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.

Because of the preliminary state of knowledge on the effects of omega-3 PUFA treatment on anxiety, we decided to include as many studies as possible and not to set further limitations on specific characteristics, such as length of study, diagnosis, omega-3 PUFA dosage, omega-3 PUFA preparation (EPA to DHA ratio), rated anxiety coding scale, or type of control. Therefore, we chose to make the inclusion criteria as broad as possible to avoid missing any potentially eligible studies. The inclusion criteria included clinical trials in humans (randomized or nonrandomized), studies investigating the effects of omega-3 PUFA treatment on anxiety symptoms, and formal published articles in peer-reviewed journals. The clinical trials could be placebo controlled or non–placebo controlled. The target participants could include healthy volunteers, patients with psychiatric illness, and patients with physical illnesses other than psychiatric illnesses. The exclusion criteria included case reports or series, animal studies or review articles, and studies not investigating the effects of omega-3 PUFA treatment on anxiety symptoms. We did not set any language limitation to increase the number of eligible articles. Figure 1 shows the literature search and screening protocol.

Most brands of fish oil have been proven safe, free of detectable traces of mercury, and do not contain unsafe levels of PCBs (polychlorinated biphenyls), a toxin and pollutant believed to pose various health threats. To avoid contaminants in an unrefined supplement, it's best to choose a fish-oil supplement made from small, oily fish like anchovy, sardines or menhaden.
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.

AAKG β-hydroxy β-methylbutyrate Carnitine Chondroitin sulfate Cod liver oil Copper gluconate Creatine/Creatine supplements Dietary fiber Echinacea Elemental calcium Ephedra Fish oil Folic acid Ginseng Glucosamine Glutamine Grape seed extract Guarana Iron supplements Japanese Honeysuckle Krill oil Lingzhi Linseed oil Lipoic acid Milk thistle Melatonin Red yeast rice Royal jelly Saw palmetto Spirulina St John's wort Taurine Wheatgrass Wolfberry Yohimbine Zinc gluconate


In addition, there was 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 adolescent subgroup (aged <18 years) (k, 3; Hedges g, 0.020; 95% CI, –0.209 to 0.250; P = .86),48,53,57 in the adult subgroup (aged ≥18 years but <60 years) (k, 11; Hedges g, 0.388; 95% CI, –0.012 to 0.788; P = .06),33,35,36,47,49-51,54-56,59 or in the elderly subgroup (aged ≥60 years) (k, 3; Hedges g, –0.112; 95% CI, –0.406 to 0.181; P = .45).52,58,60 These insignificant results might be due to the smaller sample sizes in each subgroup.
Children: Fish oil is POSSIBLY SAFE when taken by mouth appropriately. Fish oil has been used safely through feeding tubes in infants for up to 9 months. But young children should not eat more than two ounces of fish per week. Fish oil is POSSIBLY UNSAFE when consumed from dietary sources in large amounts. Fatty fish contain toxins such as mercury. Eating contaminated fish frequently can cause brain damage, mental retardation, blindness and seizures in children.
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.
The ultimate goal of using omega-3 fatty acids is the reduction of cellular inflammation. Since eicosanoids derived from arachidonic acid (AA), an omega-6 fatty acid, are the primary mediators of cellular inflammation, EPA becomes the most important of the omega-3 fatty acids to reduce cellular inflammation for a number of reasons. First, EPA is an inhibitor of the enzyme delta-5-desaturase (D5D) that produces AA (1). The more EPA you have in the diet, the less AA you produce. This essentially chokes off the supply of AA necessary for the production of pro-inflammatory eicosanoids (prostaglandins, thromboxanes, leukotrienes, etc.). DHA is not an inhibitor of this enzyme because it can’t fit into the active catalytic site of the enzyme due to its larger spatial size. As an additional insurance policy, EPA also competes with AA for the enzyme phospholipase A2 necessary to release AA from the membrane phospholipids (where it is stored). Inhibition of this enzyme is the mechanism of action used by corticosteroids. If you have adequate levels of EPA to compete with AA (i.e. a low AA/EPA ratio), you can realize many of the benefits of corticosteroids but without their side effects. That’s because if you don’t release AA from the cell membrane then you can’t make inflammatory eicosanoids. Because of its increased spatial dimensions, DHA is not a good competitor of phospholipase A2 relative to EPA. On the other hand, EPA and AA are very similar spatially so they are in constant competition for the phospholipase A2 enzyme just as both fatty acids are in constant competition for the delta-5 desaturase enzyme. This is why measuring the AA/EPA ratio is such a powerful predictor of the state of cellular inflammation in your body.
An excessive dosage of fish oil can have adverse allergies and side effects on the body. Furthermore, fish oil can be problematic if you have certain conditions so it is necessary to consume fish oil supplements cautiously. Moreover, it can be consumed in various forms. These include eating the fish directly by baking, roasting, frying, grilling, broiling, or smoking it. It can also be consumed in the form of concentrated dietary supplements like liquid, tablet, capsule, pill, or soft gels. Also, there are various pharmaceutical grades of the oil. It is not necessary to constantly consume pharmaceutical-grade oil or even supplements. You should also consult your doctor to confirm the mode of consuming fish oil and the overall need for it in your diet.

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 current American diet has changed over time to be high in SFA and low in omega-3 fatty acids (12). This change in eating habits is centered on fast food containing high amounts of saturated fat, which has small amounts of essential omega-3 PUFA compared with food prepared in the home (13). Seafood sources such as fish and fish-oil supplements are the primary contributors of the 2 biologically important dietary omega-3 fatty acids, EPA and DHA (14–16). This low intake of dietary EPA and DHA is thought to be associated with increased inflammatory processes as well as poor fetal development, general cardiovascular health, and risk of the development of Alzheimer's disease (AD).

Australian researchers published results of a study examining the effects of fish oil on weight loss in combination with diet and exercise in the May 2007 issue of American Journal of Clinical Nutrition. The results show that a combination of fish oil supplements and regular exercise can reduce body fat while also improving heart and metabolic health. The fish supplementation group had lowered triglycerides, increased HDL cholesterol and improved blood flow. Overall, adding fish oil to a current exercise program (and a overall healthy lifestyle) looks like it can decrease body fat as well as cardiovascular disease risk. (32)

Jump up ^ Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, Kris-Etherton PM, Lennie TA, Levi M, Mazzone T, Pennathur S (May 2011). "Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association". Circulation. 123 (20): 2292–333. doi:10.1161/CIR.0b013e3182160726. PMID 21502576.
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).
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.
A 2009 metastudy found that patients taking omega-3 supplements with a higher EPA:DHA ratio experienced fewer depressive symptoms. The studies provided evidence that EPA may be more efficacious than DHA in treating depression. However, this metastudy concluded that due to the identified limitations of the included studies, larger, randomized trials are needed to confirm these findings.[40]
Jump up ^ Heartney, Eleanor (2007). "Zhang Huan: Becoming the Body". Zhang Huan: Altered States. Charta and Asia Society. ISBN 978-8881586417. Retrieved 2014-10-23. This becomes abundantly clear in the work of Chinese body artist Zhang Huan. In the course of his career, Zhang Huan has subjected himself to painful trials: sitting motionless for hours in an outhouse covered in honey and fish oil while flies crawled over his body [...].
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.
Higher visual acuity after DHA supplementation is a consistent finding in infants born preterm. For infants born at term, the results are less consistent and are better explained by differences in sensitivity of the visual acuity test (electrophysiologic tests being more sensitive than subjective tests) or by differences in the amount of DHA included in the experimental formula.
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.
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Fish oil supplements vary in the amounts and ratios of DHA and EPA they contain. For example, salmon oil naturally contains more DHA than EPA; a supplement derived from algae may only contain DHA. Krill oil contains significant amounts of both EPA and DHA. Read the labels and remember whatever supplement you buy, it must have at least 600 mg of DHA.
A new Cochrane systematic review, published today in the Cochrane Library, combines the results of seventy-nine randomised trials involving 112,059 people. These studies assessed effects of consuming additional omega 3 fat, compared to usual or lower omega 3, on diseases of the heart and circulation. Twenty-five studies were assessed as highly trustworthy because they were well designed and conducted.

The differing actions of EPA and DHA, together with their competitive uptake, help to explain why studies that attempt to use standard fish oil therapeutically (where DHA and EPA are combined, in a natural ratio of approximately 1.5:1) are either less beneficial than expected, or even completely ineffective. Standard EPA/DHA fish oils are more suitable for everyday wellbeing, to compensate for a lack of fish in the diet and to meet a suggested intake.
In a 2009 joint study by the USDA and researchers at Clemson University in South Carolina, grass-fed beef was compared with grain-finished beef. The researchers found that grass-finished beef is higher in moisture content, 42.5% lower total lipid content, 54% lower in total fatty acids, 54% higher in beta-carotene, 288% higher in vitamin E (alpha-tocopherol), higher in the B-vitamins thiamin and riboflavin, higher in the minerals calcium, magnesium, and potassium, 193% higher in total omega−3s, 117% higher in CLA (cis-9, trans-11 octadecenoic acid, a cojugated linoleic acid, which is a potential cancer fighter), 90% higher in vaccenic acid (which can be transformed into CLA), lower in the saturated fats linked with heart disease, and has a healthier ratio of omega−6 to omega−3 fatty acids (1.65 vs 4.84). Protein and cholesterol content were equal.[86]
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.

The absence of DHA in many pure EPA trials, and therefore lack of competition between EPA and DHA during digestion and consequently for uptake, is considered to be partly responsible for the positive outcomes. Simply put, pure EPA delivers more EPA into cells where it is needed than combined EPA & DHA blends. Consequently, oils containing DHA may not be suitable for a variety of conditions when treatment relies on increasing levels of EPA and its end products.
To avoid fish oil supplements containing mercury or other harmful contaminants, purchase supplements from a reputable source that clearly tests for these health-hazardous contaminants in its products. These tests should be ideally conducted by a third-party, and a certificate of analysis should indicate the levels of purity from environmental toxins.
Davidson, M. H., Stein, E. A., Bays, H. E., Maki, K. C., Doyle, R. T., Shalwitz, R. A., Ballantyne, C. M., and Ginsberg, H. N. 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(7):1354-1367. View abstract.
For slowing weight loss in patients with cancer: 30 mL of a specific fish oil product (ACO Omega-3, Pharmacia, Stockholm, Sweden) providing 4.9 grams of EPA and 3.2 grams of DHA daily for 4 weeks has been used. 7.5 grams of fish oil daily providing EPA 4.7 grams and DHA 2.8 grams has been used for about 6 weeks. In addition, two cans of a fish oil nutritional supplement containing 1.09 grams of EPA and 0.96 grams of DHA per can have been used daily for up to 7 weeks.
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