Stiefel, P., Ruiz-Gutierrez, V., Gajon, E., Acosta, D., Garcia-Donas, M. A., Madrazo, J., Villar, J., and Carneado, J. Sodium transport kinetics, cell membrane lipid composition, neural conduction and metabolic control in type 1 diabetic patients. Changes after a low-dose n-3 fatty acid dietary intervention. Ann Nutr Metab 1999;43(2):113-120. View abstract.
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.

EPA and DHA  stand for eicosapentaenoic acid and docosahexaenoic acid respectively. These fatty acids are omega-3 fats, which are found in cold water fish. EPA DHA are highly unsaturated fats because they contain six and five double bonds on their long structural chains. These polyunsaturated fats play a very important role with the function of our bodies.
Smithers, L. G., Collins, C. T., Simmonds, L. A., Gibson, R. A., McPhee, A., and Makrides, M. Feeding preterm infants milk with a higher dose of docosahexaenoic acid than that used in current practice does not influence language or behavior in early childhood: a follow-up study of a randomized controlled trial. Am J Clin Nutr 2010;91(3):628-634. View abstract.
Cardiovascular disease is the cause of 38% of all deaths in the United States, many of which are preventable (28). Chronic inflammation is thought to be the cause of many chronic diseases, including cardiovascular disease (29). EPA and DHA are thought to have antiinflammatory effects and a role in oxidative stress (30) and to improve cellular function through changes in gene expression (31). In a study that used human blood samples, EPA+DHA intake changed the expression of 1040 genes and resulted in a decreased expression of genes involved in inflammatory and atherogenesis-related pathways, such as nuclear transcription factor κB signaling, eicosanoid synthesis, scavenger receptor activity, adipogenesis, and hypoxia signaling (31). Circulating markers of inflammation, such as C-reactive protein (CRP), TNF α, and some ILs (IL-6, IL-1), correlate with an increased probability of experiencing a cardiovascular event (32). Inflammatory markers such as IL-6 trigger CRP to be synthesized by the liver, and elevated levels of CRP are associated with an increased risk of the development of cardiovascular disease (33). A study of 89 patients showed that those treated with EPA+DHA had a significant reduction in high-sensitivity CRP (66.7%, P < 0.01) (33). The same study also showed a significant reduction in heat shock protein 27 antibody titers (57.69%, P < 0.05), which have been shown to be overexpressed in heart muscle cells after a return of blood flow after a period of ischemia (ischemia-reperfusion injury) and may potentially have a cardioprotective effect (33).
As a result, we depend on our diet to get the necessary Omega-3 fatty acids into our bodies. These two fatty acids work together in human health. DHA helps with cell membrane structure and assists in normal growth and development. While both EPA and DHA participate in key pathways of the immune system where they control key processes that support our health. Together they provide a number of important health benefits throughout our lifetime.
From the time of your pregnancy through your child's later life, omega-3 fats DHA and EPA have a radically important role in her brain health and other functions. I recommend supplementing with krill oil before and during pregnancy, and while you breastfeed. Babies receive DHA through your breast milk, so continuing breastfeeding through the first year will give your child a great headstart for health and success.
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
Five studies with 7 data sets recruited participants without specific clinical conditions.36,47,51,55,60 The main results revealed that there was no significant difference in the association of treatment with reduced anxiety symptoms between patients receiving omega-3 PUFA treatment and those not receiving it (k, 5; Hedges g, –0.008; 95% CI, –0.266 to 0.250; P = .95) (Figure 3A). Fourteen studies with 14 data sets recruited participants with specific clinical diagnoses.33-35,48-50,52-54,56-59,61 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, 14; Hedges g, 0.512; 95% CI, 0.119-0.906; P = .01) (Figure 3A). Furthermore, according to the interaction test, the association of omega-3 PUFA treatment with reduced anxiety symptoms was significantly stronger in subgroups with specific clinical diagnoses than in subgroups without specific clinical conditions (P = .03).
A six week, double-blind study on fish oil supplementation for body composition showed that the group taking 4 grams/day of fish oil (contained 1600mg if EPA & 800mg of DHA) experienced a significant increase in lean body mass and significant decrease in fat mass compared to a group that took safflower oil (an omega-6 oil). The fish oil group also saw a tendency for decreases in cortisol, a hormone associated with belly fat gain when elevated.
Gerber, J. G., Kitch, D. W., Fichtenbaum, C. J., Zackin, R. A., Charles, S., Hogg, E., Acosta, E. P., Connick, E., Wohl, D., Kojic, E. M., Benson, C. A., and Aberg, J. A. Fish oil and fenofibrate for the treatment of hypertriglyceridemia in HIV-infected subjects on antiretroviral therapy: results of ACTG A5186. J.Acquir.Immune.Defic.Syndr. 4-1-2008;47(4):459-466. View abstract.
First difference is in the area of omega-6 fatty acid metabolism. Whereas EPA is the inhibitor of the enzyme (D5D) that directly produces AA, DHA is an inhibitor of another key enzyme delta-6-desaturase (D6D) that produces the first metabolite from linoleic acid known as gamma linolenic acid or GLA (6). However, this is not exactly an advantage. Even though reduction of GLA will eventually decrease AA production, it also has the more immediate effect of reducing the production of the next metabolite known as dihomo gamma linolenic acid or DGLA. This can be a disaster as a great number of powerful anti-inflammatory eicosanoids are derived from DGLA. This is why if you use high-dose DHA it is essential to add back trace amounts of GLA to maintain sufficient levels of DGLA to continue to produce anti-inflammatory eicosanoids.
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To reach the required dose of EPA for treating certain conditions such as depression, CVD or CFS/ME you would need to take approximately 1-2 grams of ‘free EPA’ daily. Even with a concentrated omega-3 fish oil supplement, offering 180 mg excess EPA over DHA, this would require 10-20 capsules daily – significant in terms of volume and cost, and not efficient in terms of uptake in the body as our capacity for fat absorption is limited. The most effective and efficient way to ensure high EPA uptake in the body rapidly is to supplement with pure EPA for a minimum of 3-6 months.


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.

The evidence that fish oil consumption should be used for primary prevention of CAD is based on observational studies. The only randomized trial for primary prevention, the JELIS trial, showed a moderate relative risk reduction and was conducted in a very specific group. Nevertheless, to date, there has been no strong signal suggesting any serious adverse effects of having high DHA and EPA oils in the diet. We agree with the national guidelines that one should consume moderate amounts of fish oil— either in supplement or through the dietary intake of fatty fish with low mercury levels.
Omega−3 fatty acids are important for normal metabolism.[8] Mammals are unable to synthesize omega−3 fatty acids, but can obtain the shorter-chain omega−3 fatty acid ALA (18 carbons and 3 double bonds) through diet and use it to form the more important long-chain omega−3 fatty acids, EPA (20 carbons and 5 double bonds) and then from EPA, the most crucial, DHA (22 carbons and 6 double bonds).[8] The ability to make the longer-chain omega−3 fatty acids from ALA may be impaired in aging.[9][10] In foods exposed to air, unsaturated fatty acids are vulnerable to oxidation and rancidity.[11]
The evidence that fish oil consumption should be used for primary prevention of CAD is based on observational studies. The only randomized trial for primary prevention, the JELIS trial, showed a moderate relative risk reduction and was conducted in a very specific group. Nevertheless, to date, there has been no strong signal suggesting any serious adverse effects of having high DHA and EPA oils in the diet. We agree with the national guidelines that one should consume moderate amounts of fish oil— either in supplement or through the dietary intake of fatty fish with low mercury levels.
In fact, dietary fat intake has been among the most widely studied dietary risk factors for breast and prostate cancers. Two studies from 2002 explain how omega-3 can protect against breast cancer. BRCA1 (breast cancer gene 1) and BRCA2 (breast cancer gene 2) are two tumor suppressor genes that, when functioning normally, help repair DNA damage, a process that also prevents tumor development.
Thank you for your kind comment. As pointed out above, the main limitation of our meta-analysis is the heterogeneity, which we address several times in our main manuscript. We included studies with several different situations and participants with different underlying diseases, which would also result in wide heterogeneity in our meta-analysis. Based upon our post-hoc analysis, there was some common characteristics among the six trials with nominally significant results, including specific clinical diagnoses (5/6) and, placebo-control (4/6), which had also previously been addressed in our subgroup meta-analysis. Therefore, we suggested future placebo-controlled trials investigating the treatment effect of omega-3 in participants with specific clinical diagnoses should be warranted. In addition, improving underlying specific clinical diagnoses (5/6), good quality (placebo-control (4/6), low drop-out rate (zero in Exp/control groups: 4/6)), and long treatment duration (>= 12 weeks: 4/6) are all good indicators of high quality.
Omega-3 fatty acids get a fair amount of time in the press and a great deal of respect at this point. But do you know what omega-3s are? What omega-3 benefits could convince you to add more oily fish (or maybe a supplement) to your diet? Are omega-3 foods really that big of a deal when it comes to eating a nutrient-dense diet? Could you be deficient in these fatty acids?

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]
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).
Results of studies investigating the role of LCPUFA supplementation and LCPUFA status in the prevention and therapy of atopic diseases (allergic rhinoconjunctivitis, atopic dermatitis and allergic asthma) are controversial; therefore, at the present stage of our knowledge (as of 2013) we cannot state either that the nutritional intake of n−3 fatty acids has a clear preventive or therapeutic role, or that the intake of n-6 fatty acids has a promoting role in context of atopic diseases.[64]
The deficiency of EPA and DHA in diet contributes to skin conditions, such as dandruff, thinning hair, eczema and psoriasis, as well as age spots and sun spots. Without the essential fatty acids, too much moisture leaves the skin. The truth is your internal health can appear on your skin, and taking fish oil internally as a supplement may be as good as or better than applying conventional moisturizers.
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.
If you’ve been paying attention to health headlines over the last few decades, you’ve likely heard about essential fatty acids (EFAs) — specifically omega-3s and omega-6s. These nutrients play many vital roles in supporting our overall health, including increasing nutrient absorption, ensuring proper growth and development of the brain and nervous system, and reducing the risk of chronic illnesses, such as heart disease.  Click here for a guide to understanding omega-3 and omega-6 fatty acids and how they influence your health.

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.
Sangiovanni, J. P., Agron, E., Meleth, A. D., Reed, G. F., Sperduto, R. D., Clemons, T. E., and Chew, E. Y. {omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study. Am J Clin Nutr 2009;90(6):1601-1607. View abstract.
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.
Increasing ALA intake probably makes little or no difference to all‐cause mortality (RR 1.01, 95% CI 0.84 to 1.20, 19,327 participants; 459 deaths, 5 RCTs),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25, 18,619 participants; 219 cardiovascular deaths, 4 RCTs), and it may make little or no difference to CHD events (RR 1.00, 95% CI 0.80 to 1.22, 19,061 participants, 397 CHD events, 4 RCTs, low‐quality evidence). However, increased ALA may slightly reduce risk of cardiovascular events (from 4.8% to 4.7%, RR 0.95, 95% CI 0.83 to 1.07, 19,327 participants; 884 CVD events, 5 RCTs, low‐quality evidence), and probably reduces risk of CHD mortality (1.1% to 1.0%, RR 0.95, 95% CI 0.72 to 1.26, 18,353 participants; 193 CHD deaths, 3 RCTs), and arrhythmia (3.3% to 2.6%, RR 0.79, 95% CI 0.57 to 1.10, 4,837 participants; 141 events, 1 RCT). Effects on stroke are unclear.
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)
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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