Of great clinical importance, EPA and DHA supplementation during pregnancy has been associated with longer gestation and increased concentrations of EPA and DHA in fetal tissues (21). In 2005, preterm births accounted for 12.7% of all births in the United States, increasing the likelihood of health complications (22). Carrying a baby to term is very important because prematurity is the cause of various infant diseases and can lead to death; preterm delivery is an underlying factor for 85% of the deaths of normally formed infants (23). One mechanism by which EPA and DHA may decrease the incidence of preterm birth is by decreasing prostaglandin E2 and prostaglandin F2α production, therefore reducing inflammation within the uterus, which could be associated with preterm labor (21, 24). Several studies investigated EPA and DHA intake during pregnancy and its correlation with longer gestation. Conclusions were that EPA+DHA supplementation during pregnancy delayed the onset of delivery to term or closer to term; however, supplementation did not delay delivery to the point of being post-term (20, 23, 25). This supports the evidence that EPA+DHA ingestion leads to optimal pregnancy length. EPA+DHA supplementation reduced the HR of preterm delivery by 44% (95% CI: 14–64%) in those who consumed relatively low amounts of fish and 39% (95% CI: 16–56%) in those who consumed medium amounts of fish; however, a level of statistical significance was not met (P = 0.10) (23). The Judge et al. (20) study found that women who had DHA supplementation from gestation week 24 until full-term delivery carried their infants significantly (P = 0.019) longer than did the women in the placebo group. One study found that DHA supplementation after gestation week 21 led to fewer preterm births (<34 wk of gestation) in the DHA group compared with the control group (1.09% vs. 2.25%; adjusted RR, 0.49; 95% CI: 0.25–0.94; P = 0.03). Also, mean birth weight was 68 g heavier (95% CI: 23–114 g; P = 0.003) and fewer infants were of low birth weight in the DHA group compared with the control group (3.41% vs. 5.27%; adjusted RR, 0.65; 95% CI: 0.44–0.96; P = 0.03) (25).
Wohl, D. A., Tien, H. C., Busby, M., Cunningham, C., Macintosh, B., Napravnik, S., Danan, E., Donovan, K., Hossenipour, M., and Simpson, R. J., Jr. Randomized study of the safety and efficacy of fish oil (omega-3 fatty acid) supplementation with dietary and exercise counseling for the treatment of antiretroviral therapy-associated hypertriglyceridemia. Clin.Infect.Dis. 11-15-2005;41(10):1498-1504. View abstract.
Omega-3s have been studied in various mood disorders, such as postpartum depression, with some promising results. In bipolar disorder (manic depression), the omega-3s may be most effective for the depressed phase rather than the manic phase of the illness. The omega-3s have also been proposed to alleviate or prevent other psychiatric conditions including schizophrenia, borderline personality disorder, obsessive compulsive disorder, and attention deficit disorder. However, there is still not enough evidence to recommend the omega-3s in these conditions.
Yamagishi, K., Iso, H., Date, C., Fukui, M., Wakai, K., Kikuchi, S., Inaba, Y., Tanabe, N., and Tamakoshi, A. Fish, omega-3 polyunsaturated fatty acids, and mortality from cardiovascular diseases in a nationwide community-based cohort of Japanese men and women the JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study. J.Am.Coll.Cardiol. 9-16-2008;52(12):988-996. View abstract.
Fish oil therapy is efficacious and safe for patients with severe to moderate hypertriglyceridemia. Combination therapy with HMG-CoA reductase inhibitors is also efficacious and has not been associated with any serious adverse reactions. Fish oil therapy added to fenofibrate in patients with severe hypertriglyceridemia is also effective and safe. Accordingly, it may be a safe and effective adjunct in the pharmacotherapy of the mixed lipid disorder that is frequently encountered in patients with the metabolic syndrome and/or type II diabetes mellitus.
For several years now, the fish oil and Alzheimer’s disease connection has been studied with consistent results. The essential fatty acids vital for brain function that are found in fish oil can not only slow cognitive decline, but can help prevent brain atrophy in older adults. A study published in the FASEB Journal looked at the health effects of four- to 17-month dietary supplementation with omega-3 fatty acids and antioxidants. The findings once again confirm the potential for fish oil to be used as a weapon to fend off the onset of cognitive decline and Alzheimer’s disease. (8)
FDA pregnancy category C. It is not known whether Fish Oil will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using Fish Oil. It is not known whether omega-3 polyunsaturated fatty acids pass into breast milk or if this could harm a nursing baby. Do not use Fish Oil without telling your doctor if you are breast-feeding a baby. Do not give this medication to anyone under 18 years old.
It’s uncertain whether omega-3 fatty acid supplements are helpful for depression. Although some studies have had promising results, a 2015 evaluation of 26 studies that included more than 1,400 people concluded that if there is an effect, it may be too small to be meaningful. Other analyses have suggested that if omega-3s do have an effect, EPA may be more beneficial than DHA and that omega-3s may best be used in addition to antidepressant medication rather than in place of it. 
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.

Hooper, L., Thompson, R. L., Harrison, R. A., Summerbell, C. D., Ness, A. R., Moore, H. J., Worthington, H. V., Durrington, P. N., Higgins, J. P., Capps, N. E., Riemersma, R. A., Ebrahim, S. B., and Davey, Smith G. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ 4-1-2006;332(7544):752-760. View abstract.
What's more, ALA is just a precursor to EPA and DHA. You need certain enzymes to elongate and desaturate ALA so it can become long-chained omega-3s. Unfortunately, this does not work in some people, particularly those who are deficient in certain vitamins and minerals, leading to very low conversion rates – only 1 percent of ALA is converted to EPA/DHA. In some, the conversion can even dip as low as 0.1 to 0.5 percent!
Although there are no randomized data on fish oil consumption and protection from sudden death, observational studies have linked omega-3 FA with the prevention of sudden death. In a population-based, case-control study of sudden cardiac death victims, the mean red blood cell membrane omega-3 FA level of the lowest quartile, when compared with the mean level of the third quartile, was associated with a relative risk reduction of 70%.33 A similar finding was appreciated in a nested, prospective, case-control study of the Physician Health Study cohort of 22,000 healthy males. In the 119 patients that succumbed to sudden death, baseline omega-3 FA blood levels were significantly lower than in matched controls.34 Finally, in an analysis of data from the Nurses Health Study, a cohort study of 84,688 women, an inverse association was shown between fish consumption and CAD-related death. The investigators concluded that the reduction in CAD deaths was likely due to a reduction in sudden deaths, as there was no difference in the rate of MI when comparing high and low fish consumption.35

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.
Research conducted by Professor Peter Howe at the University of South Australia has shown that fish oil improves the efficacy of exercise in attempts to reduce weight. Volunteers who were given fish oil in their diet showed greater weight loss as compared to those who did not regularly consume it. Fish oil contains omega-3 fatty acids, which help to promote the weight loss, so a combination of physical workout and intake of this oil helps in reducing body fat significantly faster.
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.

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


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).
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.
According to the National Psoriasis Foundation, fish oil can aid in preventing or slowing heart disease, which is especially great for psoriasis and psoriatic arthritis sufferers who are at a higher risk of developing heart disease. (27) When it comes to using fish oil supplements for the alleviation of psoriasis symptoms, studies have been mixed with some showing improvement but others showing no effect. If you suffer from psoriasis, you may want to try a fish oil supplement, or else I highly recommend that you make sure to have fish rich in omega-3s regularly.
The bottom line of all that is that there was no clear health benefit from consuming omega-3 fatty acids in food or supplements. There was a suggestion of a possible benefit from LCn3 on cardiac events, but this did not hold up when they took into consideration the quality of the evidence. The better trials, with less risk of bias, tended to be negative.
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.
Healthy cells require a delicate balance of EPA and DHA and the body employs clever mechanisms to support this natural equilibrium. DHA levels are self-regulated through inhibiting the activity of the enzyme delta-6 desaturase – the very enzyme that supports the conversion of EPA into DHA – to ensure levels of DHA do not become too high. It is therefore possible to have too much preformed DHA, if our supplement intake exceeds the body’s needs.
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.
The chemical structure of eicosapentaenoic acid and docosahexaenoic acid. Eicosapentaenoic acid consists of 20 carbons (C20) with 5 double bonds, and the last unsaturated carbon is located third from the methyl end (n-3). Do-cosahexaenoic acid consists of 22 carbons (C22) with 6 double bonds, and also with the3 last unsaturated carbon located third from the methyl end (n-3). Adapted with permission from Frishman et al, eds. Cardiovascular Pharmacotherapeutics. New York, NY: McGraw Hill; 2003.3
The deficiency of EPA and DHA in diet contributes to skin conditions, such as dandruff, thinning hair, eczema and psoriasis, as well as age spots and sun spots. Without the essential fatty acids, too much moisture leaves the skin. The truth is your internal health can appear on your skin, and taking fish oil internally as a supplement may be as good as or better than applying conventional moisturizers.
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Consumers of oily fish should be aware of the potential presence of heavy metals and fat-soluble pollutants like PCBs and dioxins, which are known to accumulate up the food chain. After extensive review, researchers from Harvard's School of Public Health in the Journal of the American Medical Association (2006) reported that the benefits of fish intake generally far outweigh the potential risks.

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!
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:
Sekikawa, A., Curb, D., Ueshima, H., El-Saed, A., Kadowaki, T., Abbott, R. D., ... Kuller, L. H. (2008 August 5). Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese Americans, and Whites: a cross-sectional study. Journal of the American College of Cardiology 52(6), 417–424. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736602/
Joensen, A. M., Schmidt, E. B., Dethlefsen, C., Johnsen, S. P., Tjonneland, A., Rasmussen, L. H., and Overvad, K. Dietary intake of total marine n-3 polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid and docosapentaenoic acid and the risk of acute coronary syndrome - a cohort study. Br J Nutr 2010;103(4):602-607. View abstract.

Humans can convert short-chain omega−3 fatty acids to long-chain forms (EPA, DHA) with an efficiency below 5%.[73][74] The omega−3 conversion efficiency is greater in women than in men, but less studied.[75] Higher ALA and DHA values found in plasma phospholipids of women may be due to the higher activity of desaturases, especially that of delta-6-desaturase.[76]


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.


Krill oil is a source of omega−3 fatty acids.[116] The effect of krill oil, at a lower dose of EPA + DHA (62.8%), was demonstrated to be similar to that of fish oil on blood lipid levels and markers of inflammation in healthy humans.[117] While not an endangered species, krill are a mainstay of the diets of many ocean-based species including whales, causing environmental and scientific concerns about their sustainability.[118][119][120]
My initial interest in omga-3 was an article by Dr Andrew Stoll in Harvard about May 99, One of my bipolar patients had extreme OCD related to HIV which was not relevant to her. I put her on 9.6g of fish oil and continued her on her regular medication. She was well for the next 3 years with no obvious mental health problem when she was attending here.
Ample evidence from animal studies supports regular supplementation with omega-3 oils as a means of lowering long-term cardiovascular risk. This may be due to omega-3 fatty acids’ effects on reducing inflammation, lowering triglycerides, reducing blood pressure, improving endothelial function, inducing new blood vessel formation after heart attack or stroke, and favorable modification of obesity-related inflammatory molecules.35-39
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This constant sweeping motion of DHA also causes the breakup of lipid rafts in membranes (8). Disruption of these islands of relatively solid lipids makes it more difficult for cancer cells to continue to survive and more difficult for inflammatory cytokines to initiate the signaling responses to turn on inflammatory genes (9). In addition, the greater spatial characteristics of DHA increase the size of LDL particles to a greater extent compared to EPA. As a result, DHA helps reduce the entry of these enlarged LDL particles into the muscle cells that line the artery thus reducing the likelihood of developing atherosclerotic lesions (10). Thus the increased spatial territory swept out by DHA is good news for making certain areas of membranes more fluid or lipoprotein particles larger, even though it reduces the benefits of DHA in competing with AA for key enzymes important in the development of cellular inflammation.
Several recent clinical studies, especially those focusing on the benefits of omega-3 in inflammatory conditions, have investigated the actions of pure-EPA in protecting against excess inflammation in the body. EPA works in several different ways. Firstly, it is the precursor to a number of immune messengers, collectively called ‘eicosanoids’ (series-3 prostaglandins, series-3 thromboxanes and series-5 leukotrienes,) all of which have anti-inflammatory roles.
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.
Matsumura  K, Noguchi  H, Nishi  D, Hamazaki  K, Hamazaki  T, Matsuoka  YJ.  Effects of omega-3 polyunsaturated fatty acids on psychophysiological symptoms of post-traumatic stress disorder in accident survivors: a randomized, double-blind, placebo-controlled trial.  J Affect Disord. 2017;224:27-31. doi:10.1016/j.jad.2016.05.054PubMedGoogle ScholarCrossref
The three types of omega−3 fatty acids involved in human physiology are α-linolenic acid (ALA), found in plant oils, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both commonly found in marine oils.[2] Marine algae and phytoplankton are primary sources of omega−3 fatty acids. Common sources of plant oils containing ALA include walnut, edible seeds, clary sage seed oil, algal oil, flaxseed oil, Sacha Inchi oil, Echium oil, and hemp oil, while sources of animal omega−3 fatty acids EPA and DHA include fish, fish oils, eggs from chickens fed EPA and DHA, squid oils, and krill oil. Dietary supplementation with omega−3 fatty acids does not appear to affect the risk of death, cancer or heart disease.[4][5] Furthermore, fish oil supplement studies have failed to support claims of preventing heart attacks or strokes or any vascular disease outcomes.[6][7]
Since EPA and DHA are both essential for health and appear together in nature, many studies have attempted to treat clinical conditions with combined EPA and DHA oils, but the outcomes have been varied, contradictory and disappointing. Consequently, researchers have started to investigate the individual actions of EPA and DHA in isolation, in numerous health conditions where an omega-3 deficiency is related to symptoms or known to play a causative role. The emerging evidence shows marked differences between how these two fatty acids affect us – not just at the cellular level but also the body as a whole.
The question is whether the observed cardiovascular benefits often found among fish eaters is due solely to the oils in fish or to some other characteristics of seafood or to still other factors common to those who eat lots of fish, like eating less meat or pursuing a healthier lifestyle over all. Whatever the answer, it does not seem to be fish oil supplements.

Humans can convert short-chain omega−3 fatty acids to long-chain forms (EPA, DHA) with an efficiency below 5%.[73][74] The omega−3 conversion efficiency is greater in women than in men, but less studied.[75] Higher ALA and DHA values found in plasma phospholipids of women may be due to the higher activity of desaturases, especially that of delta-6-desaturase.[76]
Jump up ^ Kwak SM, Myung SK, Lee YJ, Seo HG (May 2012). "Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials". Archives of Internal Medicine. 172 (9): 686–94. doi:10.1001/archinternmed.2012.262. PMID 22493407.
Jump up ^ Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J (July 2006). "n−3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review". The American Journal of Clinical Nutrition. 84 (1): 5–17. doi:10.1093/ajcn/84.1.5. PMID 16825676.

Funding/Support: The work was supported in part by grant 17H04253, Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science; grant 30-A-17 from the National Cancer Center Research and Development Fund; grants MOST106-2314-B-039-027-MY, 106-2314-B-038-049, 106-2314-B-039-031, 106-2314-B-039-035, 104-2314-B-039-022-MY2, and 104-2314-B-039-050-MY3 from the Ministry of Science and Technology, Taiwan; grant HRI-EX105-10528NI from the National Health Research Institutes, Taiwan; and grants CRS-106-063, DMR-107-202, and DMR-107-204 from the China Medical University, Taiwan.


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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).

Yamagishi, K., Iso, H., Date, C., Fukui, M., Wakai, K., Kikuchi, S., Inaba, Y., Tanabe, N., and Tamakoshi, A. Fish, omega-3 polyunsaturated fatty acids, and mortality from cardiovascular diseases in a nationwide community-based cohort of Japanese men and women the JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study. J.Am.Coll.Cardiol. 9-16-2008;52(12):988-996. View abstract.
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