 DHA+EPA daily with either fish oil with DHA (0.5 g) and EPA (0.15 g) or with methyltetrahydrofolic acid (400 μg), both, or placebo, from gestation week 22 Fish-oil supplementation was associated with decreased levels of maternal inflammatory/TH1 cytokines and a decrease of fetal Th2-related cytokines
Birch, E. E., Carlson, S. E., Hoffman, D. R., Fitzgerald-Gustafson, K. M., Fu, V. L., Drover, J. R., Castaneda, Y. S., Minns, L., Wheaton, D. K., Mundy, D., Marunycz, J., and Diersen-Schade, D. A. The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Am J Clin Nutr 2010;91(4):848-859. View abstract.
There is, however, significant difficulty in interpreting the literature due to participant recall and systematic differences in diets.[53] There is also controversy as to the efficacy of omega−3, with many meta-analysis papers finding heterogeneity among results which can be explained mostly by publication bias.[54][55] A significant correlation between shorter treatment trials was associated with increased omega−3 efficacy for treating depressed symptoms further implicating bias in publication.[55]
People used to believe that osteoporosis and osteoarthritis were the result of aging and reduced intake of calcium and milk products. Science has now shown that these bone and joint disorders are, in part, due to inflammation. Because of this, bones and joints are prime targets for the anti-inflammatory properties of omega-3 oils from both fish and krill.
Gorjao, R., Verlengia, R., Lima, T. M., Soriano, F. G., Boaventura, M. F., Kanunfre, C. C., Peres, C. M., Sampaio, S. C., Otton, R., Folador, A., Martins, E. F., Curi, T. C., Portiolli, E. P., Newsholme, P., and Curi, R. Effect of docosahexaenoic acid-rich fish oil supplementation on human leukocyte function. Clin Nutr 2006;25(6):923-938. View abstract.
The Lyon Diet Heart Study, performed shortly after the DART study, was a prospective trial of 607 survivors of MI who were randomized to either a Mediterranean diet or a regular Western diet.49 At a mean follow-up of 27 months, the primary end point of death from cardiovascular causes and nonfatal deaths had a 73% relative risk reduction—a positive effect that continued at follow up assessment at a mean of 46 months.50 FA analysis of plasma lipids showed that in the patients randomized to a Mediterranean diet, there was a higher concentration of alpha-linolenic acid as well as EPA. Fish, however, was consumed in similar amounts by both the Western and Mediterranean diet groups. The higher blood level of EPA in the Mediterranean diet arm was attributed to its synthesis from alpha-linolenic acid, which was 60-times higher than the plasma concentration of EPA. In addition, the risk reduction that occurred in this trial could not be attributed to one particular diet intervention because as the consumption of fruits and vegetables increased, the consumption of monounsaturated fat increased, while saturated fat and cholesterol were decreased.
A certain kidney disease called IgA nephropathy. Some research shows that long-term but not short-term use of fish oil can slow the loss of kidney function in high-risk patients with IgA nephropathy. Fish oil might have greater effects when taken at higher doses. Also, it might be most effective in people with IgA nephropathy who have higher levels of protein in the urine.
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