16. Saito Y, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, et al. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis. 2008;200:135–40. [PubMed]
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Various scales were used in these studies to evaluate the target outcome of anxiety symptoms: the Yale-Brown Obsessive-Compulsive Scale, Profile of Mood States, State-Trait Anxiety Inventory, Hamilton Anxiety Rating Scale, Generalized Anxiety Disorder questionnaire, Depression, Anxiety, and Stress Scales, Clinician-Administered Posttraumatic Stress Disorder Scale, Beck Anxiety Inventory, visual analog scale of anxiety, Impact of Event Scale–Revised, Conners score anxiety subscale, Neuropsychiatric Inventory, test anxiety severity, Hospital Anxiety and Depression Scale anxiety subscale, and Child Behavior Checklist anxiety subscale. The psychiatric and physical health conditions of the recruited participants also varied widely: general population without specific clinical conditions,36,47,51,55,60 participants with acute myocardial infarction,35 borderline personality disorder,2 mild to severe depression,59 obsessive-compulsive disorder,33 severe accidental injury,49 participants who were traumatized by disaster,54 participants with substance abuse disorder,34 women with premenstrual syndrome,56 children with attention-deficit/hyperactivity disorder,48,53 Alzheimer disease,58 generally healthy undergraduate college students but with test anxiety,61 Parkinson disease,52 and participants with Tourette syndrome.57 Sixteen studies compared the effect of omega-3 PUFA treatment with that of the placebo33,34,36,47-49,51-53,55-61; the other 3 studies were non–placebo controlled trials.35,50,54 The mean (SD) Jadad score of the recruited studies was 3.8 (1.0) (eTable in the Supplement).
Recently another Omega-3 fatty acid, DPA (Docosapentaenoic Acid) has been discussed more frequently in the scientific community, as a new and very potent Omega-3 fatty acid. Previously thought to work in through EPA and DHA we are now learning it has very distinct functions in the body. All three of these polyunsaturated fats play an important role in the functioning of our bodies.
Under these conditions, it may make sense to try fish oil even at higher doses than what I recommended. There is some evidence that krill oil will get the omega-3 fatty acids better into the brain in the psychiatric conditions that I listed. And there is some evidence that EPA-rich fish oils are better than DHA-rich fish oils for some of those psychiatric conditions as well. So there’s room to play around with the different possibilities if those things apply to you. But for the average case, limit the fish oil to 250 milligrams of EPA and DHA combined when you take it, but in all cases, go for food first, and go for fish oil only after you have exhausted those possibilities.
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.
Omega 3 fatty acids are monounsaturated fats that come from food sources—primarily cold water fish (eg, salmon, trout, tuna, mackerel, and herring)—that contain EPA (eicosapentaenoic acid) and docosahexaenoic acid (DHA). Other fatty acids are derived from plant-derived sources of food—including nuts (especially walnuts) and seeds (eg, flax, chia, sunflower)—that have primarily ALA (alpha-linolenic acid).
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.
Several large trials have evaluated the effect of fish or fish oils on heart disease. In the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardio (known as the GISSI Prevention Trial), heart attack survivors who took a 1-gram capsule of omega-3 fats every day for three years were less likely to have a repeat heart attack, stroke, or die of sudden death than those who took a placebo. (2) Notably, the risk of sudden cardiac death was reduced by about 50 percent. In the more recent Japan EPA Lipid Intervention Study (JELIS), participants who took EPA plus a cholesterol-lowering statin were less likely to have a major coronary event (sudden cardiac death, fatal or nonfatal heart attack, unstable angina, or a procedure to open or bypass a narrowed or blocked coronary artery) than those who took a statin alone. (3)
Macchia, A., Levantesi, G., Franzosi, M. G., Geraci, E., Maggioni, A. P., Marfisi, R., Nicolosi, G. L., Schweiger, C., Tavazzi, L., Tognoni, G., Valagussa, F., and Marchioli, R. Left ventricular systolic dysfunction, total mortality, and sudden death in patients with myocardial infarction treated with n-3 polyunsaturated fatty acids. Eur.J.Heart Fail. 2005;7(5):904-909. View abstract.
4. Omega-3 has been found to save the lives of children going through short bowel syndrome (SBS), which is uncommon but impacts thousands of people in the United States. SBS can occur from birth (when a portion of the intestine fails to develop) or due to an infectious inflammatory disease striking premature newborns. In adults, it can be caused by surgery for Crohn's disease or injury.
McNamara, R. K., Able, J., Jandacek, R., Rider, T., Tso, P., Eliassen, J. C., Alfieri, D., Weber, W., Jarvis, K., DelBello, M. P., Strakowski, S. M., and Adler, C. M. Docosahexaenoic acid supplementation increases prefrontal cortex activation during sustained attention in healthy boys: a placebo-controlled, dose-ranging, functional magnetic resonance imaging study. Am J Clin Nutr 2010;91(4):1060-1067. View abstract.
In addition to depression, chronic stress leads to loss of volume of the hippocampus—and also causes enlargement of the amygdala, the portion of the brain that regulates anxiety and anger.24 When rats were supplemented with omega-3s during exposure to stress, they showed lower corticosterone levels (a marker of stress), and improved learning on a maze—indicating that the omega-3s helped preserve memory and reduce anxiety.24

However, the researchers do have some good news. They concluded that omega 3 fatty acids do appear to reduce the type of blood cholesterol known as triglycerides, but that supplements probably are not useful for preventing or improving heart and circulatory problems. And, upping your intake of plant-based omega 3s high in ALA (ie, walnuts, flaxseed and flax oil, chia seeds) may help your heart somewhat.2


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.
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 seems that infancy and childhood are some of the most important periods of time in a person’s life to get plenty omega-3s in their diet, probably because of the amount of long-chain fatty acids found in the brain and retina. It’s crucial for developing babies and children to get a good amount of DHA and EPA so their brains and eyes develop fully and properly. (78)
There is, however, significant difficulty in interpreting the literature due to participant recall and systematic differences in diets.[53] There is also controversy as to the efficacy of omega−3, with many meta-analysis papers finding heterogeneity among results which can be explained mostly by publication bias.[54][55] A significant correlation between shorter treatment trials was associated with increased omega−3 efficacy for treating depressed symptoms further implicating bias in publication.[55]
Findings  In this systematic review and meta-analysis of 19 clinical trials including 2240 participants from 11 countries, improvement in anxiety symptoms was associated with omega-3 polyunsaturated fatty acid treatment compared with controls in both placebo-controlled and non–placebo-controlled trials. The anxiolytic effects of omega-3 polyunsaturated fatty acids were also stronger in participants with clinical conditions than in subclinical populations.

Hanwell, H. E., Kay, C. D., Lampe, J. W., Holub, B. J., and Duncan, A. M. Acute fish oil and soy isoflavone supplementation increase postprandial serum (n-3) polyunsaturated fatty acids and isoflavones but do not affect triacylglycerols or biomarkers of oxidative stress in overweight and obese hypertriglyceridemic men. J Nutr 2009;139(6):1128-1134. View abstract.


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.
Evidence in the population generally does not support a beneficial role for omega−3 fatty acid supplementation in preventing cardiovascular disease (including myocardial infarction and sudden cardiac death) or stroke.[4][19][20][21] A 2018 meta-analysis found no support that daily intake of one gram of omega-3 fatty acid in individuals with a history of coronary heart disease prevents fatal coronary heart disease, nonfatal myocardial infarction or any other vascular event.[6] However, omega−3 fatty acid supplementation greater than one gram daily for at least a year may be protective against cardiac death, sudden death, and myocardial infarction in people who have a history of cardiovascular disease.[22] No protective effect against the development of stroke or all-cause mortality was seen in this population.[22] Eating a diet high in fish that contain long chain omega−3 fatty acids does appear to decrease the risk of stroke.[23] Fish oil supplementation has not been shown to benefit revascularization or abnormal heart rhythms and has no effect on heart failure hospital admission rates.[24] Furthermore, fish oil supplement studies have failed to support claims of preventing heart attacks or strokes.[7]
Dry eye disease occurs when tears don’t provide enough moisture, causing eye discomfort and vision problems. Some studies show that getting more omega-3s from foods or supplements—mainly EPA and DHA—helps relieve symptoms of dry eye disease. But a large, recent study found that the symptoms of people with dry eye disease who took fish oil supplements of 2,000 mg EPA plus 1,000 mg DHA daily for 1 year did not improve any more than those who took a placebo (a dummy pill). More research on the effects of omega-3s on dry eye disease is needed.
Evidence linking fish oil and cancer has been all over the map. Some research suggests diets high in fatty fish or fish oil supplements might reduce the risk of certain cancers, including prostate cancer. Other research shows just the opposite, a  link between eating a lot of oily fish or taking potent fish oil supplements and a 43% increased risk for prostate cancer overall, and a 71% increased risk for aggressive prostate cancer.
EPA is the precursor to DHA in the body and can be converted to DHA with the enzyme delta-6 desaturase, but this process is inefficient in many people (much like the inefficiency of short-chain omega-3s to long-chain). For those individuals taking pure EPA products as well as those taking our EPA-rich products, we still recommend eating oily fish at least once each week to provide a natural source of DHA. Fish provides a unique nutritional package, supplying the diet with important amino acids (the building blocks of proteins) and antioxidants, including vitamins and minerals needed to process fats, so eating fish will also support the natural enzyme-dependent EPA to DHA conversion.
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!
Two psychiatrists (P.-T.T. and T.-Y.C.) separately performed a systematic literature search of the PubMed, Embase, ProQuest, ScienceDirect, Cochrane Library, ClinicalKey, Web of Science, and ClinicalTrials.gov databases to March 4, 2018. Because we presumed some clinical trials would use investigating scales for some other mood symptoms but also contain symptoms of anxiety, we tried to use some nonspecific medical subject heading terms to include those clinical trials. Therefore, we used the following keywords: omega-3, eicosapentaenoic acid, EPA, DHA, or docosahexaenoic acid; and anxiety, anxiety disorder, generalized anxiety disorder, agoraphobia, panic disorder, or posttraumatic stress disorder. After removing duplicate studies, the same 2 authors screened the search results according to the title and abstract to evaluate eligibility. List of potentially relevant studies were generated for a full-text review. Any inconsistencies were discussed with a third author to achieve final consensus. To expand the list of potentially eligible articles, we performed a manual search of the reference lists of review articles in this area.12,38,39
A Cochrane meta-analysis published in June 2012 found no significant protective effect for cognitive decline for those aged 60 and over and who started taking fatty acids after this age. A co-author of the study said to Time, "Our analysis suggests that there is currently no evidence that omega-3 fatty acid supplements provide a benefit for memory or concentration in later life".[43]

Fish Oil capsules contain omega-3 polyunsaturated fatty acids. Omega-3 polyunsaturated fatty acids are found in oils from certain types of fish, vegetables, and other plant sources. These fatty acids are not made by the body and must be consumed in the diet. Omega-3 polyunsaturated fatty acids work by lowering the body's production of triglycerides. High levels of triglycerides can lead to coronary artery disease, heart disease, and stroke.


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/
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).
Some studies suggest that people who get higher amounts of omega-3s from foods and dietary supplements may have a lower risk of breast cancer and perhaps colorectal cancer. More research is needed to confirm this possible link. Whether omega-3s affect the risk of other cancers is not clear. Clinical trials to examine this possibility are in progress.
These conversions occur competitively with omega−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. They both utilize the same desaturase and elongase proteins in order to synthesize inflammatory regulatory proteins.[50] The products of both pathways are vital for growth making a balanced diet of omega−3 and omega−6 important to an individual's health.[77] A balanced intake ratio of 1:1 was believed to be ideal in order for proteins to be able to synthesize both pathways sufficiently, but this has been controversial as of recent research.[78]

Agency for Healthcare Research and Quality. Effects of Omega-3 Fatty Acids on Lipids and Glycemic Control in Type II Diabetes and the Metabolic Syndrome and on Inflammatory Bowel Disease, Rheumatoid Arthritis, Renal Disease, Systemic Lupus Erythematosus, and Osteoporosis. AHRQ Publication No. 04-E012-1; 2004. Available at: https://archive.ahrq.gov/downloads/pub/evidence/pdf/o3lipid/o3lipid.pdf. (Accessed February 7, 2017).
Heavy metal poisoning by the body's accumulation of traces of heavy metals, in particular mercury, lead, nickel, arsenic, and cadmium, is a possible risk from consuming fish oil supplements.[medical citation needed] Also, other contaminants (PCBs, furans, dioxins, and PBDEs) might be found, especially in less-refined fish oil supplements.[citation needed] However, heavy metal toxicity from consuming fish oil supplements is highly unlikely, because heavy metals selectively bind with protein in the fish flesh rather than accumulate in the oil. An independent test in 2005 of 44 fish oils on the US market found all of the products passed safety standards for potential contaminants.[107][unreliable source?]

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.

Throughout their history, the Council for Responsible Nutrition and the World Health Organization have published acceptability standards regarding contaminants in fish oil. The most stringent current standard is the International Fish Oils Standard.[108][non-primary source needed] Fish oils that are molecularly distilled under vacuum typically make this highest-grade; levels of contaminants are stated in parts per billion per trillion.[citation needed][109]

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]
The two key omega-3 fatty acids are docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Fatty fish like salmon, mackerel, and sardines are rich in these omega-3s. Some plants are rich in another type of omega-3 fatty acid, alpha-linolenic acid, which the body can convert to DHA and EPA. Good sources of these are flaxseeds, chia seeds, walnuts, pumpkin seeds, and canola oil.
A 2014 meta-analysis of eleven trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and of eight trials with patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo. The study concluded that: "The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD."[42]

A certain kidney disease called IgA nephropathy. Some research shows that long-term but not short-term use of fish oil can slow the loss of kidney function in high-risk patients with IgA nephropathy. Fish oil might have greater effects when taken at higher doses. Also, it might be most effective in people with IgA nephropathy who have higher levels of protein in the urine.
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