To exclude the possible confounding effects of clinical variables on the Hedges g, metaregression analysis was conducted with an unrestricted maximum likelihood random-effects model of single variables when there were more than 10 data sets available. Specifically, the clinical variables of interest included mean age, female proportion, sample size, mean body mass index, daily omega-3 PUFA dosage, EPA to DHA ratio, treatment duration, dropout rate, and others. In addition, a subgroup meta-analysis was conducted to investigate potential sources of heterogeneity, specifically, a further subgroup meta-analysis focused on those trials that were placebo controlled or non–placebo controlled. To more clearly uncover the differences in the meta-analysis results among the recruited studies, a further subgroup meta-analysis was performed according to the presence of a specific clinical diagnosis or no specific clinical condition, mean omega-3 PUFA daily dosage, and mean age. In addition, in a previous study, the EPA percentage (ie, ≥60%) in the PUFA regimens had different effects on depression treatment.9 Therefore, we also arranged the subgroup meta-analysis based on the EPA percentage. Furthermore, we arranged subgroup meta-analysis procedures only when there were at least 3 data sets included.45 To investigate the potentially different estimated effect sizes between subgroups, we performed an interaction test and calculated the corresponding P values.46

Most U.S. adults fail to consume adequate amounts of foods rich in EPA and DHA on a regular basis (at least 8 ounces of fatty fish per week is recommended), and probably consume too many omega-6 fats in comparison (soybean oil, canola oil, cottonseed oil, etc.). This omega-3:omega-6 imbalance can have a negative effect on inflammation patterns and may also be implicated as a contributing factor to other processes related to cellular metabolism, hormone signaling, and even weight regulation.
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).
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.
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.
Fish or seafood allergy: Some people who are allergic to seafood such as fish might also be allergic to fish oil supplements. There is no reliable information showing how likely people with seafood allergy are to have an allergic reaction to fish oil. Until more is known, advise patients allergic to seafood to avoid or use fish oil supplements cautiously.
First, all Omega-3 products are not alike. Here's what I learned about Omega-3 from my research. The "3" relates to three sources of Omega-3 fatty acids. Two of them, DHA and EPA are found in marine products such as fish and krill. The third source, ALA, is from plants. So with fish oil you are getting two of the three sources at once. That makes sense to me as a good reason to take Omega-3 fish oil. You will also note below that many of the reasons we choose to take Omega-3 do not occur with plant-based products.

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!

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]


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Fatty predatory fish like sharks, swordfish, tilefish, and albacore tuna may be high in omega-3 fatty acids, but due to their position at the top of the food chain, these species may also accumulate toxic substances through biomagnification. For this reason, the United States Environmental Protection Agency recommends limiting consumption (especially for women of childbearing age) of certain (predatory) fish species (e.g. albacore tuna, shark, king mackerel, tilefish and swordfish) due to high levels of the toxic contaminant mercury. Dioxin, PCBs and chlordane are also present.[13] Fish oil is used as a component in aquaculture feed. More than 50 percent of the world's fish oil used in aquaculture feed is fed to farmed salmon.[14]
Ozaydin, M., Erdogan, D., Tayyar, S., Uysal, B. A., Dogan, A., Icli, A., Ozkan, E., Varol, E., Turker, Y., and Arslan, A. N-3 polyunsaturated fatty acids administration does not reduce the recurrence rates of atrial fibrillation and inflammation after electrical cardioversion: a prospective randomized study. Anadolu.Kardiyol.Derg. 2011;11(4):305-309. View abstract.

The competition between EPA and DHA during digestion and absorption and the fact that DHA appears to ‘block’ the therapeutic actions of EPA can therefore be an issue if we are looking to optimise the benefits associated with EPA (Martins 2009; Bloch & Qawasmi et al, 2011; Sublette et al, 2011). High dose, high concentration and high ratio EPA supplements increase the effectiveness in depression studies, and pure EPA-only is optimal. Depression is also a condition with an inflammatory basis, so this is likely another significant reason for EPA being the key player – its antagonistic relationship with the inflammatory omega-3 AA (arachidonic acid) is very effective at reducing inflammation.
Scaly, itchy skin (eczema). Fish oil might help PREVENT eczema, but research is not consistent. Some early research suggests that mothers who take fish oil supplements during pregnancy reduce the risk of severe eczema in their infants. Also, population research suggests that children who eat fish at least once weekly from 1 to 2 years of age have a lower risk of developing eczema. But other research, including recent studies, suggests that neither supplementation during pregnancy nor supplementation during infancy reduces the risk of eczema. Overall, research suggests that fish oil does not help TREAT eczema once it has developed.
Schilling, J., Vranjes, N., Fierz, W., Joller, H., Gyurech, D., Ludwig, E., Marathias, K., and Geroulanos, S. Clinical outcome and immunology of postoperative arginine, omega-3 fatty acids, and nucleotide-enriched enteral feeding: a randomized prospective comparison with standard enteral and low calorie/low fat i.v. solutions. Nutrition 1996;12(6):423-429. View abstract.
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)

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

Irish AB, Viecelli AK, Hawley CM, et al; Omega-3 Fatty Acids (Fish Oils) and Aspirin in Vascular Access Outcomes in Renal Disease (FAVOURED) Study Collaborative Group. Effect of fish oil supplementation and aspirin use on arteriovenous fistula failure in patients requiring hemodialysis: A randomized clinical trial. JAMA Intern Med. 2017;177(2):184-193. View abstract.
A study in 2013, (Stafford, Jackson, Mayo-Wilson, Morrison, Kendall), stated the following in its conclusion: "Although evidence of benefits for any specific intervention is not conclusive, these findings suggest that it might be possible to delay or prevent transition to psychosis. Further research should be undertaken to establish conclusively the potential for benefit of psychological interventions in the treatment of people at high risk of psychosis."`[56]

Heart disease. Research suggests that eating fish can be effective for keeping people with healthy hearts free of heart disease. People who already have heart disease might also be able to lower their risk of dying from heart disease by eating fish. The picture is less clear for fish oil supplements. For people who already take heart medications such as a "statin" and those who already eat a decent amount of fish, adding on fish oil might not offer any additional benefit.
Jump up ^ Bloch MH, Qawasmi A (October 2011). "Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis". Journal of the American Academy of Child and Adolescent Psychiatry. 50 (10): 991–1000. doi:10.1016/j.jaac.2011.06.008. PMC 3625948. PMID 21961774.
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.

It is well known that fish oil has the ability to improve vision. It also helps in avoiding age-related macular degeneration. The National Eye Institute at the National Institute of Health in the United States plans to conduct a nationwide study to evaluate the effect of fish oil in treating macular degeneration. This study will provide strong scientific evidence regarding the benefits of fish oil for eye care, thereby allowing government agencies and physicians to strongly recommend fish oil for macular degeneration.
Those foods provide enormous amounts of other nutrients that are good for you. nSo it is way better to eat those foods than to take fish oil. With that said, some people find it very difficult to get vitamin A or vitamin D, and particularly for vitamin A, cod liver oil may be a very important source of that vitamin. Cod liver oil is a form of fish oil that happens to be high in the fat-soluble vitamins. Vitamin A is best found in liver. It’s better in my opinion to eat liver once a week, but there are a lot of people out there who are not going to eat liver once a week. So if you are using cod liver oil to get the vitamins that you can’t get from food—and I should point out that vitamin A can also be derived from plant foods, but many people genetically or for other reasons don’t derive it very well from plant foods.
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.
Animal studies show potent reduction of liver fat stores, glucose levels, and cholesterol levels in mice supplemented with krill oil while being fed a high fat diet.64,65 While many of these effects are seen with fish oil as well, studies show that krill oil, with its unique phospholipid structure, had the added benefit of increasing fat-burning in mitochondria while reducing new glucose production in the liver.66,67 As with so many other complex disease processes, utilizing multiple pathways to reduce disease is a highly effective strategy.67
An animal study involving the omega-3 ETA discovered that subjects experienced a drop in overall inflammation similar to that caused by NSAIDs (non-steroidal anti-inflammatory drugs), but without the dangerous gastrointestinal side effects. The study authors also pointed out that eicosapentaenoic acid seems to be even more potent than the conventional omega-3s found in fish oil supplements (EPA/DHA). (56)
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
The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.
Jump up ^ Martins, Julian G (2009). "EPA but Not DHA Appears to Be Responsible for the Efficacy of Omega-3 Long Chain Polyunsaturated Fatty Acid Supplementation in Depression: Evidence from a Meta-Analysis of Randomized Controlled Trials". Journal of the American College of Nutrition. 28 (5): 525–42. doi:10.1080/07315724.2009.10719785. PMID 20439549.
56. Davidson MH, Stein EA, Bays HE, et al. COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29:1354–1367. [PubMed]
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).
Meta‐analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all‐cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high‐quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high‐quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses – LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted.
Dr. Holub has provided the questions and answers for several emails he has received over the years regarding omega-3 fatty acids for health.  If you have a question regarding omega-3, it is likely that Dr. Holub has answered it either here in this section, or elsewhere on the site (e.g. check the scientific overview section for general questions regarding omega-3).  To quickly find your answer, please use our search bar located in the top right section of this page.  After searching our site, and  you still cannot find the answer to your question, we invite you to ask Dr. Holub a question here.
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The hypotriglyceridemic effect of fish oil is well established and is related to both dose and baseline triglyceride level. Patients with triglycerides <90 mg/dL will be negligibly affected unless very high doses of omega-3 FA are used.67,68 However, in patients with triglycerides >200 mg/dL, who are treated with 4 g/d of fish oil, a 30% reduction in triglycerides is expected.17,69 For patients with triglycerides >500 mg/dL who are at risk for pancreatitis, the National Cholesterol Education Program Adult Treatment Panel III guidelines recommend using fish oil supplements as an adjunctive therapy to fibrates and nicotinic acid.70 Lovaza capsules have been shown to be effective, safe, and comparable to gemfibrozil in treating triglycerides at this range.71,72 The official label recommendation for Lovaza is for patients with triglycerides >500 mg/dL.73
Omega-3s are important components of the membranes that surround each cell in your body. DHA levels are especially high in retina (eye), brain, and sperm cells. Omega-3s also provide calories to give your body energy and have many functions in your heart, blood vessels, lungs, immune system, and endocrine system (the network of hormone-producing glands).
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.
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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