Omega-3 fatty acids (fish oil)Fat

• Triglyceride loweringLikely helps

  This is the most consistent finding in the whole file. The 2020 Cochrane review of 86 RCTs (162,796 participants) found long-chain omega-3s lowered serum triglycerides by about 15% [1].
  
  The size of the drop scales with dose. Roughly 5–10% per 1 g/day of EPA+DHA per the National Lipid Association, versus 25–50% at prescription strength (3.4 g/day) within about a month [5][6].
  
  The mechanism reported is reduced liver output of triglyceride-rich VLDL particles [6]. Most trials measuring this outcome run 8–12 weeks or longer [5]. ^[1]

• Cardiovascular events at 4 g/dayPossibly helps

  REDUCE-IT and STRENGTH tested nearly the same dose and disagreed. REDUCE-IT (2019, 8,179 high-risk patients) found 4 g/day of prescription EPA-only icosapent ethyl cut a composite cardiovascular endpoint by 25% [1].
  
  STRENGTH (2020, 13,078 patients) found no significant benefit from 4 g/day of an EPA+DHA carboxylic acid product [1]. It also recorded more atrial fibrillation in the treatment arm than on placebo [1].
  
  The two used different omega-3 formulations and different placebo oils, mineral oil versus corn oil. Researchers read that as a partial explanation, not a settled one [1].
  
  The practical reading: a prescription EPA-only ester and a general EPA+DHA capsule are not interchangeable products, and this page does not average them into one verdict. ^[1]

• Overall cardiovascular riskPossibly helps

  The pooled evidence is weaker than the triglyceride effect and points in more than one direction.
  
  The 2020 Cochrane review found a slight reduction in cardiovascular mortality and coronary heart disease events, but no effect on all-cause mortality, overall cardiovascular events, stroke, or arrhythmia [1].
  
  A 2019 meta-analysis of 13 trials (127,477 participants), including VITAL and ASCEND, did find fewer heart attacks and less coronary heart disease death, apparently dose-related [1]. The same analysis found no significant reduction in stroke [1].
  
  Doses across those 13 trials ranged from 0.376 to 4 g/day, over a mean of about 5 years [1]. ^[1]

• Eating fish versus taking capsulesPossibly helps

  This is the field's most persistent disagreement, and nobody has resolved it.
  
  Observational studies consistently link seafood intake to lower cardiovascular risk. Supplement RCTs — ASCEND, VITAL, ORIGIN, the Alpha Omega Trial — have mostly returned null or mixed results for hard endpoints, especially in general or low-risk populations [1].
  
  The American Heart Association's position follows that split. It advises 1–2 fish servings a week for the general population, and does not recommend omega-3 supplements for people without high cardiovascular risk [1]. ^[1]

• Preterm birth risk in pregnancyLikely helps

  A 2018 Cochrane review of 70 RCTs (almost 20,000 women) found long-chain omega-3 supplementation lowered preterm birth risk by 11%, and early preterm birth before 34 weeks by 42% [1].
  
  A 2022 follow-up statement reported similar reductions [1]. The trials behind this used regular fish oil, not cod liver oil [12]. ^[1]

• Major depressive disorderPossibly helps

  A 2015 Cochrane review of 26 studies found insufficient evidence that omega-3 supplements at 1,000–6,600 mg/day meaningfully help major depressive disorder in adults [1].
  
  A 2021 review of 35 studies (1,964 participants) landed in the same place. Any effect is likely too small to be clinically meaningful, and it rated the evidence low to very low quality [4].
  
  This sits at unclear rather than fail because the underlying evidence is weak, not because a strong trial found nothing. ^[1]

• Dry eye diseaseNot shown to help

  The largest and most rigorous trial found nothing. The NIH-funded DREAM study (535 participants, 12 months) found omega-3 supplementation no better than placebo on dry eye symptoms or signs [1].
  
  A VITAL ancillary study following 23,523 people for a median 5.3 years found no effect on dry eye incidence or on severe symptoms [1].
  
  Several smaller trials did report symptom improvement, so the literature is not unanimous [1]. We mark this fail on the strength of the two largest studies, rather than pretending the smaller ones do not exist. ^[1]

• Rheumatoid arthritisPossibly helps

  Trials generally show patients leaning less on NSAIDs and corticosteroids, while effects on the joint symptoms themselves — pain, swelling, stiffness — stay inconsistent [1].
  
  A 2022 review of 30 studies found omega-3-rich diets may improve pain and swollen or tender joint counts as an adjunct to drug therapy [1]. That is alongside medication, not instead of it. ^[1]

• ADHD symptomsNot shown to help

  A 2023 Cochrane review of 36 studies found no consistent symptom improvement in ADHD [1].
  
  That is a large body of evidence pointing at no effect, which is a different situation from evidence simply being absent. ^[1]

• Maintaining remission in Crohn's diseaseNot shown to help

  A Cochrane review concluded omega-3 supplements are probably not effective for maintaining remission in Crohn's disease [1].
  
  NIH ODS does not support omega-3 supplements for inflammatory bowel disease more broadly [1]. ^[1]

• Cystic fibrosis lung functionPossibly helps

  A Cochrane review noted a possible lung-function benefit across doses of 300–5,400 mg/day EPA/DHA [1].
  
  It judged the evidence insufficient to recommend routine use [1]. ^[1]

• Rough, scaly skin and dermatitis — the classical sign of essential fatty-acid deficiency, whether omega-3 or omega-6
• Falling plasma and tissue DHA, with no established blood-level cutoff below which visual, neural, or immune problems are known to appear
• Almost only documented in patients on long-term intravenous nutrition lacking PUFAs, in case reports from the 1970s and 1980s
• Rare in the general US population — modern enteral and parenteral feeding formulas now contain adequate PUFA levels
• During ordinary fat restriction or malabsorption the body draws essential fatty acids from adipose stores, which limits how often overt deficiency develops^[1]

• Natural triglyceridesThe default in unconcentrated fish-body oils.

  Elemental content

  The form omega-3s occur in naturally inside fish oil

  Absorption

  Somewhat higher bioavailability than ethyl esters, per NIH's Office of Dietary Supplements [1].

  Best for

  The default in unconcentrated fish-body oils. All forms raise plasma EPA and DHA significantly, so this is a margin rather than a category difference [1].

• Ethyl estersConcentrated and prescription products.

  Elemental content

  Glycerol backbone swapped for ethanol, which allows more EPA/DHA per capsule

  Absorption

  The lowest bioavailability among the common forms, per NIH ODS.
  
  It still raises plasma EPA and DHA meaningfully [1].

  Best for

  Concentrated and prescription products. Icosapent ethyl — the 4 g/day EPA-only product used in REDUCE-IT — is an ethyl ester [1].

• Re-esterified triglycerides and free fatty acidsConcentrated products for someone who wants triglyceride-form absorption without the ethyl-ester gap .

  Elemental content

  Ethyl esters converted back into triglyceride form, or fatty acids supplied unbound

  Absorption

  Both sit with natural triglycerides, above ethyl esters, in NIH ODS's ranking [1].

  Best for

  Concentrated products for someone who wants triglyceride-form absorption without the ethyl-ester gap [1].

• Krill oilOff the table for anyone with a shellfish allergy — krill is a shellfish-derived product .

  Elemental content

  Omega-3s bound as phospholipids rather than as triglycerides or esters

  Absorption

  Genuinely unresolved, and NIH ODS flags it as unresolved rather than picking a side.
  
  Some head-to-head studies report higher plasma EPA/DHA from krill oil at equal or lower doses. Others find no meaningful difference [1].

  Best for

  Off the table for anyone with a shellfish allergy — krill is a shellfish-derived product [1].
  
  On triglycerides specifically, the sources conflict.
  
  One study cited by the National Lipid Association found about 28% lowering at 2–3 g/day krill oil, versus a non-significant 3.2% for fish oil [5]. Another cited study found the two comparable at matched EPA/DHA doses [5].
  
  That same source notes few studies have compared krill oil to fish oil head-to-head for triglycerides at all [5].

• Algal oilThe main vegetarian and vegan route to DHA, and the usual fallback for a fish or shellfish allergy .

  Elemental content

  Usually 100–300 mg DHA per serving, sometimes with some EPA, in triglyceride form

  Absorption

  A small controlled study found DHA from algal-oil capsules as bioavailable as DHA from eating cooked salmon [1].

  Best for

  The main vegetarian and vegan route to DHA, and the usual fallback for a fish or shellfish allergy [1].

• Cod liver oilNot a synonym for fish oil, and discouraged in pregnancy by some health authorities because excess vitamin A can harm a…

  Elemental content

  Pressed from cod liver rather than oily-fish flesh; also supplies vitamins A and D in amounts that vary by product

  Absorption

  Cod liver is less fatty than the flesh of salmon, mackerel, or herring.
  
  So a dose typically delivers less EPA and DHA than a concentrated fish-body oil [1].

  Best for

  Not a synonym for fish oil, and discouraged in pregnancy by some health authorities because excess vitamin A can harm a fetus [1].
  
  Its vitamins A and D are useful in adequate amounts and harmful in excess, which is the whole reason for that carve-out [12].

• Common mild effects

  Unpleasant taste, bad breath, heartburn, nausea, general gastrointestinal discomfort, diarrhea, headache, and odoriferous sweat [1][4].
  
  Splitting the daily dose across two meals is the usual first move for the gastrointestinal ones [9]. ^[1]

• Atrial fibrillation at 4 g/day

  The clearest cardiac signal comes from STRENGTH (2020), where 4 g/day of EPA+DHA produced a higher rate of atrial fibrillation than corn-oil placebo across 13,078 patients [1].
  
  This is a high-dose finding, not a statement about a single 1,000 mg capsule.
  
  It sits alongside the FDA's position that US supplement labels should not recommend more than 2 g/day of combined EPA+DHA [1]. ^[1]

• Fish and shellfish allergy

  Fish oil, cod liver oil, and krill oil are all out for people with the matching allergy, and krill specifically carries a shellfish allergen [1].
  
  Algal oil and flaxseed oil are the usual alternatives [1]. ^[1]

• Immune response at sustained high doses

  NIH ODS notes that 900 mg or more of EPA plus 600 mg or more of DHA daily, sustained over several weeks, may suppress the inflammatory immune response [1].
  
  Separately, the IOM flagged 2–15 g/day as a range where bleeding time may lengthen through reduced platelet aggregation [1]. ^[1]

• Warfarin and other anticoagulants

  Fish oil has mild antiplatelet activity at high doses, weaker than aspirin, and may lengthen clotting time or raise INR alongside warfarin [1].
  
  Most research at 3–6 g/day found no significant change in anticoagulant status, and FDA-approved labeling for prescription omega-3 products reports no clinically significant bleeding episodes [1].
  
  Those same labels still advise periodic INR monitoring. Drug databases classify the pairing as a moderate interaction [10]. ^[1]

• Aspirin, clopidogrel, other antiplatelet drugs

  Stacking omega-3s with other blood-thinning drugs or supplements is flagged as a moderate interaction risk for bruising and bleeding [10].
  
  The standard advice is caution and monitoring rather than avoidance [10]. ^[10]

• Cyclosporine, sirolimus, tacrolimus

  Fish oil may raise blood levels of these three immunosuppressants, and with them both the drug effects and the side effects [10].
  
  Anyone taking them should raise a fish oil supplement with the prescribing clinician before starting [10]. ^[10]

• Blood-pressure medication

  Omega-3s lower blood pressure modestly on their own, so pairing them with ACE inhibitors, beta-blockers, or diuretics can be additive [10].
  
  Drug databases class this as a minor but real interaction, with blood-pressure monitoring suggested [10]. ^[10]

• Orlistat

  Fish oil absorption may drop when it is taken close to the weight-loss drug orlistat [10].
  
  A gap of roughly 2 hours between the two is the suggested workaround [10]. ^[10]

• Hormonal contraceptives

  Some hormonal contraceptives may blunt the triglyceride-lowering effect of omega-3s [10].
  
  The documented effect runs in that direction — on the supplement, not on the contraceptive [10]. ^[10]

Only marine sources supply EPA and DHA directly. Plant foods supply ALA, and the body converts less than 15% of it onward, so they do not reliably substitute [1].

Plant (ALA), per USDA figures compiled by NIH ODS: flaxseed oil 7.26 g/tbsp, chia seeds 5.06 g/oz, English walnuts 2.57 g/oz, whole flaxseed 2.35 g/tbsp [1].

Canola oil (about 1.3 g/tbsp) and soybean oil (about 0.9 g/tbsp) are the more modest ALA sources [1].

Marine (EPA+DHA), per 3-ounce cooked serving [1]:

Farmed Atlantic salmon 1.24 g DHA + 0.59 g EPA; wild Atlantic salmon 1.22 g DHA + 0.35 g EPA [1].

Atlantic herring 0.94 g DHA + 0.77 g EPA; canned sardines in tomato sauce 0.74 g DHA + 0.45 g EPA [1].

Atlantic mackerel 0.59 g DHA + 0.43 g EPA [1]. Leaner fish like cod and tilapia, and shellfish, carry much smaller amounts [1].

Farmed fish generally carry more EPA/DHA than wild-caught, though that depends entirely on what they were fed. One analysis found EPA/DHA in farmed Scottish Atlantic salmon fell significantly between 2006 and 2015 as feed moved away from marine ingredients [1].

On mercury: FDA and EPA guidance asks pregnant and breastfeeding women to eat 8–12 oz per week of lower-mercury seafood — salmon, anchovies, sardines, Pacific oysters, trout [1].

That is framed as variety rather than avoidance. Systematic reviews cited by NIH ODS conclude the benefits of prenatal seafood at those intakes generally outweigh the mercury-related risk [1].

No time of day has been shown to matter. No significant difference in EPA/DHA absorption or effect has been demonstrated between morning and evening dosing [9].

What does matter is fat. A 2019 review found pairing an omega-3 concentrate with fat-containing food raised bioavailability; a 2015 review found absorption dropped with a low-fat meal [9].

The presumed mechanism is bile — dietary fat triggers the bile release needed to emulsify these lipids for absorption [9].

For belching, fishy aftertaste, or diarrhea, splitting the daily dose across two meals helps more than moving the hour [9]. Freezing the capsules or switching to an enteric-coated formulation is also suggested for the aftertaste [5].