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.
Bergmann, R. L., Haschke-Becher, E., Klassen-Wigger, P., Bergmann, K. E., Richter, R., Dudenhausen, J. W., Grathwohl, D., and Haschke, F. Supplementation with 200 mg/day docosahexaenoic acid from mid-pregnancy through lactation improves the docosahexaenoic acid status of mothers with a habitually low fish intake and of their infants. Ann Nutr Metab 2008;52(2):157-166. View abstract.

First, always remember that it’s the omega-3s that count. When making your purchase, be sure to determine the amount of omega-3s per serving. Many doctors often recommend 1000 to 1200 mg of fish oil because that amount of fish oil contains the total amount of omega-3s the doctor wants you to consume. 1000 mg or 1200 mg of fish oil doesn’t equal 1000 or 1200 mg of omega-3s. A standard 1000 mg fish oil softgel provides around 300 mg of omega-3s (and even less of the important EPA and DHA), and to meet the 500 mg EPA and DHA recommendation, a minimum of two softgels would be necessary. Make sure to read the “Supplement Facts” label to determine the amount of EPA and DHA in a fish oil/omega-3 supplement.


Omega 3 fatty acids—found in supplements and naturally in some foods like certain fish, and nuts and seeds—have long been touted for their health benefits, especially heart health. Yet, a lot is still unknown, including whether it's better to get your omega 3 fats from pills or in food—and the debate continues regarding how much they may actually help you avoid heart disease.
Fish and omega-3 fatty acids. If you keep up with the latest nutrition news, you may have a pretty good sense of what they offer. But, if you're like many people, you still can't tell your omega-3s from your omega-6s -- and you sure as heck can't pronounce eicosapentaenoic acid. That's OK. Our fishing expedition turned up some interesting facts to share about omega-3 fatty acids and fish.
Flaxseed (or linseed) (Linum usitatissimum) and its oil are perhaps the most widely available botanical source of the omega−3 fatty acid ALA. Flaxseed oil consists of approximately 55% ALA, which makes it six times richer than most fish oils in omega−3 fatty acids.[126] A portion of this is converted by the body to EPA and DHA, though the actual converted percentage may differ between men and women.[127]
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.
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.
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.
Your retina contains quite a bit of DHA, making it necessary for that fatty acid to function. (90) The National Eye Institute, part of the National Institutes of Health, concludes that there is “consistent evidence” suggesting long-chain polyunsaturated fatty acids DHA and EPA are necessary for retinal health and may help protect the eyes from disease. (91)
There’s evidence that points to the mechanism behind the effects of fish oil on body composition, showing that fat burning at rest is increased with 6 grams/day of fish oil supplementation, and additional research suggests that higher omega-3 levels may be helpful for enhancing satiety during weight loss efforts. Other evidence suggests that fat loss may be a side-effect of the reduction in inflammation that fish oil can help with. Any way you look at it, supporting your dietary habits with 4 or more grams of fish oil per day is probably a good idea!

Thanks to fatdog11 for that informative post about PCB’s in fish-oil supplements. Are these same toxicity levels found in fish themselves, or possibly are these levels so high only in highly concentrated fish-oil products? Also, can fatdog11 please inform us more about algae-derived omega-3. What are the DHA and EPA levels in these capsules? What is the cost, and where can they be purchased?


The European Journal of Neuroscience published a study in 2013 showing that fish oil reversed all anxiety-like and depression-like behavior changes induced in rats. This is an interesting study because it stresses the importance of supplementing with fish oil at “critical periods of brain development.” (10) This is exactly why I recommend giving fish oil to our kids from early on to help them so they won’t develop anxiety or depression later in life.
Jump up ^ Chua, Michael E.; Sio, Maria Christina D.; Sorongon, Mishell C.; Morales Jr, Marcelino L. Jr. (May–June 2013). "The relevance of serum levels of long chain omega-3 polyunsaturated fatty acids and prostate cancer risk: a meta-analysis". Canadian Urological Association Journal. 7 (5–6): E333–43. doi:10.5489/cuaj.1056. PMC 3668400. PMID 23766835.
Heart rate variability, a possible surrogate outcome for the risk of sudden death, was assessed in a randomized trial of myocardial infarction (MI) survivors with an ejection fraction of 40%. In the 49 patients that were randomized to either fish oil or olive oil, Holter monitor recordings showed an increase in heart rate variability in the fish oil group.31 In a larger cohort assessed in the Japan EPA Lipid Intervention Study (JELIS),32 however, no difference in heart rate variability could be attributed to fish oil.

Lok CE, Moist L, Hemmelgarn BR, Tonelli M, Vazquez MA, Dorval M, Oliver M, Donnelly S, Allon M, Stanley K; Fish Oil Inhibition of Stenosis in Hemodialysis Grafts (FISH) Study Group. Effect of fish oil supplementation on graft patency and cardiovascular events among patients with new synthetic arteriovenous hemodialysis grafts: a randomized controlled trial. JAMA 2012;307(17):1809-16. View abstract.
Several studies suggest that people suffering symptoms of depression and/or anxiety see improvement after adding an omega-3 supplement to their routine, even in double-blinded, randomized, controlled trials. (29, 30, 31, 32, 33) At least one study comparing a common depression medication found omega-3 supplements to be just as effective in combating depression symptoms. (34)

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.


Jump up ^ Chua, Michael E.; Sio, Maria Christina D.; Sorongon, Mishell C.; Morales Jr, Marcelino L. Jr. (May–June 2013). "The relevance of serum levels of long chain omega-3 polyunsaturated fatty acids and prostate cancer risk: a meta-analysis". Canadian Urological Association Journal. 7 (5–6): E333–43. doi:10.5489/cuaj.1056. PMC 3668400. PMID 23766835.
Chemical structure of alpha-linolenic acid (ALA), an essential omega−3 fatty acid, (18:3Δ9c,12c,15c, which means a chain of 18 carbons with 3 double bonds on carbons numbered 9, 12, and 15). Although chemists count from the carbonyl carbon (blue numbering), biologists count from the n (ω) carbon (red numbering). Note that, from the n end (diagram right), the first double bond appears as the third carbon-carbon bond (line segment), hence the name "n-3". This is explained by the fact that the n end is almost never changed during physiological transformations in the human body, as it is more energy-stable, and other compounds can be synthesized from the other carbonyl end, for example in glycerides, or from double bonds in the middle of the chain.
The omega-3 index may also be helpful for assessing health risks beyond cardiovascular disease. Studies are currently investigating the relationship between omega-3 index levels and mental health issues, like depression (15, 16, 17), cognitive functioning (18, 19), body weight (20), as well as eye health issues, like macular degeneration (21), to name just a few.
Fish oil has only a small benefit on the risk of premature birth.[43][44] A 2015 meta-analysis of the effect of omega−3 supplementation during pregnancy did not demonstrate a decrease in the rate of preterm birth or improve outcomes in women with singleton pregnancies with no prior preterm births.[45] A systematic review and meta-analysis published the same year reached the opposite conclusion, specifically, that omega−3 fatty acids were effective in "preventing early and any preterm delivery".[46]
Although there was significant heterogeneity among the included studies (Cochran Q, 178.820; df, 18; I2, 89.934%; P < .001), the sensitivity test suggested that the main significant results of the meta-analysis would not change after removal of any of the included studies. However, through direct inspection of the forest plot, we detected the potential influence of some outliers, such as the studies by Sohrabi et al56 and Yehuda et al.61 These 2 studies evaluated anxiety symptoms with a visual analog scale of anxiety and test anxiety severity, which are seldom used in psychiatric research and lack a definite report to prove their equivalent sensitivity and specificity to some other frequently used anxiety rating scales, such as depression, anxiety, and stress scales or the Hamilton anxiety rating scale. Therefore, these studies might have affected the interpretation of the current meta-analysis.

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]
(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.)

Further, according to subgroup results based on the presence of specific clinical diagnoses or not, the association of omega-3 PUFA treatment with reduced anxiety symptoms was significantly higher in subgroups with specific clinical diagnoses than in subgroups without clinical conditions. Among 6 studies included in a meta-analysis of the effect of omega-3 PUFAs on depressive symptoms, the analysis showed a nearly null effect of omega-3 PUFAs on depressive symptoms in healthy participants.73 Although the reason for the null effect of omega-3 PUFAs on anxiety and depressive symptoms remains unclear, certain pathophysiological conditions might be required for omega-3 PUFAs to exert an association of treatment with reduced anxiety symptoms.


The GISSI-Heart Failure trial was the first blinded, randomized trial to assess the efficacy of fish oil supplements in patients with heart failure.51 The trial enrolled 7046 subjects with heart failure; 60% with New York Heart Association class II symptoms and 40% with a history of MI. The majority of patients were on a standard heart failure regimen, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, and spironolactone, but only 22% were on a statin. At an average of 3.9 years, the coprimary end points of death and death or hospital admission for cardiovascular reasons were reduced by approximately 9% with fish oil supplementation. Sudden cardiac death, a secondary end-point, showed a statistically nonsignificant relative risk reduction of 7% with fish oil. There was also a reduction in 2 other arrhythmia-related secondary end-points: first hospitalization for ventricular arrhythmia and presumed arrhythmic death.
Nielsen, A. A., Jorgensen, L. G., Nielsen, J. N., Eivindson, M., Gronbaek, H., Vind, I., Hougaard, D. M., Skogstrand, K., Jensen, S., Munkholm, P., Brandslund, I., and Hey, H. Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acids. Aliment.Pharmacol.Ther. 2005;22(11-12):1121-1128. View abstract.
Fish oil has been shown to have a direct electrophysiological effect on the myocardium. Initial experience with animal ischemia models demonstrated that the ventricular fibrillation threshold was increased in both animals fed or infused with omega-3 FA.23,24 This progressed to a demonstration, on a cellular and ion channel level, that omega-3 FA reduce both sodium currents and L-type calcium currents.25–29 It is hypothesized that during ischemia, a reduction in the sodium ion current protects hyperexcitable tissue, and a reduction in the calcium ion current reduces arrhythmogenic depolarizing currents.30
Fish oil is a concentrated source of omega-3 fats, which are also called ω-3 fatty acids or n-3 fatty acids. To get more scientific, omega-3s are long-chain polyunsaturated fatty acids, or PUFAs. Our bodies are able to make most of the fats we need need, but that’s not true for omega-3 fatty acids. When it comes to these essential fats, we need to get them from omega-3 foods or supplements.
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 [...].

In fact, fish oil is even dipping its way into mainstream medicine. In September 2018, Amarin Corporation, the biopharmaceutical developer of pharmaceutical-grade fish oil Vascepa, released preliminary findings of its double-blind clinical trial. In the study, researchers tracked more than 8,000 adults for a median 4.9 years. The mix of study participants had either established cardiovascular disease or type 2 diabetes and another cardiovascular disease risk factor, along with persistently elevated triglycerides.
Corresponding Author: Yutaka J. Matsuoka, MD, PhD, Division of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan (yumatsuo@ncc.go.jp); Kuan-Pin Su, MD, PhD, China Medical University Hospital, No. 2, Yude Road, North District, Taichung City, Taiwan 404 (cobolsu@gmail.com).
Muñoz MA, Liu W, Delaney JA, Brown E, Mugavero MJ, Mathews WC, Napravnik S, Willig JH, Eron JJ, Hunt PW, Kahn JO, Saag MS, Kitahata MM, Crane HM. Comparative effectiveness of fish oil versus fenofibrate, gemfibrozil, and atorvastatin on lowering triglyceride levels among HIV-infected patients in routine clinical care. J Acquir Immune Defic Syndr 2013;64(3):254-60. View abstract.
Fish oil has only a small benefit on the risk of premature birth.[43][44] A 2015 meta-analysis of the effect of omega−3 supplementation during pregnancy did not demonstrate a decrease in the rate of preterm birth or improve outcomes in women with singleton pregnancies with no prior preterm births.[45] A systematic review and meta-analysis published the same year reached the opposite conclusion, specifically, that omega−3 fatty acids were effective in "preventing early and any preterm delivery".[46]

Marchioli, R., Barzi, F., Bomba, E., Chieffo, C., Di, Gregorio D., Di, Mascio R., Franzosi, M. G., Geraci, E., Levantesi, G., Maggioni, A. P., Mantini, L., Marfisi, R. M., Mastrogiuseppe, G., Mininni, N., Nicolosi, G. L., Santini, M., Schweiger, C., Tavazzi, L., Tognoni, G., Tucci, C., and Valagussa, F. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 4-23-2002;105(16):1897-1903. View abstract.
Bo and I worked with Dr. Harris many years ago to measure the impact of eating one Omega Cookie® daily on the study participants’ omega-3 index levels, and we recently ran into him at ISFFAL. At the conference, we remeasured our omega-3 index and omega-6/omega-3 ratios, and a few weeks later, we got our results in the mail. For the two of us, it was exciting to get another concrete measure of how our daily omega-3 consumption impacted our scores. For the record, we take one vial of Omega Restore™ per night and frequently sneak an Omega Heaven® or Omega Cookie during the day.
After the age of five, the development of the brain and CNS starts to reduce and the body’s need for DHA reduces. This is a good time to increase EPA in the diet, as studies show that EPA can help with childhood behaviour and academic performance, as well as focus, attention and reducing aggression. Dry skin conditions, asthma and allergies are also common in children and good levels of EPA at this time can help reduce the inflammation associated with these issues.

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.
Jump up ^ Chua, Michael E.; Sio, Maria Christina D.; Sorongon, Mishell C.; Morales Jr, Marcelino L. Jr. (May–June 2013). "The relevance of serum levels of long chain omega-3 polyunsaturated fatty acids and prostate cancer risk: a meta-analysis". Canadian Urological Association Journal. 7 (5–6): E333–43. doi:10.5489/cuaj.1056. PMC 3668400. PMID 23766835.
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• Fish oil – Fish oil is among the primary ways that people enhance their intake of omega-3 fats. High-quality fish oils can certainly provide many health benefits. However, this oil is weak in antioxidants. This means that as you increase your omega-3 intake through fish oil consumption, you actually increase your need for added antioxidant protection.
Fish oil is also extremely beneficial for pregnant women and their children. Throughout pregnancy and also while breastfeeding, a woman’s omega-3 needs are even higher than usual. According to the American Pregnancy Association, most U.S. women are deficient in EPA and especially DHA going into pregnancy and get even more depleted during pregnancy, as the placenta supplies the fetus with DHA from the mother’s tissue. Omega-3 DHA is a critical building block of the fetal brain, eyes and nervous system. Once the baby is born, omega-3s continue to be vital to healthy brain development and immune function. (30)
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.
Belalcazar, L. M., Reboussin, D. M., Haffner, S. M., Reeves, R. S., Schwenke, D. C., Hoogeveen, R. C., Pi-Sunyer, F. X., and Ballantyne, C. M. Marine omega-3 fatty acid intake: associations with cardiometabolic risk and response to weight loss intervention in the Look AHEAD (Action for Health in Diabetes) study. Diabetes Care 2010;33(1):197-199. View abstract.
What are the benefits of cod liver oil? This article provides detailed information on the health benefits associated with cod liver oil, and its potential therapeutic properties. This article looks at some of the claims that cod liver oil might improve cardiovascular health, ease joint stiffness caused by arthritis, and repair wounds. Read on to learn more. Read now
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).
It helps maintain a good luster of the hair because omega-3 has growth stimulating properties since it provides nourishment to the follicles. It aids in the development of hair and in preventing hair loss. A good supply of protein is also necessary for hair growth, and since most fish varieties are rich in protein, eating fish helps to keep hair healthy.
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.
A 2012 study involved children from 6 to 12 years of age with ADHD who were being treated with methylphenidate and standard behavior therapy for more than six months. The parents of these children reported no improvement in behavior and academic learning using these standard treatments. The researchers randomly gave some of the children an omega-3 and omega-6 acid supplementation or a placebo. They found “statistically significant improvement” for the omega group in the following categories: restlessness, aggressiveness, completing work and academic performance. (5)
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.
“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."
The number, location, and orientation of the double bonds determine the health effects of fatty acids on the body. One aspect of this is their effect on triglycerides and LDL and HDL types of cholesterol, which in turn affect how much cholesterol gets deposited on the inside of blood vessels. There are also subtypes of LDL and HDL which are also likely important to their health effects.
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.
Omega-3 fatty acids have been shown to increase platelet responsiveness to subtherapeutic anticoagulation therapies, including aspirin. Recently, it was noted that patient response to aspirin for anticoagulation therapy is widely variable (45), and, thus, the number of patients with a low response to aspirin or aspirin resistance is estimated to range from <1% to 45%, depending on many variables. However, in patients with stable coronary artery disease taking low-dose aspirin, EPA+DHA supplementation has been proven to be as effective as aspirin dose escalation to 325 mg/d for anticoagulation benefits (45). The antiplatelet drug clopidogrel has also been associated with hyporesponsiveness in some patients. This could be attributed to poor patient compliance, differences in genes and platelet reactivity, variability of drug metabolism, and drug interactions. More importantly, in 1 study, patients receiving standard dual antiplatelet therapy (aspirin 75 mg/d and clopidogrel 600-mg loading dose followed by 75 mg/d) were assigned to either EPA+DHA supplementation or placebo. After 1 mo of treatment, the P2Y12 receptor reactivity index (an indicator of clopidogrel resistance) was significantly lower, by 22%, for patients taking EPA+DHA compared with patients taking placebo (P = 0.020) (46).
In your final paragraph, you suggest that a ratio of 2:1 EPA/DHA maybe best for reducing inflammation. Are you suggesting using two separate products to obtain that ratio? I can't see how it is achieveable through standard omega-3 products. Good fish oil brands are typically 60% or higher EPA, but never reach a 2:1 ratio in my product searches. According to case studies (link below), 1 gram of EPA per day (60% or more of the total omega-3 content) is sufficient and the highest efficacy.
Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.
Alpha-linolenic Acid (ALA): This plant-based omega-3 is found in green, leafy vegetables, flaxseeds, chia seeds and canola, walnut and soybean oils (although those rancid oils are not ones I generally recommend). ALA is known as a short-chain omega-3, meaning your body has to convert it into longer-chained EPA and DHA to synthesize it. This process is rather inefficient and only about one percent of the ALA you consume is converted to the long-chain version your body needs (although this percentage is slightly higher for women).
Doses for depression range from less than 1 g/day to 10 g/day, but most studies use doses between 1 and 2 g/day. In my practice, I recommend 1 to 2 g/day of an EPA+DHA combination, with at least 60% EPA, for major depression. I am more cautious in patients with bipolar depression, because the omega-3s may bring on mania, as can most antidepressants. In these individuals, I recommend using omega-3 cautiously, and preferably in combination with a prescription mood stabilizer.

Some high-quality omega-3 supplements will have lower amounts than EPA/DHA but accompany them with digestive enzymes. While it looks counterintuitive on a nutrition label, this is often done because there is debate about how much of the omega-3’s you actually absorb from supplements when taken alone. By coupling omega-3’s with a digestive enzyme blend, you are likely able to absorb more of the nutrient without having to consume as many grams.
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.

Bemelmans, W. J., Broer, J., Feskens, E. J., Smit, A. J., Muskiet, F. A., Lefrandt, J. D., Bom, V. J., May, J. F., and Meyboom-de Jong, B. Effect of an increased intake of alpha-linolenic acid and group nutritional education on cardiovascular risk factors: the Mediterranean Alpha-linolenic Enriched Groningen Dietary Intervention (MARGARIN) study. Am J Clin Nutr 2002;75(2):221-227. View abstract.
AD is a devastating disease for which there are limited treatment options and no cure. Memory loss is an early indicator of the disease, which is progressive, and leads to the inability of the patient to care for him- or herself and eventually to death (47). Currently, the number of individuals with AD is estimated to be 26.6 million and is expected to increase to 106.2 million by 2050 (48). There have been many studies conducted regarding the use of omega-3 fatty acid supplementation and AD (Table 2). DHA is present in large amounts in neuron membrane phospholipids, where it is involved in proper function of the nervous system, which is why it is thought to play a role in AD (49). A case-control study consisting of 148 patients with cognitive impairment [Mini-Mental State Examination (MMSE) score <24] and 45 control patients (MMSE score ≥24) showed that serum cholesteryl ester-EPA and -DHA levels were significantly lower (P < 0.05 and P < 0.001, respectively) in all MMSE score quartiles of patients with AD compared with control values (49). Another study found that a diet characterized by higher intakes of foods high in omega-3 fatty acids (salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, dark and green leafy vegetables), and a lower intake of foods low in omega-3 fatty acids (high-fat dairy products, red meat, organ meat, butter) was strongly associated with a lower AD risk (50). Image analysis of brain sections of an aged AD mouse model showed that overall plaque burden was significantly reduced by 40.3% in mice with a diet enriched with DHA (P < 0.05) compared with placebo. The largest reductions (40–50%) were seen in brain regions that are thought to be involved with AD, the hippocampus and parietal cortex (51). A central event in AD is thought to be the activation of multiple inflammatory cells in the brain. Release of IL-1B, IL-6, and TNF α from microglia cells may lead to dysfunction of the neurons in the brain (52). In 1 study, AD patients treated with EPA+DHA supplementation increased their plasma concentrations of EPA and DHA, which were associated with reduced release of inflammatory factors IL-1B, IL-6, and granulocyte colony–stimulating factor from peripheral blood mononuclear cells (53).

EPA, which is eicosapentaenoic acid, and DHA, which is docosahexaenoic acid, are two types of omega-3 fatty acids that are most commonly found in seafood. These polyunsaturated fats are known to have preventative health benefits and have been studied for their role in treating certain chronic conditions. In addition to dietary sources, certain supplements such as fish oil, are also rich in EPA and DHA.
There have been numerous clinical trials looking mainly at death, stroke, and cardiac outcomes related to omega 3 consumption, either in food or in supplements. Now the Cochrane Library has published the largest systematic review of these studies to date. Unfortunately, the review shows little benefit from consuming omega 3 fatty acid. This is a fairly extensive review with good statistical power:
Jatoi, A., Rowland, K., Loprinzi, C. L., Sloan, J. A., Dakhil, S. R., MacDonald, N., Gagnon, B., Novotny, P. J., Mailliard, J. A., Bushey, T. I., Nair, S., and Christensen, B. An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer-associated wasting: a North Central Cancer Treatment Group and National Cancer Institute of Canada collaborative effort. J.Clin.Oncol. 6-15-2004;22(12):2469-2476. View abstract.
Maternal nutrition guidelines have always stressed a diet including sufficient caloric and protein requirements, but recently fatty acids have also been deemed important (17). This is partially due to the fact that EPA and DHA supplementation during pregnancy has been associated with multiple benefits for the infant (Table 1). During pregnancy, the placenta transfers nutrients, including DHA, from the mother to the fetus (18). The amount of omega-3 fatty acid in the fetus is correlated with the amount ingested by the mother, so it is essential that the mother has adequate nutrition (19). The 2010 U.S. Department of Health and Human Services dietary guidelines recommend that women who are pregnant or breastfeeding should “consume 8 to 12 ounces of seafood per week from a variety of seafood types” (12). Ingesting 8–12 oz of seafood per week, depending on the type of fish, is equivalent to ∼300–900 mg EPA+DHA per day. Unfortunately, this amount is not being met by most mothers in the United States and Canada, which means that infants many not be receiving adequate amounts of these vital nutrients in the womb (20).
Before getting to know some of the fish oil side effects, you have to know more about fish oil, like its benefits and usages. Fish oil has become a popular supplement for athletes, as well as those looking to improve their overall health. Many claims have been made regarding the improvements to the body which can be made by using fish oil to increase the body's level of fatty omega-3 acids. Some of these claims have been backed up by studies, while others have not been proven with significant scientific evidence. There are also some precautions that need to be addressed if you will be taking fish oil regularly. People with certain health conditions may see a worsening of their symptoms if they increase their intake of fatty acids too quickly or with the wrong products.
Fish oil has been shown to have a direct electrophysiological effect on the myocardium. Initial experience with animal ischemia models demonstrated that the ventricular fibrillation threshold was increased in both animals fed or infused with omega-3 FA.23,24 This progressed to a demonstration, on a cellular and ion channel level, that omega-3 FA reduce both sodium currents and L-type calcium currents.25–29 It is hypothesized that during ischemia, a reduction in the sodium ion current protects hyperexcitable tissue, and a reduction in the calcium ion current reduces arrhythmogenic depolarizing currents.30
The GISSI-Heart Failure trial was the first blinded, randomized trial to assess the efficacy of fish oil supplements in patients with heart failure.51 The trial enrolled 7046 subjects with heart failure; 60% with New York Heart Association class II symptoms and 40% with a history of MI. The majority of patients were on a standard heart failure regimen, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, and spironolactone, but only 22% were on a statin. At an average of 3.9 years, the coprimary end points of death and death or hospital admission for cardiovascular reasons were reduced by approximately 9% with fish oil supplementation. Sudden cardiac death, a secondary end-point, showed a statistically nonsignificant relative risk reduction of 7% with fish oil. There was also a reduction in 2 other arrhythmia-related secondary end-points: first hospitalization for ventricular arrhythmia and presumed arrhythmic death.
This fact sheet by the Office of Dietary Supplements (ODS) provides information that should not take the place of medical advice. We encourage you to talk to your healthcare providers (doctor, registered dietitian, pharmacist, etc.) about your interest in, questions about, or use of dietary supplements and what may be best for your overall health. Any mention in this publication of a specific product or service, or recommendation from an organization or professional society, does not represent an endorsement by ODS of that product, service, or expert advice.
46. Gajos G, Rostoff P, Undas A, Piwowarska W. Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after pci to modify responsiveness to dual antiplatelet therapy) study. J Am Coll Cardiol. 2010;55:1671–8. [PubMed]
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.
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