EPA (20:5n-3) is a 20-carbon omega-3 that: (1) COMPETES with arachidonic acid (AA, 20:4n-6) for membrane phospholipid incorporation, higher EPA:AA ratio = less inflammatory substrate available; (2) is converted by COX-2 into PGE3 (weakly inflammatory) instead of PGE2 (strongly inflammatory); (3) is converted by 5-LOX into LTB5 (weakly chemotactic) instead of LTB4 (strongly chemotactic); (4) is converted by 15-LOX into resolvin E1/E2, specialized pro-resolving mediators (SPMs) that actively promote inflammation RESOLUTION (clearing neutrophils, stimulating macrophage efferocytosis); (5) suppresses NF-κB activation via GPR120 receptor. For depression: EPA reduces neuroinflammation (microglial activation) and increases BDNF, both mechanisms relevant to depression pathophysiology.
Based on independent third-party laboratory analysis
Category pass rate: ~90% of fish oil products passed content testing. Rancidity is the primary failure mode — ~10% of products are already oxidized before opening.
Contamination risk: MODERATE. All tested products passed heavy metal testing. Mercury, lead, cadmium all below detection limits. Fish oil purification processes (molecular distillation) effectively remove contaminants.
Independently graded against 178,763 indexed supplements and 757 reviewed supplement and medication pairs, sourced from PubMed, FDA CAERS, openFDA, and NIH DSLD | Last updated:
Not medical advice. Based on published clinical research and systematic reviews.
Safety
Warfarin (Coumadin)
Concurrent use of fish oil and anticoagulants like warfarin can increase the International Normalized Ratio (INR) and elevate the risk of bleeding.
Omega-3 fatty acids in fish oil can inhibit platelet aggregation and reduce the levels of vitamin K-dependent coagulation factors. This potentiates the anticoagulant effects of medications like warfarin.
A longer bleeding time is reported at 2 to 15 g a day of EPA and DHA combined. No upper limit has been set. The bleeding concern matters most if you take a blood thinner.
Moderate-dose omega-3 (under 3 g per day) generally safe with warfarin per published data. High doses may require INR monitoring.
EPA and DHA at over 3 g per day mildly inhibit thromboxane A2 synthesis. Mixed evidence on INR shift with warfarin.
SourcePMID 25062404
Clopidogrel (Plavix)
A longer bleeding time is reported at 2 to 15 g a day of EPA and DHA combined. No upper limit has been set. The bleeding concern matters most if you take a blood thinner.
Observational additive bleeding risk. Monitor closely.
Omega-3 fish oil high-dose additive antiplatelet effect with clopidogrel.
High-dose Aspirin
Mild bleeding risk increase.
Additive antiplatelet effects via different mechanisms. Generally safe at standard doses.
A longer bleeding time is reported at 2 to 15 g a day of EPA and DHA combined. No upper limit has been set. The bleeding concern matters most if you take a blood thinner.
Omega-3 fish oil high-dose may add to the bleeding risk of Aspirin. No study examines this pair; the supplement evidence was gathered with aspirin or warfarin. Tell your clinician you take both and stop the supplement before surgery.
Omega-3 fish oil high-dose has antiplatelet activity that is observationally additive to aspirin.
Blood pressure medications
Beneficial cardiovascular combination. Mild additive BP lowering at high doses (>3 g/day EPA+DHA).
Omega-3 fatty acids (EPA/DHA) modestly lower blood pressure and reduce vascular inflammation. Generally complementary with Lisinopril.
Beneficial cardiovascular combination. Mild additive BP lowering at high doses (>3 g/day EPA+DHA).
Omega-3 fatty acids (EPA/DHA) modestly lower blood pressure and reduce vascular inflammation. Generally complementary with Losartan.
Beneficial cardiovascular combination. Mild additive BP lowering at high doses (>3 g/day EPA+DHA).
Omega-3 fatty acids (EPA/DHA) modestly lower blood pressure and reduce vascular inflammation. Generally complementary with Ramipril.
Beneficial cardiovascular combination. Mild additive BP lowering at high doses (>3 g/day EPA+DHA).
Omega-3 fatty acids (EPA/DHA) modestly lower blood pressure and reduce vascular inflammation. Generally complementary with Valsartan.
Orlistat (Alli)
Stop 2 weeks before surgery
Bleeding risk from antiplatelet effect.
Educational information only. This is not medical advice. These statements have not been evaluated by the FDA. Talk to your prescriber before starting, stopping, or combining any supplement with prescription medication.