Omega-3 Fish Oil (EPA/DHA)
Fish oil supplies EPA and DHA, omega-3 fats found in fish. It lowers triglycerides. For heart attacks and strokes, results are mixed: one major trial of high-dose prescription EPA found a benefit, two others didn't, and the American Heart Association doesn't recommend omega-3 supplements for people without high heart-disease risk. It may slightly help joint pain in rheumatoid arthritis. A Cochrane review found a small effect on depressive symptoms but rated the evidence very low certainty.
Omega-3 fish oil supplies EPA and DHA, omega-3 fats found in fish, fish oils and krill oils. Omega-3s are part of the structure of cell membranes throughout the body, and DHA is especially concentrated in the retina, brain and sperm.
Research & evidence
Strong support Some support Weak or no supportColours show how well the sources back each point. The reason is next to each one.
A 2021 Cochrane review found a small-to-modest reduction in depressive symptoms with omega-3 supplementation compared to placebo (SMD -0.40, 33 studies, 1,848 participants), but rated this result very low certainty and stated the effect size is "unlikely to be clinically meaningful."
Limited evidenceSome support. Reviewers rated the certainty low
Study details
Cochrane rated this result very low certainty. Its evidence base is omega-3 vs. placebo (34 studies, 1,924 participants; 33 of them, with 1,848 participants, supplied data for the depressive-symptom result above). Only one small study (40 people) directly compared omega-3 with antidepressants, with imprecise, inconclusive results. The authors state that their estimate "may be biased towards a positive finding," based on sensitivity analyses, funnel plot inspection and comparison with large, well-conducted trials.
Source: Appleton KM, Sallis HM, Perry R, et al. "Omega-3 fatty acids for depression in adults." Cochrane Database Syst Rev. 2021 Nov 24;11(11):CD004692. View source
Omega-3 fatty acids can reduce triglyceride levels.
Strong evidenceStrong support. Stated plainly by NIH or an FDA label
Study details
Triglycerides: across 58 trials, each 1 g/day increase in long-chain omega-3 reduced triglycerides by 5.9 mg/dL.
Source: NIH Office of Dietary Supplements, Omega-3 Fatty Acids — Health Professional Fact Sheet. View source
For heart attacks and strokes, results are mixed: REDUCE-IT, a trial of high-dose prescription EPA in high-risk patients, found a benefit, but a 12,536-person trial of 1 g/day and the Alpha Omega Trial in heart-attack survivors did not. The American Heart Association does not recommend omega-3 supplements for people without high cardiovascular risk.
Mixed evidenceSome support. Results are mixed
Study details
Heart outcomes: REDUCE-IT (4 g/day prescription EPA-only, high-risk patients) found significant benefit, but two other major trials — a ~6-year, 1 g/day trial (12,536 people) and the 40-month Alpha Omega Trial (4,837 post-MI patients) — found triglycerides dropped significantly with no reduction in myocardial infarction, stroke or cardiovascular death. NIH ODS states the AHA does not recommend omega-3 supplements for people without high cardiovascular risk.
Source: NIH Office of Dietary Supplements, Omega-3 Fatty Acids — Health Professional Fact Sheet. View source
Omega-3s may slightly reduce joint pain in rheumatoid arthritis; for osteoarthritis the evidence is weaker and not statistically significant.
Moderate evidenceSome support. Shown only in certain groups, uses, strains or doses
Study details
Moderate-quality evidence for pain in rheumatoid arthritis (SMD -0.21, 22 trials); low-quality and not statistically significant for osteoarthritis (5 trials). An inflammation marker (CRP, 25 trials) showed a small effect (SMD -0.28, low-quality evidence). The one function outcome measured (grip strength/walk tests) showed essentially no effect (SMD -0.01, moderate-quality evidence). The osteoarthritis results varied widely between trials (I2=82%).
Source: Senftleber NK, Nielsen SM, Andersen JR, et al. "Marine Oil Supplements for Arthritis Pain: A Systematic Review and Meta-Analysis of Randomized Trials." Nutrients. 2017 Jan 6;9(1):42. View source
Dosage
| Form | Amount |
|---|---|
| Any form | There's no official recommended amount of EPA or DHA. A typical fish oil supplement provides about 1,000 mg of fish oil containing 180 mg EPA and 120 mg DHA, but doses vary widely. Algal oil (vegetarian) products usually provide about 100–300 mg DHA, and some contain EPA as well. The FDA considers up to 5 g a day of EPA and DHA from supplements safe when used as recommended. |
Side effects
Well documented Reported (case reports, anecdotal or one study) None reportedThe circle shows how well documented an effect is, not how serious it is. A rarely reported effect can still be serious, so always read ‘When to stop’.
| Effect | Frequency | When to stop |
|---|---|---|
| Fishy taste, burping, gas, bad breathWell documentedListed plainly by NIH, MSK or LiverTox | Commonly reported; usually mild | Stop and talk to a doctor if it persists or bothers you. |
| Diarrhea, nausea, heartburn, stomach discomfortWell documentedListed plainly by NIH, MSK or LiverTox | Commonly reported; usually mild | Stop and talk to a doctor if it persists. |
Safety & interactions
Safety
Side effects of omega-3 supplements are usually mild: unpleasant taste, bad breath, heartburn, nausea, stomach discomfort, diarrhea, headache, and smelly sweat. The FDA considers supplements providing up to 5 g a day of EPA and DHA safe when used as recommended. Doses of 2–15 g a day might increase bleeding time, and taking 4 g a day for several years slightly increased the risk of atrial fibrillation in people with heart disease or at high risk of it (see Drug interactions).
Contraindications
MSK says not to take omega-3 if you take blood thinners, because it can increase your risk of bleeding, or glucocorticoids, because it can worsen some of their side effects — see Drug interactions. MSK lists no other contraindications. If you have a fish or shellfish allergy, check the label to see what the oil is made from.
Drug interactions
Fish oil can prolong clotting times — shown as an elevated INR — when taken with warfarin, and case reports document elevated INR at doses as low as 2 g/day and a subdural hematoma at 6 g/day (MSK). That said, NIH ODS notes most research finds doses of 3–6 g/day do not significantly affect anticoagulant status, a 2014 review found no effect on clinically significant bleeding, and FDA-approved package inserts for omega-3 pharmaceuticals report no clinically significant bleeding episodes. Those same package inserts still direct that patients taking omega-3s with anticoagulants be monitored periodically for changes in INR — and MSK's patient guidance is not to combine them at all. If you take warfarin or another anticoagulant, talk to your prescriber before starting fish oil.
MSK's patient page says: "Don't take omega-3 if you're taking blood thinners such as aspirin, heparin, warfarin (Coumadin, Jantoven), clopidogrel (Plavix), apixaban (Eliquis), or rivaroxaban (Xarelto)... Omega-3 can increase your risk of bleeding." MSK's professional section has no separate entry for aspirin or clopidogrel. NIH doesn't list this interaction, but notes that fish oil "can have antiplatelet effects at high doses, although it appears to be less potent than aspirin," and cites an IOM assessment that "doses of 2-15 g/day EPA and/or DHA might also increase bleeding time by reducing platelet aggregation."
In a mouse study, omega-3 supplements made some side effects of glucocorticoids worse; MSK says the clinical relevance in humans is not known. MSK's patient page still says: "Don't take omega-3 if you're taking glucocorticoids, such as cortisone, hydrocortisone or dexamethasone. Omega-3 supplements can worsen some side effects caused by glucocorticoids."
Not a drug interaction, but a dose-related risk: NIH ODS reports that two large clinical trials found that taking 4 g/day of omega-3 supplements for several years slightly increased the risk of atrial fibrillation in people with CVD or at high risk of CVD. A typical fish oil supplement provides about 300 mg of EPA and DHA combined (180 mg EPA and 120 mg DHA, per NIH).
Established: stated plainly by an authoritative source. Documented: supported by case reports or trial data. Theoretical: based on mechanism, animal data, or a cautious listing. Always check with your pharmacist or prescriber.
Which form to buy
Natural or re-esterified triglycerides, free fatty acids
Good choiceAbsorbed better than other forms (per NIH)
Somewhat better absorbed than ethyl esters, though every form raises blood EPA and DHA.
Ethyl esters
Works, with a catchWorks, but absorbed somewhat less than the leading form
Somewhat less absorbed than triglyceride forms, but still raises EPA and DHA. (The prescription drug in the REDUCE-IT trial is an ethyl ester.)
Krill oil (phospholipids)
Works, with a catchStudies disagree on whether it's better
Some studies find it's absorbed a bit better than fish oil; others don't.
Algal oil (plant-based)
Works, with a catchPlant-based; good absorption in one small study
A plant source, usually 100–300 mg DHA. In one small study its DHA was absorbed as well as DHA from cooked salmon.