Highlights
- Omega-3 fatty acids are essential fats that our bodies cannot make
- Taking high levels of the omega-3 fats DHA and EPA (460 mg EPA and 380 mg DHA in two large trials) was associated with reduced risk of cardiovascular disease and possibly cancer
One of the most common supplements taken by people besides a daily multivitamin. Clinical evidence indicates that Omega-3 fat intake is associated with lowering heart attack and cardiovascular deaths.
The biology
Omega-3 fatty acids are so-called long chain polyunsaturated fatty acids that our bodies cannot make. So we need to take these in from food or supplements. But why should we take these omega-3 fatty acids? What is the benefit? Large scale clinical trials have now shown that raising blood levels of two Omega three fatty acids: EPA and DHA are associated with reduced risk of certain chronic diseases, specifically cardiovascular disease and possibly cancer. With that brief introduction I will jump right into the clinical evidence.
Clinical evidence
Two early clinical studies from 1989 and 1999 supported the hypothesis that omega-3 fatty acids are protective against a range of cardiovascular disease. A Japanese study from 2007 further demonstrated that omega-3 fatty acids reduce the risk of heart disease in particular in people with a history of coronary artery disease. However, there were also several trials that failed to show positive cardiovascular outcomes from Omega-3 supplementation.
Fortunately, since that time there have been 3 large clinical trials that have shown positive cardiovascular benefits. Two of these studies named VITAL and ASCEND gave 1 gm per day of Omega-3 formulation (460 mg EPA and 380 mg DHA), recruited men over 50 and women over 55 with no heart attack, stroke or cancer. ASCEND included adults over 40 years with diabetes but no cardiovascular disease. In both of these studies the total number of cardiovascular events were the same regardless of whether people took the supplements or not. But there was an important difference: in the vital study people who took the supplements experienced a 28% reduction in the rates of heart attack, while in the ascend study people who took the supplement had a 19% reduced risk of cardiovascular death. There was another study called REDUCE-IT where they recruited people with cardiovascular disease or with diabetes plus a cardiovascular risk factor. They were given 4 g per day of a modified form of EPA. This supplement reduced rates of overall cardiovascular events by an impressive 25%.
Supplementation
So the natural question is: what does it mean for me? How much should I take daily?
Guidelines for taking essential Omega-3 fatty acids:
We are careful to use the word ‘essential’ here. That’s because the food and nutrition board of The institute of medicine and academies considered alpha lipoic acid (ALA) as the only essential Omega-3 fatty acid. The reason for this is that a small percentage (about 15%) of ALA can be converted into DHA and EPA in the human liver. So it has only established guidelines for intake of ALA and not DHA and EPA.
Adequate daily intake level (19 years or older):
- Men: 1.6 gram
- Women: 1.1 gram
Note that the FDA advices no more than 2gm/day of omage-3 supplement and no more than 3gm/day of total omega-3 intake
Food sources of Omega-3:
- ALA: flaxseed, soybean, canola oil, chia seeds and walnuts.
- EPA and DHA: cold water fatty fish such as salmon, mackerel, tuna, herring and sardines. But the fish don’t make DHA and EPA. They’re actually made by microalgae which are eaten by the phytoplanktons that the fish eat.
Dietary supplement sources of Omega-3 DHA and EPA:
- animal source: Fish oil, krill oil, cod liver oil
- vegetarian source: algal oil
What about mercury contamination in seafood? While fish have been found to contain various levels of methylmercury, dietary supplements have not been found to contain detectable levels of methyl Mercury since it is removed during the purification process.
Safety
While generally considered safe, there are some risks of Omega-3 supplements to consider. Mild adverse effects are the most frequently reported and include gastrointestinal discomforts. These can be reduced when the supplements are taken with food. Omega-3 fatty acids mostly in high doses exceeding 3 gm per day, may have antiplatelet effects that prolong bleeding time, although clinically significant bleeding is uncommon. So additional caution is warranted for folks taking anticoagulant or antiplatelet drugs. Also, chronic high-dose intake of fish oil may modestly increase the risk of atrial fibrillation (heart flutter). The FDA recommendation is to not exceed 3gm/day with no more than 2gm/day from supplements.
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Manson, J. E., Bassuk, S. S., & Buring, J. E. (2020, April). Principal Results of the VITamin D and OmegA-3 TriaL (VITAL) and Updated Meta-analyses of Relevant Vitamin D Trials. The Journal of Steroid Biochemistry and Molecular Biology. https://pmc.ncbi.nlm.nih.gov/articles/PMC7089819/
Hu, Y., Hu, F. B., & Manson, J. E. (2019, October 1). Marine Omega-3 Supplementation and Cardiovascular Disease: An Updated Meta-Analysis of 13 Randomized Controlled Trials Involving 127,477 Participants. Journal of the American Heart Association. https://pmc.ncbi.nlm.nih.gov/articles/PMC5971211/
Bhatt, D. L., Steg, P. G., Brinton, E. A., Jacobson, T. A., Miller, M., Tardif, J. C., Ketchum, S. B., Doyle, R. T., Jr., Murphy, S. A., Soni, P. N., Braeckman, R. A., Juliano, R. A., & Ballantyne, C. M. (2017, March). Rationale and design of REDUCE‐IT: Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial. Clinical Cardiology. https://pmc.ncbi.nlm.nih.gov/articles/PMC5396348/
Fish oil. Mayo Clinic. https://www.mayoclinic.org/drugs-supplements-fish-oil/art-20364810
Krupa, K. N., Fritz, K., & Parmar, M. (2025). Omega-3 Fatty Acids. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK564314/