For dry eye: Fish oil supplements providing EPA 360-1680 mg and DHA 240-560 mg have been used for 4-12 weeks. Some people used the specific product (PRN Dry Eye Omega Benefits softgels). A specific combination product containing EPA 450 mg, DHA 300 mg, and flaxseed oil 1000 mg (TheraTears Nutrition, Advanced Nutrition Research; Caruso’s Natural Health UltraMAX fish oil, Sydney, New South Wales, Australia) has been used once daily for 90 days.
First, EPA inhibits the enzyme that produces arachidonic acid. Second, EPA impedes the release of arachidonic acid from cell membranes (where it is stored) and its metabolization once it is released. Without this release and metabolization, your body can’t make eicosanoids. The result is lower risk of the inflammation that would have been caused by all that arachidonic acid going to eicosanoids.

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.
Due to the anticipated heterogeneity, a random-effects meta-analysis was chosen rather than a fixed-effects meta-analysis because random-effects modeling is more stringent and incorporates an among-study variance in the calculations. The entire meta-analysis procedure was performed on the platform of Comprehensive Meta-analysis statistical software, version 3 (Biostat). Under the preliminary assumption that the scales for anxiety symptoms are heterogeneous among the recruited studies, we chose Hedges g and 95% confidence intervals to combine the effect sizes, in accordance with the manual of the Comprehensive Meta-analysis statistical software, version 3. Regarding the interpretation of effect sizes, we defined Hedges g values 0 or higher as a better association of treatment with reduced anxiety symptoms of omega-3 PUFAs than in controls. For each analysis, a 2-tailed P value less than .05 was considered to indicate statistical significance. When more than 1 anxiety scale was used in a study, we chose the one with the most informative data (ie, mean and standard deviation [SD] before and after treatment). We entered the primary outcome provided in the included articles or obtained from the original authors. As for the variance imputation, we mainly chose the mean and SD before and after treatment. Later, we entered the mean and SD and calculated the effect sizes based on the software option, standardized by post score SD. In the case of studies with 2 active treatment arms, we merged the 2 active treatment arms into 1 group. If these 2 active treatment arms belonged to different subgroups (ie, different PUFA dosage subgroups), we kept them separate. Regarding the numbers of participants counted, we chose intention-to-treat as our priority. If there were insufficient data in the intention to treat group (ie, some studies only provided the changes in anxiety severity in those participants completing trials), we chose instead the per-protocol numbers of participants.

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.
In recent years, many people – particularly those who strictly follow a vegetarian or vegan diet – have believed that they do not have to consume animal products to get omega-3s, as long as they are consuming high amounts of plant-based omega-3s. But, as I mentioned before, most of the health benefits that you can get from omega-3 fats are linked to animal-based EPA and DHA fats – not plant-based ALA. They are simply NOT interchangeable.
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
After just seven days, those supplementing with krill had their CRP levels reduced by 19.3%, while in the placebo group, CRP levels rose by 15.7%. Even more impressive, the krill benefit was long-lasting. The krill group’s CRP levels continued to fall by 29.7% at 14 days, and 30.9% at 30 days. More importantly from the patients’ points of view, the krill oil supplement reduced pain scores by 28.9%, reduced stiffness by 20.3%, and reduced functional impairment by 22.8%.
“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."
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.
Some people who are hypersensitive to fish or have a known allergy to fish products may have a negative reaction to fatty acids which were derived from fish. Some fish oil tablets are also produced with alpha-linolenic acids which come from nuts, which may aggravate those which have an allergy to these products. In many cases these allergies will manifest themselves as a skin rash, but the symptoms could be more severe depending on the severity of your allergies. People with this concern will need to avoid using these products.
Makrides et al. (25)	Double-blind, placebo-controlled, randomized	2399 (n = 1197 supplemented, n = 1202 placebo; 726 children were followed up with)	DHA (fish-oil capsules providing 800 mg/d DHA)	Supplementation did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in offspring during early childhood

(How much omega-3 is necessary to increase one’s omega-3 index?  Studies show it can take between 1800 – 2000 mg of EPA/DHA daily to move a person’s index by 4 – 5 percentage points (12). Importantly, this is a much larger dose than you’d get swallowing one or two regular fish oil capsules and could well explain why many traditional omega-3 products fail to deliver results.)


The evidence linking the consumption of marine omega−3 fats to a lower risk of cancer is poor.[8][13] With the possible exception of breast cancer,[8][14][15] there is insufficient evidence that supplementation with omega−3 fatty acids has an effect on different cancers.[5][16] The effect of consumption on prostate cancer is not conclusive.[8][15] There is a decreased risk with higher blood levels of DPA, but an increased risk of more aggressive prostate cancer was shown with higher blood levels of combined EPA and DHA.[17] In people with advanced cancer and cachexia, omega−3 fatty acids supplements may be of benefit, improving appetite, weight, and quality of life.[18]
In general, most health organizations agree 250–500 milligrams of EPA and DHA combined each day is a reasonable amount to support healthy individuals. However, people with heart problems (or those with a high risk of heart disease), depression, anxiety and cancer (and possibly more conditions) may benefit from higher doses — up to 4,000 milligrams per day for some heart-related conditions. (5)
A scientific review in 2014 evaluated study findings on omega-3 intake in relation to the prevention and treatment of breast cancer, the most prevalent cancer among women. The review found that EPA and DHA, as well as ALA, can differentially inhibit breast tumor development. According to this review, there is solid evidence to support the use of omega-3s as “a nutritional intervention in the treatment of breast cancer to enhance conventional therapeutics, or potentially lowering effective doses.” (16) Additionally, a 2016 study found that “very high fish consumption in early adulthood to midlife may be associated with decreased risk of breast cancer.” (17)
In the United States, the Institute of Medicine publishes a system of Dietary Reference Intakes, which includes Recommended Dietary Allowances (RDAs) for individual nutrients, and Acceptable Macronutrient Distribution Ranges (AMDRs) for certain groups of nutrients, such as fats. When there is insufficient evidence to determine an RDA, the institute may publish an Adequate Intake (AI) instead, which has a similar meaning, but is less certain. The AI for α-linolenic acid is 1.6 grams/day for men and 1.1 grams/day for women, while the AMDR is 0.6% to 1.2% of total energy. Because the physiological potency of EPA and DHA is much greater than that of ALA, it is not possible to estimate one AMDR for all omega−3 fatty acids. Approximately 10 percent of the AMDR can be consumed as EPA and/or DHA.[105] The Institute of Medicine has not established a RDA or AI for EPA, DHA or the combination, so there is no Daily Value (DVs are derived from RDAs), no labeling of foods or supplements as providing a DV percentage of these fatty acids per serving, and no labeling a food or supplement as an excellent source, or "High in..."[citation needed] As for safety, there was insufficient evidence as of 2005 to set an upper tolerable limit for omega−3 fatty acids,[105] although the FDA has advised that adults can safely consume up to a total of 3 grams per day of combined DHA and EPA, with no more than 2 g from dietary supplements.[8]
Fish oils might slow blood clotting. Taking fish oils along with medications that also slow clotting might increase the chances of bruising and bleeding.Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.
Irving, G. F., Freund-Levi, Y., Eriksdotter-Jonhagen, M., Basun, H., Brismar, K., Hjorth, E., Palmblad, J., Vessby, B., Vedin, I., Wahlund, L. O., and Cederholm, T. Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer's disease: the omega-3 Alzheimer's disease study. J Am Geriatr Soc 2009;57(1):11-17. View abstract.
Pay attention to the quality of fish oil when purchasing it. It is obtained from almost all fishes – fresh water, farm, ocean, deep sea and shallow sea fish. All these fishes can be contaminated with toxic compounds such as mercury, arsenic, lead, forms of calcium, furans, dioxins, PCBs, and methylmercury, and can negatively affect the human body. Therefore, the fish oil used must be pure. Many companies sell ultra refined or distilled fish oil, but you should always check if the standards have been followed and research on the company or the product before adding it to your diet.
This article had several limitations and the findings need to be considered with caution. First, our participant population is too heterogeneous because of our broad inclusion criteria, which might be true if considering current Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases diagnostic systems. However, the novel Research Domain Criteria consider anxiety to be one of the major domains in Negative Valence Systems. Trials should be conducted in populations in which anxiety is the main symptom irrespective of the presence or absence of diagnosis of anxiety disorder. Second, because of the limited number of recruited studies and their modest sample sizes, the results should not be extrapolated without careful consideration. Third, the significant heterogeneity among the included studies (Cochran Q, 178.820; df, 18; I2, 89.934%; P < .001) with potential influence by some outlier studies, such as the studies by Sohrabi et al56 and Yehuda et al,61 would be another major concern. Therefore, clinicians should pay attention to this aspect when applying the results of the current meta-analysis to clinical practice, particularly when considering the subgroups of these 2 studies (ie, subgroups with specific clinical diagnoses, with <2000 mg/d, with EPA <60%, and with placebo-controlled trials).

Nine studies with 10 data sets used omega-3 PUFA dosages of less than 2000 mg/d.35,47,48,51,53,55,56,60,61 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, 9; Hedges g, 0.457; 95% CI, –0.077 to 0.991; P = .09) (Figure 3B). Ten studies with 10 data sets used omega-3 PUFA dosages of at least 2000 mg/d.33,34,36,49,50,52,54,55,57-59 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, 11; Hedges g, 0.213; 95% CI, 0.031-0.395; P = .02) (Figure 3B). Furthermore, there was no significantly different estimated effect sizes between these 2 subgroups by the interaction test (P = .40).


In short, there is no single optimal EPA:DHA ratio. If we are really healthy, with an optimal omega-6 to omega-3 ratio (from a diet rich in omega-3 fatty acids and low in grains and vegetable oils) and have an active, stress-free lifestyle, relying on standard fish oil in the natural 1.5:1 EPA:DHA ratio or simply consuming oily fish is completely adequate.
Here is a brief on omega-3 fatty acids: There are three types of omega-3 fatty acids, namely alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). All three are important for the body. Vegetable sources, including flaxseed oil, soybean oil, hemp oil, canola oil, walnut oil, rapeseed, perilla, chia, and tofu are rich in ALA. The human body has the ability to convert ALA to DHA and EPA, though there are certain limitations to this conversion.
ODS seeks to strengthen knowledge and understanding of dietary supplements by evaluating scientific information, supporting research, sharing research results, and educating the public. Its resources include publications (such as Dietary Supplements: What You Need to Know), fact sheets on a variety of specific supplement ingredients and products (such as vitamin D and multivitamin/mineral supplements), and the PubMed Dietary Supplement Subset
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.
The GISSI-Prevenzione trial40 showed similar findings. In this open-label trial, 11,324 post-MI patients were followed for 3.5 years after randomization to either 1 g/d of omega-3 FA, vitamin E, both, or none. In the 2836 patients assigned to only omega-3 FA, the primary end point of death, nonfatal MI or stroke, was reduced by 10%. This decreased risk occurred despite a minimal triglyceride-lowering effect because of the relatively low dose of omega-3 FA. Of note, the GISSI-Prevenzione trial was done prior to the pervasive use of lipid-lowering agents. Only about 40% of patients were on any form of lipid-lowering therapy.
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.
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.
Dioxins and PCBs may be carcinogenic at low levels of exposure over time. These substances are identified and measured in one of two categories, dioxin-like PCBs and total PCBs. While the U.S. FDA has not set a limit for PCBs in supplements, the Global Organization for EPA and DHA (GOED) has established a guideline allowing for no more than 3 picograms of dioxin-like PCBs per gram of fish oil. In 2012, samples from 35 fish oil supplements were tested for PCBs. Trace amounts of PCBs were found in all samples, and two samples exceeded the GOED‘s limit.[52] Although trace amounts of PCBs contribute to overall PCB exposure, Consumerlab.com claims the amounts reported by tests it ordered on fish oil supplements are far below those found in a single typical serving of fish.[52]

2. Omega-3 normalizes and regulates your cholesterol triglyceride levels. Compared to a statin, both fish oil and krill oil are more efficient in doing this. According to a study comparing the efficiency of krill and fish oils in reducing triglyceride levels,7 both oils notably reduced the enzyme activity that causes the liver to metabolize fat, but krill had a more pronounced effects, reducing liver triglycerides significantly more.

The University of East Anglia (UEA) is a UK Top 15 university. Known for its world-leading research and outstanding student experience, it was awarded Gold in the Teaching Excellence Framework and  is a leading member of Norwich Research Park, one of Europe’s biggest concentrations of researchers in the fields of environment, health and plant science. www.uea.ac.uk.
Dry eye. Higher intake of fish oil from the diet has been linked to a lower risk of dry eye in women. But the effects of fish oil in people with dry eye are inconsistent. Some research shows that fish oil reduces dry eye symptoms such as pain, blurred vision, and sensitivity. But fish oil doesn’t seem to improve other signs and symptoms of dry eye such as tear production and damage to the surface of the eye. Taking fish oil also doesn’t improve signs and symptoms of dry eye when used with other dry eye treatments.
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