A reference work, not a recommendation to use: this profile describes mechanism and evidence and does not replace medical advice. The claims come from marketing and forums and are tested here, not endorsed.

Claims checked

  • Protects heart and vessels from myocardial infarction and stroke

    No benefit

    Heart & blood vessels · healthy (primary prevention, people aged 50 and 55 years and older, respectively) · Human, randomised

    In VITAL (25,871 participants, 5.3 years), no reduction in major cardiovascular events; only the secondary endpoint myocardial infarction was less frequent [7]. Cochrane: little or no effect on mortality and cardiovascular events, at most slightly fewer coronary events with low certainty [6]. According to the design paper, VITAL used Omacor [17], that is, the form of the profile omega-3 acid ethyl esters; there, the less frequent myocardial infarction as a secondary endpoint is rated “Single unconfirmed finding.” For the promise assessed here, myocardial infarction and stroke together, it remains “No benefit”: the prespecified combined endpoint, stroke and cardiovascular death remained unchanged [7].

  • Lowers blood lipids (triglycerides; marker only)

    Only markers proven

    Energy & metabolism · mixed: adults with varying cardiovascular risk (primary and secondary prevention) · Human, randomised

    Marker only (K3; until October 25, 2026 “Proven benefit”). Cochrane meta-analysis: triglycerides lowered by about 15%, depending on the amount, high certainty; other blood lipids hardly changed [6]. Whether this alone is clinically useful is open [6][10].[10]

  • High-dose EPA lowers cardiovascular risk by 25%

    Single unconfirmed finding

    Heart & blood vessels · Patients: cardiovascular disease or diabetes with elevated triglycerides on a statin · Human, randomised

    For pure, high-dose EPA there is a single blinded endpoint study: REDUCE-IT, HR 0.75, funded by the manufacturer; the mineral oil in the comparator arm caused inflammatory and lipid values to rise in the placebo group [8][9]. The open study RESPECT-EPA with the same active substance showed the same direction but narrowly missed the primary endpoint (HR 0.79; 95% CI 0.62–1.00) and included a different population [18]. The older open study JELIS was positive (major coronary events relatively −19%) but included people with hypercholesterolemia without a triglyceride criterion, had no placebo group and does not name the chemical form in the abstract; it therefore does not confirm the promise for this population [19]. STRENGTH (HR 0.99) tested an EPA-DHA mixture as carboxylic acids against corn oil, that is, not pure EPA, and therefore does not refute the promise [10]. Until October 25, 2026 “Mixed results”; now the same rating as in the form profile icosapent ethyl.[8][9]

  • Keeps the brain fit and protects against mental decline

    No benefit

    Cognition & focus · healthy (cognitively healthy older adults) · Human, randomised

    Meta-analysis of 38 RCTs (49,757 participants): no effect on new cognitive impairment or dementia, MMSE difference 0.10 points [13]. Cochrane review in people over 60 without impairment: no benefit [14].

  • Lifts mood and helps against depression

    Mixed results

    Mood & stress · Patients: major depression · Human, randomised

    Cochrane (33 studies, 1848 participants): SMD −0.40, corresponding to about 2.5 points on the Hamilton scale and below the clinically relevant threshold; very low certainty, probably biased in favor of omega-3 [15]. For prevention in people without depression, somewhat more depression under omega-3 (HR 1.13) [16].

Mechanism of action

Evidence map: Omega-3 fatty acids (EPA and DHA)

Each line stands for a published finding; line style and color show where it comes from. The filter hides weaker evidence levels. Sources: see references.

EPA and DHA are taken up through the diet and incorporated into the phospholipids of cell membranes and lipoproteins. The brain cannot make DHA itself. In mice, the transporter MFSD2A in the endothelium of the blood-brain barrier is the most important route: it transports DHA not as a free fatty acid but bound as lysophosphatidylcholine; mice without MFSD2A had markedly less DHA in the brain, loss of nerve cells, learning deficits and pronounced anxiety [1]. Whether this implies a benefit of additional intake in well-supplied people is not something this animal work can say.

How well the fatty acids are absorbed depends on the chemical form and the meal. Ethyl esters, the form of many concentrates, were absorbed about three times better with a high-fat meal than with a low-fat one, up to about 60%; EPA from natural fish oil triglycerides, by contrast, was absorbed at 69% (low-fat) and 90% (high-fat), respectively [2]. In a two-week comparison with 72 volunteers, re-esterified triglycerides reached 124%, ethyl esters 73% and free fatty acids 91% of the bioavailability of natural fish oil [3]. A review ranks the forms as free fatty acids > phospholipids > re-esterified > natural triglycerides > ethyl esters, but stresses that differences after single doses often disappear with long-term use; one author holds shares in a laboratory for fatty acid testing [4]. For krill oil (phospholipids), a small crossover study showed a greater rise in the omega-3 index than for fish oil; two authors were employed by the krill oil manufacturer and designed the study, and only the krill oil capsules additionally contained astaxanthin [5].

The best-documented effect in humans is the reduction of triglycerides by about 15%, depending on the amount [6]. This hardly translates into hard endpoints: a Cochrane review with 86 randomized studies and 162,796 participants found little or no effect on all-cause mortality and cardiovascular events, at most a slight decrease in coronary events with low certainty [6]. In VITAL, a primary prevention study of 25,871 people aged 50 and 55 years and older, respectively, omega-3 capsules over 5.3 years reduced neither major cardiovascular events (HR 0.92; 95% CI 0.80–1.06) nor cancer; only the secondary endpoint myocardial infarction was less frequent (HR 0.72) [7]. High-dose pure EPA ethyl ester (icosapent ethyl) lowered the combined endpoint by 25% (HR 0.75) in REDUCE-IT in statin-treated at-risk patients with elevated triglycerides [8]. The manufacturer funded the study, and the comparator oil was mineral oil: in the placebo group, LDL cholesterol, CRP, interleukin-6 and interleukin-1β rose markedly, under EPA hardly at all [9]. The similarly large STRENGTH study with an EPA-DHA mixture versus corn oil was stopped early for futility (HR 0.99) [10].

The risks include a slightly increased risk of atrial fibrillation (HR 1.25 in seven large studies, stronger at higher amounts) [11]. Bleeding was not more frequent overall, but with high-dose pure EPA it was relatively 50% and absolutely 0.6 percentage points higher [12]. For the brain, two meta-analyses of randomized studies in cognitively healthy older people found no protection against mental decline or dementia [13][14]. For major depression, a Cochrane review found a small effect, probably clinically insignificant and probably overestimated [15]; in the VITAL depression study with 18,353 participants without current depression, depression even occurred slightly more often under omega-3 (HR 1.13) [16].

Forms and precursor: the large endpoint studies each used a specific form; the details are in the form profiles. According to the design paper, VITAL tested the medicinal product Omacor [17], whose form is covered by the profile omega-3 acid ethyl esters. REDUCE-IT used pure EPA ethyl ester (icosapent ethyl) [8]; the open Japanese study RESPECT-EPA with the same active substance narrowly missed its primary endpoint in stable coronary artery disease and a low EPA/AA ratio (HR 0.79; 95% CI 0.62–1.00), while coronary events as a secondary endpoint were less frequent [18]. The older open Japanese study JELIS, with highly purified EPA in 18,645 people with hypercholesterolemia on a statin, reduced major coronary events by 19% relative (2.8 vs. 3.5%); the control group received only the statin, without placebo, and the abstract does not name which chemical form was used [19]. STRENGTH used a carboxylic acid formulation of EPA and DHA, that is, not pure EPA [10]. The plant omega-3 fatty acid alpha-linolenic acid (ALA, separate profile) is the precursor of EPA and DHA: according to a statement by the scientific society ISSFAL, supplemental ALA raises EPA and docosapentaenoic acid in the blood, but hardly DHA; blood DHA rises reliably only with preformed DHA [20]. In the EU, the health claim “EPA and DHA contribute to the normal function of the heart” is authorized for EPA and DHA [21]; this is a legal decision, not an evidence level.

Targets

TargetTypeActionKey dataEvidence
MFSD2A (transporter in the endothelium of the blood-brain barrier)TransporterBindingtransports DHA as lysophosphatidylcholine, sodium-dependent; knockout: markedly less DHA in the brain (mouse, cell models) Animal study[1]
Serum triglyceridesOtherInhibitor≈ −15%, depending on the amount (meta-analysis of RCTs, high certainty) Human, randomised[6]
Phospholipids of the erythrocyte membrane (omega-3 index)OtherBindingIncorporation of EPA and DHA; rise differs by form (small RCT) Human, randomised[5]

Effect profile

Which signaling systems the compound affects according to current data. ↑ enhanced, ↓ dampened, ≈ modulated, ○ no effect; dots = evidence level.

  • Dopamineno data
  • Noradrenalineno data
  • Serotoninno data
  • Acetylcholineno data
  • Glutamate · AMPAno data
  • Glutamate · NMDAno data
  • GABAno data
  • Histamineno data
  • Orexinno data
  • Adenosineno data
  • Opioidsno data
  • Melatoninno data
  • Neurotrophinsno data
  • Blood flowno data
  • Nitric oxideno data
  • Energy metabolismmodulated · Blood triglycerides lowered by about 15%; body weight, other blood lipids and blood pressure hardly changed[6]
  • Insulin · glucoseno data
  • Inflammation · oxidativeunclear · In REDUCE-IT, inflammatory markers remained almost constant under EPA but rose under the mineral oil comparator[9]
  • Stress axisno data
  • Testosterone axisno data
  • Endocannabinoidsno data
  • Autophagy · senescenceno data
  • Immune systemno data
  • Lipid metabolismno data
  • Coagulation · fibrinolysisno data
  • Methylationno data

Routes of administration and bioavailability

How much of a compound reaches the blood or target tissue depends on the route into the body and on the dosage form. All routes of administration explained

  • Oral (swallowed) · natural fish oil (triglycerides)

    EPA ≈ 69% (low-fat meal) and ≈ 90% (high-fat meal), respectively

    Absorption of EPA depended on the fat content of the meal, that of DHA did not; men, comparison with previously reported values [2].

    Human, non-randomised

  • Oral (swallowed) · Ethyl esters (concentrate)

    ≈ 60% with a high-fat meal, about one third of that with a low-fat meal; 73% relative to fish oil

    Absorption strongly dependent on co-ingested fat [2]; in a two-week comparison, poorer than natural fish oil [3]. Pure EPA ethyl ester (icosapent ethyl) also comes in this form [8].

    Human, randomised

  • Oral (swallowed) · re-esterified triglycerides and free fatty acids, respectively

    124% and 91%, respectively, relative to natural fish oil

    Two weeks, 72 volunteers; concentrated products double-blind against placebo oil, fish oil and cod liver oil arms single-blind [3]. Differences after single doses often disappear with long-term use [4].

    Human, randomised

  • Oral (swallowed) · Krill oil (phospholipids)

    Omega-3 index raised more than with fish oil (24 healthy people, crossover)

    Study designed by employees of the krill oil manufacturer; krill oil capsules additionally contained astaxanthin [5]. Clinical benefit not studied; a review sees mostly small differences with long-term use [4].

    Human, randomised

Human studies

  • VITAL (primary prevention)

    RCT, double-blind, placebo-controlled, 2×2 factorial · healthy (men aged 50 and older, women aged 55 and older, US) · n = 25871 · median 5.3 years

    Measured: major cardiovascular events, invasive cancer

    Result: No effect (HR 0.92 and 1.03, respectively); myocardial infarction as a secondary endpoint HR 0.72; no increase in bleeding.[7]

    Human, randomised

  • Cochrane review cardiovascular

    systematic review and meta-analysis of RCTs (≥ 12 months) · mixed: adults with varying cardiovascular risk (primary and secondary prevention) · n = 162796 · 12–88 months

    Measured: Mortality, cardiovascular events, blood lipids

    Result: All-cause mortality RR 0.97, cardiovascular events RR 0.96 (both high certainty); triglycerides ≈ −15%.[6]

    Human, randomised

  • REDUCE-IT (icosapent ethyl)

    RCT, double-blind, mineral oil as placebo · Patients: cardiovascular disease or diabetes with risk factors, elevated triglycerides on a statin · n = 8179 · median 4.9 years

    Measured: combined cardiovascular endpoint

    Result: HR 0.75; more hospital admissions for atrial fibrillation (3.1% vs. 2.1%); funded by the manufacturer.[8]

    Human, randomised

  • STRENGTH (EPA and DHA)

    RCT, double-blind, corn oil as comparator · Patients: high cardiovascular risk, elevated triglycerides, low HDL · n = 13078 · stopped early

    Measured: combined cardiovascular endpoint

    Result: No difference (12.0% vs. 12.2%; HR 0.99); more gastrointestinal complaints (24.7% vs. 14.7%).[10]

    Human, randomised

  • RESPECT-EPA (icosapent ethyl, open)

    RCT, open, blinded endpoint assessment · Patients: stable coronary artery disease, low EPA/AA ratio, statin (Japan) · n = 2506 · median 5 years

    Measured: combined cardiovascular endpoint

    Result: 9.1 vs. 12.6% (HR 0.79; p = 0.055); coronary events HR 0.73; new atrial fibrillation 3.1 vs. 1.6%.[18]

    Human, randomised

  • Meta-analysis of atrial fibrillation

    meta-analysis of 7 RCTs on cardiovascular endpoints · mixed: healthy and patients (cardiovascular endpoint studies) · n = 81210 · on average 4.9 years

    Measured: Atrial fibrillation

    Result: HR 1.25 (95% CI 1.07–1.46); stronger at higher amounts.[11]

    Human, randomised

  • Meta-analysis of cognition

    systematic review and meta-analysis of 38 RCTs (≥ 24 weeks) · healthy (mostly older adults) · n = 49757 · ≥ 24 weeks

    Measured: new cognitive disorder, MMSE

    Result: No effect on new disorder (RR 0.98) or impairment (RR 0.99); MMSE +0.10 points.[13]

    Human, randomised

  • Cochrane review depression

    systematic review of RCTs · Patients: major depression · n = 1848

    Measured: depressive symptoms

    Result: SMD −0.40, probably clinically insignificant, very low certainty; remission and response unchanged.[15]

    Human, randomised

  • VITAL-DEP (depression prevention)

    RCT, double-blind, placebo-controlled · healthy (aged 50 and older, without current depression) · n = 18353 · median 5.3 years

    Measured: new or recurrent depression, PHQ-8

    Result: Somewhat more depression under omega-3 (HR 1.13); mood scores unchanged.[16]

    Human, randomised

  • Comparison of fish oil forms

    controlled study, partly double-blind against placebo oil · healthy · n = 72 · 2 weeks

    Measured: EPA and DHA in serum lipids

    Result: Re-esterified triglycerides 124%, free fatty acids 91%, ethyl esters 73% of natural fish oil.[3]

    Human, randomised

Risks and warnings

  • Atrial fibrillation

    Meta-analysis of seven large RCTs: HR 1.25, at higher amounts 1.49 compared with 1.12 at lower ones; per additional gram HR 1.11 [11]. In REDUCE-IT 3.1% vs. 2.1% hospital admissions for atrial fibrillation [8].

    Human, randomised

  • Bleeding

    Not more frequent overall (RR 1.09; eleven RCTs, 120,643 participants); with high-dose pure EPA relatively +50%, absolutely +0.6 percentage points [12]. No increase in VITAL [7].

    Human, randomised

  • Gastrointestinal complaints

    In STRENGTH 24.7% versus 14.7% under corn oil [10]; in the Cochrane review on cognition, mild gastrointestinal complaints as the most common side effect [14].

    Human, randomised

  • Depression in a prevention study

    In VITAL-DEP, depression or relevant depressive symptoms occurred somewhat more often under omega-3 (HR 1.13; 95% CI 1.01–1.26); mood scores did not differ [16]. Single finding.

    Human, randomised

Interactions

  • Platelet inhibitors: In the bleeding meta-analysis, the bleeding risk did not depend on concomitant platelet inhibition, but did depend on the amount of EPA [12].

Fact check: common claims

  • partly supported

    “Fish oil protects against myocardial infarction and stroke”

    In healthy people, no effect on the main endpoint and none on stroke; myocardial infarction less frequent only as a secondary endpoint [7]. Cochrane: at most slightly fewer coronary events with low certainty [6].

  • refuted

    “Omega-3 capsules protect against mental decline in old age”

    Meta-analysis of 38 RCTs with almost 50,000 participants and Cochrane review without benefit in cognitively healthy people [13][14].

  • partly supported

    “Pure EPA lowers the heart risk by a quarter”

    So in REDUCE-IT in at-risk patients [8], but manufacturer-funded and with a mineral oil comparator under which inflammatory and lipid values rose [9]; the similarly large STRENGTH study with an EPA-DHA mixture in a different form found no effect [10], and the open study RESPECT-EPA with pure EPA narrowly missed its primary endpoint [18].

  • partly supported

    “Krill oil works better than fish oil because it is absorbed better”

    Greater rise in the omega-3 index in a small study co-designed by the manufacturer [5]; a clinical benefit has not been shown, and with long-term use differences between forms are mostly small [4].

  • refuted

    “Omega-3 is completely free of side effects”

    Slightly increased risk of atrial fibrillation in randomized studies [11], more gastrointestinal complaints [10] and, with high-dose EPA, somewhat more bleeding [12].

Pharmacokinetics

Absorption
Depending on form and meal: ethyl esters with a high-fat meal ≈ 60%, otherwise markedly less; EPA from fish oil triglycerides 69–90% [2][3].
Half-life
Not verified.
Metabolism
Incorporation into phospholipids of membranes and lipoproteins; rise in erythrocytes (omega-3 index) over weeks [5].
Entry into the brain
In mice, DHA is transported into the brain as lysophosphatidylcholine via MFSD2A [1]; not examined in humans here.

Legal status

Germany
Not verified.
EU
For EPA and DHA, the health claim on heart function is authorized; it applies to the fatty acids, not to a specific form [21]. The medicinal product and food status of the individual forms are given in the form profiles and were not specifically checked for this overview profile.
USA
Not verified.

Authorised EU health claims

EU claim authorised An authorised health claim is a legal statement about the nutrient, not about this form, and not a level of evidence. The evidence for this form is reported separately under the main claim and in the human studies.

  • “contribute to the normal function of the heart”

    Nutrient
    Eicosapentaenoic acid and docosahexaenoic acid (EPA/DHA)
    Legal basis
    Regulation (EU) No 432/2012[21]
    Reading
    legally permitted; in healthy people, no protection against myocardial infarction and stroke overall has been shown (see main promise)

Related compounds

Alpha-Linolensäuresame class (German only)

Open questions

  • Is the benefit in REDUCE-IT real, or did the mineral oil in the placebo group do harm?
  • Do people with a low baseline level (low omega-3 index) benefit more than well-supplied ones?
  • How strongly does the risk of atrial fibrillation rise at the amounts common in supplements?
  • Does additionally supplied DHA reach more brain tissue at all in well-supplied adults?

References

  1. Nguyen LN, Ma D, Shui G, Wong P, Cazenave-Gassiot A, Zhang X, et al. Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. Nature. 2014;509(7501):503–6. doi:10.1038/nature13241 · PubMed
  2. Lawson LD, Hughes BG. Absorption of eicosapentaenoic acid and docosahexaenoic acid from fish oil triacylglycerols or fish oil ethyl esters co-ingested with a high-fat meal. Biochem Biophys Res Commun. 1988;156(2):960–3. doi:10.1016/s0006-291x(88)80937-9 · PubMed
  3. Dyerberg J, Madsen P, Møller JM, Aardestrup I, Schmidt EB. Bioavailability of marine n-3 fatty acid formulations. Prostaglandins Leukot Essent Fatty Acids. 2010;83(3):137–41. doi:10.1016/j.plefa.2010.06.007 · PubMed
  4. Alijani S, Hahn A, Harris WS, Schuchardt JP. Bioavailability of EPA and DHA in humans – a comprehensive review. Prog Lipid Res. 2025;97:101318. doi:10.1016/j.plipres.2024.101318 · PubMed
  5. Ramprasath VR, Eyal I, Zchut S, Jones PJ. Enhanced increase of omega-3 index in healthy individuals with response to 4-week n-3 fatty acid supplementation from krill oil versus fish oil. Lipids Health Dis. 2013;12:178. doi:10.1186/1476-511X-12-178 · PubMed
  6. Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020;3(3):CD003177. doi:10.1002/14651858.CD003177.pub5 · PubMed
  7. Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, et al. Marine n-3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med. 2019;380(1):23–32. doi:10.1056/NEJMoa1811403 · PubMed
  8. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22. doi:10.1056/NEJMoa1812792 · PubMed
  9. Ridker PM, Rifai N, MacFadyen J, Glynn RJ, Jiao L, Steg PG, et al. Effects of randomized treatment with icosapent ethyl and a mineral oil comparator on interleukin-1β, interleukin-6, C-reactive protein, oxidized low-density lipoprotein cholesterol, homocysteine, lipoprotein(a), and lipoprotein-associated phospholipase A2: a REDUCE-IT biomarker substudy. Circulation. 2022;146(5):372–9. doi:10.1161/CIRCULATIONAHA.122.059410 · PubMed
  10. Nicholls SJ, Lincoff AM, Garcia M, Bash D, Ballantyne CM, Barter PJ, et al. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: the STRENGTH randomized clinical trial. JAMA. 2020;324(22):2268–80. doi:10.1001/jama.2020.22258 · PubMed
  11. Gencer B, Djousse L, Al-Ramady OT, Cook NR, Manson JE, Albert CM. Effect of long-term marine ω-3 fatty acids supplementation on the risk of atrial fibrillation in randomized controlled trials of cardiovascular outcomes: a systematic review and meta-analysis. Circulation. 2021;144(25):1981–90. doi:10.1161/CIRCULATIONAHA.121.055654 · PubMed
  12. Javaid M, Kadhim K, Bawamia B, Cartlidge T, Farag M, Alkhalil M. Bleeding risk in patients receiving omega-3 polyunsaturated fatty acids: a systematic review and meta-analysis of randomized clinical trials. J Am Heart Assoc. 2024;13(10):e032390. doi:10.1161/JAHA.123.032390 · PubMed
  13. Brainard JS, Jimoh OF, Deane KHO, Biswas P, Donaldson D, Maas K, et al. Omega-3, omega-6, and polyunsaturated fat for cognition: systematic review and meta-analysis of randomized trials. J Am Med Dir Assoc. 2020;21(10):1439–50.e21. doi:10.1016/j.jamda.2020.02.022 · PubMed
  14. Sydenham E, Dangour AD, Lim WS. Omega 3 fatty acid for the prevention of cognitive decline and dementia. Cochrane Database Syst Rev. 2012;(6):CD005379. doi:10.1002/14651858.CD005379.pub3 · PubMed
  15. Appleton KM, Voyias PD, Sallis HM, Dawson S, Ness AR, Churchill R, et al. Omega-3 fatty acids for depression in adults. Cochrane Database Syst Rev. 2021;11(11):CD004692. doi:10.1002/14651858.CD004692.pub5 · PubMed
  16. Okereke OI, Vyas CM, Mischoulon D, Chang G, Cook NR, Weinberg A, et al. Effect of long-term supplementation with marine omega-3 fatty acids vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores: a randomized clinical trial. JAMA. 2021;326(23):2385–94. doi:10.1001/jama.2021.21187 · PubMed
  17. Manson JE, Bassuk SS, Lee IM, Cook NR, Albert MA, Gordon D, et al. The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials. 2012;33(1):159–71. doi:10.1016/j.cct.2011.09.009 · PubMed
  18. Miyauchi K, Iwata H, Nishizaki Y, Inoue T, Hirayama A, Kimura K, et al. Randomized trial for evaluation in secondary prevention efficacy of combination therapy–statin and eicosapentaenoic acid (RESPECT-EPA). Circulation. 2024;150(6):425–34. doi:10.1161/CIRCULATIONAHA.123.065520 · PubMed
  19. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090–8. doi:10.1016/S0140-6736(07)60527-3 · PubMed
  20. Brenna JT, Salem N Jr, Sinclair AJ, Cunnane SC; International Society for the Study of Fatty Acids and Lipids, ISSFAL. alpha-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids. 2009;80(2–3):85–91. doi:10.1016/j.plefa.2009.01.004 · PubMed
  21. Verordnung (EU) Nr. 432/2012 der Kommission vom 16. Mai 2012 zur Festlegung einer Liste zulässiger anderer gesundheitsbezogener Angaben über Lebensmittel als Angaben über die Reduzierung eines Krankheitsrisikos sowie die Entwicklung und die Gesundheit von Kindern. ABl. L 136 vom 25.5.2012, S. 1 (CELEX 32012R0432).
How this profile was checked

Last reviewed: 2026-10-25. All sources with a DOI or PMID were resolved automatically via Crossref or doi.org and PubMed.

Translated from the German profile (version of 2026-10-25); translation checked on 2026-10-26.

Checked

  • All abstracts read via PubMed (efetch); DOIs and PMIDs reconciled with tools/pruefe_profile.py via Crossref and PubMed.
  • Key figures checked against the abstracts: MFSD2A transports LPC-DHA, knockout with DHA deficiency, neuron loss, learning and anxiety phenotype [1]; EPA 69 → 90%, ethyl ester threefold to ≈ 60% [2]; n = 72, 124%/73%/91% [3]; order NEFA > PL > rTAG > TAG > EE, conflict of interest OmegaQuant [4]; n = 24, omega-3 index krill > fish [5]; 86 RCTs, 162,796, RR 0.97/0.96, triglycerides ≈ −15% [6]; n = 25,871, HR 0.92, myocardial infarction 0.72 [7]; n = 8179, HR 0.75, atrial fibrillation 3.1 vs. 2.1%, funding Amarin [8]; biomarker rises under mineral oil [9]; n = 13,078, HR 0.99, GI 24.7 vs. 14.7% [10]; HR 1.25/1.49/1.12/1.11 [11]; RR 1.09, +50% relative, +0.6% absolute with EPA [12]; 38 RCTs, 49,757, RR 0.98/0.99, MMSE 0.10 [13]; 3 studies, no benefit [14]; SMD −0.40, ≈ 2.5 HDRS points [15]; n = 18,353, HR 1.13 [16].
  • In the full text (PMC4235028) [5]: two authors employed at Enzymotec designed the study and protocol; krill oil supplied by the manufacturer; only the krill oil capsules contained astaxanthin.
  • PubChem: EPA is CID 446284 (all-cis), DHA is CID 445580.
  • ClinicalTrials.gov: 1869 entries for “omega-3 fatty acids” (October 23, 2026).
  • October 25, 2026, q038 (E-6): overview profile of the family omega-3-fettsaeuren-formen; “Krill oil” and “icosapent ethyl (pure EPA ethyl ester)” (separate form profiles) removed from synonyme. “Fish oil” and “algal oil” remain as terms of origin for all forms (cross-check October 25, 2026: there is no form profile “algal oil”; according to the guideline, algal oil is an origin, not a form, and until then was no longer listed as a synonym in any profile).
  • October 25, 2026, q080: heart protection reconciled with the form profile omega-3 acid ethyl esters. Abstract VITAL [7]: primary endpoint HR 0.92 (0.80–1.06), myocardial infarction 0.72 (0.59–0.90), stroke 1.04 (0.83–1.31), cardiovascular death 0.96 (0.76–1.21); design paper [17]: “Omacor fish oil.” Main promise (myocardial infarction and stroke together) remains “No benefit”; the form profile rates only myocardial infarction (“Single unconfirmed finding”); both rationales now refer to each other. Abstracts REDUCE-IT [8] (HR 0.75; 0.68–0.83; Amarin), STRENGTH [10] (carboxylic acid formulation of EPA and DHA, HR 0.99), RESPECT-EPA [18] (open, HR 0.79; 0.62–1.00; p = 0.055) and ASCEND (PMID 30146932, form not named, not cited here) read. Promise “High-dose EPA …” changed from “Mixed results” to “Single unconfirmed finding” because STRENGTH did not test pure EPA; same reading as in the profile icosapent ethyl.
  • October 25, 2026, q009 (K3): triglyceride promise labeled as a pure marker promise, result “Proven benefit” → “Only markers proven” (reduction according to Cochrane [6] directional and confirmed).
  • October 25, 2026, q082: health claim “EPA and DHA contribute to the normal function of the heart” read in the base text of Regulation (EU) No 432/2012 (CELEX 32012R0432, DE, via Cellar); conditions with amounts not included. Entered in health_claims and status.eu [21].
  • October 25, 2026, q106: “related” to alpha-linolensaeure remains “same class” (omega-3 fatty acids); conversion ALA → EPA in the text supported by the abstract of the ISSFAL statement [20].
  • Cross-check October 25, 2026: JELIS added (abstract PMID 17398308 read via PubMed efetch: open, blinded endpoint assessment, 18,645 with total cholesterol ≥ 6.5 mmol/L, statin with or without EPA, 2.8 vs. 3.5%, relative −19%, p = 0.011; same reference as in the profile icosapent-ethyl, there no. 5); new reference [19], Brenna and Regulation (EU) No 432/2012 now [20] and [21]. Result “Single unconfirmed finding” remains because JELIS did not select participants by elevated triglycerides and had no placebo group. q008: population of the triglyceride promise and of the studies Cochrane [6] and atrial fibrillation [11] changed to “mixed: …” (Cochrane abstract: “adults at varying cardiovascular risk,” primary and secondary prevention; Gencer abstract: RCTs on cardiovascular endpoints, content otherwise unchanged).
  • October 25, 2026, q012: ratings are based, unless a full text is named above, only on the abstracts (abstract only checked); full text only for [5] (PMC4235028).

Not verified

  • Legal status (food supplement, medicinal product) not specifically checked in the overview profile, see form profiles; health claim checked only in the base text of Regulation (EU) No 432/2012, not in the consolidated version; the EFSA pages were not retrievable.
  • Half-life of EPA and DHA in plasma or erythrocytes not checked against a primary source.
  • Whether the absorption values for low-fat meals in [2] come from the same group of people (according to the abstract “previously reported”).
  • Randomization in [3] (the abstract says only “double-blinded design” and “single-blinded arms,” respectively).
  • Studies on cognition in young healthy people and on algal oil were not researched separately.
  • Chemical form of the JELIS product (abstract names only “EPA”; full text not checked).

No dosages, no sources of supply. This information does not replace medical advice.

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