Fish and omega-3 fats

What it is

Oily fish supply two long omega-3 fats, EPA and DHA; some plant oils supply a shorter one, α-linolenic acid (ALA) ¹².

Per 100 g, raw farmed Atlantic salmon contains 0.862 g eicosapentaenoic acid (EPA, 20:5 n-3) and 1.1 g docosahexaenoic acid (DHA, 22:6 n-3), and cold-pressed linseed oil 53.4 g ALA (18:3 n-3) ¹. Fish are the main dietary source of methylmercury; predatory species contain the most mercury ³.

In the body

The body converts only small amounts of ALA to EPA and DHA ⁴.

Humans lack Δ12- and Δ15-desaturases, so ALA is essential ⁴. FADS2 catalyses the first, rate-limiting Δ6-desaturation; ELOVL5 and FADS1 complete EPA, and ELOVL2, FADS2 and one peroxisomal β-oxidation cycle convert EPA to DHA ⁵.

α-Linolenic acid to docosahexaenoic acidEndoplasmic reticulum membrane, then peroxisome

α-Linolenic acid (18:3 n-3)
Long-chain-fatty-acid–CoA ligases (ACSL1, ACSL3 to ACSL6)ATP, CoAReleases AMP and diphosphate
α-Linolenoyl-CoA
Acyl-CoA 6-desaturase (FADS2)O2, 2 reduced cytochrome b5First, rate-limiting desaturation; shared with linoleoyl-CoA (n-6)
Stearidonoyl-CoA (18:4 n-3)
several stepsMalonyl-CoA, 2 NADPHElongation cycle: ELOVL5, HSD17B12, HACD1–4, TECR; releases CO2
Eicosatetraenoyl-CoA (20:4 n-3)
Acyl-CoA (8-3)-desaturase, Δ5-desaturase (FADS1)O2, 2 reduced cytochrome b5
Eicosapentaenoyl-CoA (EPA, 20:5 n-3)
several stepsMalonyl-CoA, 2 NADPHElongation cycle; ELOVL2 or ELOVL5 catalyses the condensation
Docosapentaenoyl-CoA (DPA, 22:5 n-3)
several stepsMalonyl-CoA, 2 NADPHElongation cycle; ELOVL2 catalyses the condensation
Tetracosapentaenoyl-CoA (24:5 n-3)
Acyl-CoA 6-desaturase (FADS2)O2, 2 reduced cytochrome b5Second Δ6-desaturation; human activity inferred by similarity
Tetracosahexaenoyl-CoA (24:6 n-3)
several stepsFAD, O2, H2O, NAD+, CoAOne peroxisomal β-oxidation cycle: ACOX1, HSD17B4, ACAA1; releases acetyl-CoA
Docosahexaenoyl-CoA (DHA, 22:6 n-3)

Estimated conversion is 8–12% to EPA and possibly under 1% to DHA; dietary linoleic acid, converted by the same enzymes, lowers it ⁴. Homozygotes for the derived FADS haplotype D had 24% more plasma DHA than those for haplotype A ⁶.

Methylmercury crosses the placenta and blood–brain barrier; EFSA derived its tolerable weekly intake, 1.3 µg/kg body weight, from prenatal neurodevelopment, and high fish consumers may exceed it up to about sixfold ³.

What studies show

In independently funded research, fish-oil capsules did not reduce heart attacks and strokes taken together ⁷⁸.

VITAL gave 25,871 US adults without cardiovascular disease 1 g fish oil daily (460 mg EPA, 380 mg DHA) or placebo; over a median 5.3 years, major cardiovascular events occurred in 3.0% against 3.2% (hazard ratio 0.92, 95% CI 0.80 to 1.06) ⁷.

In a meta-analysis of 10 trials in 77,917 high-risk people (mean 4.4 years), the rate ratio for major vascular events was 0.97 (0.93 to 1.01) ⁸.

Industry-funded results

ASCEND, whose capsule suppliers funded packaging and commented on its design and manuscript, gave 15,480 UK adults with diabetes the same dose or olive oil ⁹. Over a mean 7.4 years, serious vascular events occurred in 8.9% against 9.2% (rate ratio 0.97, 0.87 to 1.08) ⁹.

REDUCE-IT, sponsored and analysed by Amarin, gave 8179 statin-treated patients with raised triglycerides 4 g daily of icosapent ethyl (EPA ethyl ester) or a mineral-oil placebo ¹⁰. Over a median 4.9 years, the primary composite occurred in 17.2% against 22.0% (hazard ratio 0.75, 0.68 to 0.83), a difference of 4.8 percentage points (number needed to treat 21), and hospitalisation for atrial fibrillation or flutter in 3.1% against 2.1% ¹⁰.

STRENGTH, funded by AstraZeneca, compared 4 g daily of EPA and DHA carboxylic acids with corn oil in 13,078 statin-treated patients; it was stopped for futility at a median 42.0 months ¹¹. Primary events occurred in 12.0% against 12.2% (hazard ratio 0.99, 0.90 to 1.09), and new atrial fibrillation in 2.2% against 1.3% (number needed to harm 114) ¹¹.

References

Textbook or database
Fukagawa NK, McKillop K, Pehrsson PR, Moshfegh A, Harnly J, Finley J. USDA's FoodData Central: what is it and why is it needed today? American Journal of Clinical Nutrition, 2022.
doi:10.1093/ajcn/nqab397 PubMed 34893796
Funding and finding
Funding
All authors are employed by the USDA Agricultural Research Service and have not received external support in the preparation of this manuscript.
Finding
FoodData Central records read 2026-10-21, per 100 g. 'Fish, salmon, Atlantic, farmed, raw' (FDC 175167, NDB 15236): energy 208 kcal; total fat 13.4 g; 20:5 n-3 (EPA) 0.862 g, 22:5 n-3 (DPA) 0.393 g, 22:6 n-3 (DHA) 1.1 g and 18:3 n-3 (ALA) 0.148 g, each analytical with 4 data points. 'Oil, flaxseed, cold pressed' (FDC 167702, https://fdc.nal.usda.gov/portal-data/external/167702): total fat 100 g; 18:3 n-3 (ALA) 53.4 g; 18:2 n-6 14.2 g; EPA, DPA and DHA 0.0 g.
Regulator
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on health benefits of seafood (fish and shellfish) consumption in relation to health risks associated with exposure to methylmercury EFSA Journal, 2014.
doi:10.2903/j.efsa.2014.3761
Funding and finding
Funding
European Food Safety Authority, on request from the European Commission (Question No EFSA-Q-2013-00167).
Finding
Seafood is a source of protein, iodine, selenium, calcium and vitamins A and D, and provides n-3 long-chain polyunsaturated fatty acids. Consumption of about 1-2 servings of seafood per week and up to 3-4 servings per week during pregnancy has been associated with better functional outcomes of neurodevelopment in children compared to no seafood; such amounts have also been associated with a lower risk of coronary heart disease mortality in adults. These associations refer to seafood per se, including adverse effects of contaminants such as methylmercury; no additional benefit on neurodevelopment and no benefit on coronary mortality might be expected at higher intakes.
Regulator
EFSA Panel on Contaminants in the Food Chain (CONTAM). Scientific Opinion on the risk for public health related to the presence of mercury and methylmercury in food EFSA Journal, 2012.
doi:10.2903/j.efsa.2012.2985
Funding and finding
Funding
European Food Safety Authority, on request from the European Commission (Question No EFSA-Q-2011-00923).
Finding
Methylmercury is by far the most common form of organic mercury in the food chain; mercury content varied widely among fish species and was highest in predatory fish; tuna, swordfish, cod, whiting and pike were major contributors to adult exposure. Methylmercury is much more extensively and rapidly absorbed than mercuric and mercurous mercury, more than 90% of blood methylmercury is in erythrocytes, and it crosses the placenta and the blood-brain barrier; absorbed methylmercury is excreted mainly in faeces as mercuric mercury. On the basis of prenatal exposure and neurodevelopmental outcomes, the Panel established a tolerable weekly intake for methylmercury of 1.3 µg/kg body weight, expressed as mercury, against the JECFA provisional tolerable weekly intake of 1.6 µg/kg. The 95th percentile dietary exposure is close to or above the TWI for all age groups; high fish consumers, which might include pregnant women, may exceed it by up to approximately six-fold; unborn children are the most vulnerable group. The opinion does not assess the nutritional benefits of fish.
Regulator
EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA). Scientific Opinion on Dietary Reference Values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol EFSA Journal, 2010.
doi:10.2903/j.efsa.2010.1461
Funding and finding
Funding
European Food Safety Authority, on request from the European Commission (Question No EFSA-Q-2008-466).
Finding
Humans lack delta-12 and delta-15 desaturases, so linoleic acid and alpha-linolenic acid are essential; n-6 and n-3 fatty acids are desaturated and elongated by the same enzymes. Adequate intake 4% of energy for linoleic acid and 0.5% for alpha-linolenic acid. Less than 1% of deuterated linoleic acid was converted to arachidonic acid; alpha-linolenic acid conversion about 8 to 12% to EPA and less than 1% to DHA; conversion of ALA decreases as dietary linoleic acid increases; amounts of n-3 LCPUFA formed depend on ALA intake, not on the n-3/n-6 ratio. Linoleic acid has a negative, dose-dependent relationship with LDL cholesterol. No specific values set for the n-3/n-6 ratio because data on clinical and biochemical endpoints in humans are insufficient to recommend a ratio independent of absolute intakes. No consistent evidence that n-6 PUFA intake has detrimental effects; no upper level set.
Textbook or database
UniProt Consortium. UniProt: the Universal Protein Knowledgebase in 2025 Nucleic Acids Research, 2025.
doi:10.1093/nar/gkae1010 PubMed 39552041
Funding and finding
Funding
National Human Genome Research Institute [HG002273]; NIH Office of the Director [U24HG007822]; NIAID; NIA; NIGMS [R35GM141873]; NIDDK; NEI; NCI; NHLBI; BBSRC [BB/T015608/1]; National Science Foundation Directorate for Biological Sciences [BB/X002179/1]; Open Targets; Horizon 2020 [825575]; Swiss State Secretariat for Education, Research and Innovation; EMBL Australia.
Finding
Reviewed UniProtKB entries, release 2026_03, read through rest.uniprot.org. FADS2 (O95864), acyl-CoA 6-desaturase, endoplasmic reticulum membrane: introduces a cis double bond at carbon 6 and catalyses the first and rate-limiting step of highly unsaturated fatty acid synthesis, the desaturation of linoleoyl-CoA (18:2n-6) and alpha-linolenoyl-CoA (18:3n-3) to gamma-linolenoyl-CoA and stearidonoyl-CoA (18:4n-3), with O2 and 2 Fe(II)-cytochrome b5; in the n-3 series it also desaturates tetracosapentaenoyl-CoA (24:5n-3) to tetracosahexaenoyl-CoA (24:6n-3), which is converted to DHA (by similarity); it carries an N-terminal cytochrome b5 domain and three histidine boxes. FADS1 (O60427), acyl-CoA (8-3)-desaturase: front-end desaturase that introduces a cis double bond at carbon 5 and desaturates dihomo-gamma-linolenoyl-CoA (20:3n-6) and eicosatetraenoyl-CoA (20:4n-3) to arachidonoyl-CoA and eicosapentaenoyl-CoA (20:5n-3). ELOVL5 (Q9NYP7): condensing enzyme of the elongation cycle, its first and rate-limiting reaction, acting on polyunsaturated acyl-CoAs including stearidonoyl-CoA and eicosapentaenoyl-CoA with malonyl-CoA and releasing CO2 and CoA. ELOVL2 (Q9NXB9): condensing enzyme for C20 and C22 polyunsaturated acyl-CoAs, including eicosapentaenoyl-CoA and docosapentaenoyl-CoA (22:5n-3), the latter to 3-oxotetracosapentaenoyl-CoA. HSD17B12 (Q53GQ0, NADPH-dependent 3-ketoacyl-CoA reductase), HACD1 to HACD4 (B0YJ81, Q6Y1H2, Q9P035, Q5VWC8; 3-hydroxyacyl-CoA dehydratases) and TECR (Q9NZ01, NADPH-dependent trans-2,3-enoyl-CoA reductase) catalyse the second, third and fourth reactions of the endoplasmic reticulum elongation cycle. ACOX1 (Q15067), peroxisomal acyl-CoA oxidase 1, FAD: initial and rate-limiting step of peroxisomal beta-oxidation, donating electrons directly to O2 to form H2O2; acts on tetracosahexaenoyl-CoA; possibly regulates systemic DHA through peroxisomal beta-oxidation of 24:6n-3 to DHA. HSD17B4 (P51659), peroxisomal multifunctional enzyme type 2: hydration of 2-enoyl-CoA and NAD+-dependent dehydrogenation of (3R)-3-hydroxyacyl-CoA, including the C24 hexaenoyl intermediates. ACAA1 (P09110), peroxisomal 3-ketoacyl-CoA thiolase: 3-oxo-tetracosahexaenoyl-CoA + CoA = docosahexaenoyl-CoA + acetyl-CoA. ACSL1 (P33121): a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-CoA + AMP + diphosphate; ACSL3 (O95573), ACSL4 (O60488), ACSL5 (Q9ULC5) and ACSL6 (Q9UKU0) catalyse the same reaction, and ACSL3 activates (9Z,12Z,15Z)-octadecatrienoate (alpha-linolenate) to its CoA ester (by similarity).
Independent research
Ameur A, Enroth S, Johansson A, Zaboli G, Igl W, Johansson AC, et al. Genetic adaptation of fatty-acid metabolism: a human-specific haplotype increasing the biosynthesis of long-chain omega-3 and omega-6 fatty acids American Journal of Human Genetics, 2012.
doi:10.1016/j.ajhg.2012.03.014 PubMed 22503634
Funding and finding
Participants
5,652
Funding
The study was supported by grants from the Swedish Research Council. Sequencing and genotyping were performed by the Uppsala Genome Center, funded by the Knut and Alice Wallenberg foundation, the Swedish Research Council and Science for Life Laboratory Uppsala.
Finding
Two common FADS haplotypes, A and D, defined by 28 SNPs across 38.9 kb. Haplotype D homozygotes had 43% higher arachidonic acid and 24% higher docosahexaenoic acid than haplotype A homozygotes, and higher hepatic FADS1 expression. Haplotype A frequency: 1% of chromosomes in African HGDP populations, 25% to 50% in Europe, West, South and East Asia and Oceania, 97% in 126 Native Americans. Haplotype D appeared on the lineage leading to modern humans and shows evidence of positive selection.
Independent research
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 New England Journal of Medicine, 2019.
doi:10.1056/NEJMoa1811403 PubMed 30415637
Funding and finding
Registration
NCT01169259
Participants
25,871
Follow-up
median 5.3 years
Funding
VITAL was supported by grants U01 CA138962 and R01 CA138962, which included support from the National Cancer Institute, National Heart, Lung and Blood Institute, Office of Dietary Supplements, National Institute of Neurological Disorders and Stroke, and the National Center for Complementary and Integrative Health. The NIH sponsors had a collaborative role in the design and conduct of the study and interpretation of the data; final decisions concerning these, data collection, management, analysis, review or approval of the manuscript and the decision to submit resided with the study investigators.
In-kind support
Pronova BioPharma and BASF donated Omacor fish oil, matching placebos and calendar packaging; Pharmavite donated vitamin D3; Quest Diagnostics measured the plasma omega-3 index at no cost.
Finding
Fish-oil capsule 1 g/day containing 840 mg n-3 fatty acids (EPA 460 mg, DHA 380 mg) versus placebo, median 5.3 years. Major cardiovascular events (myocardial infarction, stroke, cardiovascular death) 386 of 12,933 versus 419 of 12,938 (HR 0.92, 95% CI 0.80 to 1.06); invasive cancer 820 versus 797 (HR 1.03, 0.93 to 1.13); death from any cause 493 versus 485 (HR 1.02, 0.90 to 1.15). Total myocardial infarction, a secondary outcome, 145 versus 200 (HR 0.72, 0.59 to 0.90); there was no control for multiple hypothesis testing. Mean plasma omega-3 index 2.67% at baseline (15,535 participants), rising to 4.13% at 1 year in the active group (1583 participants).
Independent research
Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, et al. Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals JAMA Cardiology, 2018.
doi:10.1001/jamacardio.2017.5205 PubMed 29387889
Funding and finding
Participants
77,917
Follow-up
mean 4.4 years
Funding
This work was supported by grant CH/1996001/9454 from the British Heart Foundation, a grant from British Heart Foundation Centre for Research Excellence Oxford, and support from Medical Research Council Clinical Trial Service Unit A310 support to the Medical Research Council Public Health Research Unit at the Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Finding
Aggregated study-level data; EPA 226 to 1800 mg/day; 12,001 major vascular events. Rate ratios: major vascular events 0.97 (95% CI 0.93 to 1.01); any coronary heart disease event 0.96 (0.90 to 1.01); coronary heart disease death 0.93 (99% CI 0.83 to 1.03); nonfatal myocardial infarction 0.97 (99% CI 0.87 to 1.08); stroke 1.03 (0.93 to 1.13). No significant association with major vascular events in any prespecified subgroup, including prior coronary heart disease, diabetes, triglyceride level and statin use.
Industry-funded
ASCEND Study Collaborative Group; Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, et al. Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus New England Journal of Medicine, 2018.
doi:10.1056/NEJMoa1804989 PubMed 30146932
Funding and finding
Registration
ISRCTN60635500; NCT00135226
Participants
15,480
Follow-up
mean 7.4 years
Funding
Supported by grants to the University of Oxford from the British Heart Foundation; the Clinical Trial Service Unit receives support from the UK Medical Research Council, the British Heart Foundation and Cancer Research UK. Capsules containing the n-3 fatty acids and matching placebo, along with funding for packaging, were provided by Mylan (and formerly by Solvay and Abbott), and Bayer provided aspirin and placebo; the companies and Bayer U.S. provided some funding for drug packaging. Mylan, Solvay and Abbott had nonvoting representation at steering committee meetings and provided comments regarding the trial design and draft manuscript but otherwise had no role in data collection or analysis or in the decision to submit.
In-kind support
n-3 fatty acid and olive-oil placebo capsules from Solvay, Abbott and Mylan; aspirin and placebo tablets from Bayer.
Finding
1-g capsule with 840 mg marine n-3 fatty acids (EPA 460 mg, DHA 380 mg) versus olive oil daily, 7740 patients per group, mean follow-up 7.4 years, adherence 76%. First serious vascular event 689 (8.9%) versus 712 (9.2%) (rate ratio 0.97, 95% CI 0.87 to 1.08); serious vascular event or revascularisation 882 (11.4%) versus 887 (11.5%) (1.00, 0.91 to 1.09); death from any cause 752 (9.7%) versus 788 (10.2%) (0.95, 0.86 to 1.05). In exploratory analyses, vascular death excluding intracranial haemorrhage 186 (2.4%) versus 228 (2.9%) (0.81, 0.67 to 0.99); intervals for secondary and exploratory outcomes were not adjusted for multiple comparisons.
Industry-funded
Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia New England Journal of Medicine, 2019.
doi:10.1056/NEJMoa1812792 PubMed 30415628
Funding and finding
Registration
NCT01492361
Participants
8,179
Follow-up
median 4.9 years
Funding
Supported by Amarin Pharma. The steering committee of academic physicians and representatives of the sponsor developed the protocol and were responsible for the conduct and oversight of the study and interpretation of the data. The sponsor was responsible for the collection and management of the data, and all the data analyses were performed by the sponsor; the adjudicated end-point analyses were validated by an independent statistician from the data and safety monitoring committee.
Finding
Icosapent ethyl 2 g twice daily versus a placebo containing mineral oil. Primary composite (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularisation or unstable angina) 17.2% versus 22.0% (HR 0.75, 95% CI 0.68 to 0.83), absolute difference 4.8 percentage points (3.1 to 6.5), number needed to treat 21 (15 to 33) over a median 4.9 years; cardiovascular death, nonfatal myocardial infarction or nonfatal stroke 11.2% versus 14.8% (HR 0.74, 0.65 to 0.83), number needed to treat 28; cardiovascular death 4.3% versus 5.2% (HR 0.80, 0.66 to 0.98); death from any cause 6.7% versus 7.6% (HR 0.87, 0.74 to 1.02). Median change from baseline in triglycerides -18.3% versus +2.2% (to 1 year) and in LDL cholesterol +3.1% versus +10.2%. Hospitalisation for atrial fibrillation or flutter 3.1% versus 2.1%; atrial fibrillation adverse events 5.3% versus 3.9%; serious bleeding 2.7% versus 2.1% (P=0.06). The authors state that if mineral oil in the placebo affected statin absorption in some patients, this might have contributed to the differences in outcomes, but that the relatively small differences in LDL cholesterol between the groups would not be likely to explain the 25% lower risk; a post hoc analysis suggested a similar lower risk whether or not LDL cholesterol rose in the placebo group.
Industry-funded
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.
doi:10.1001/jama.2020.22258 PubMed 33190147
Funding and finding
Registration
NCT02104817
Participants
13,078
Follow-up
median 42.0 months; stopped early for futility
Funding
The trial was funded by AstraZeneca AB and coordinated by the Cleveland Clinic Coordinating Center for Clinical Research (C5Research). The sponsor participated actively in designing the study in collaboration with the steering committee, provided logistical support and maintained the trial database; statistical analyses were performed at C5Research by an independent statistician on a copy of the database; the sponsor was permitted to review the manuscript and make suggestions, and final decisions on content were retained by the academic authors.
Finding
Omega-3 carboxylic acids (EPA and DHA) 4 g/day versus corn oil, 6539 per group. Primary composite (cardiovascular death, myocardial infarction, stroke, coronary revascularisation or hospitalisation for unstable angina) 785 (12.0%) versus 795 (12.2%) (HR 0.99, 95% CI 0.90 to 1.09); cardiovascular death, myocardial infarction or stroke 541 (8.3%) versus 517 (7.9%) (HR 1.05, 0.93 to 1.19); death from any cause 373 (5.7%) versus 333 (5.1%). New-onset atrial fibrillation 2.2% versus 1.3% (HR 1.69, 1.29 to 2.21), number needed to harm 114; gastrointestinal adverse events 24.7% versus 14.7%. Triglycerides -19.0% versus -0.9%, hs-CRP -20.0% versus -6.3%, LDL cholesterol +1.2% versus -1.1%. The authors cite concerns over a greater than 30% increase in CRP in the mineral-oil group of REDUCE-IT, report that adverse effects on apolipoprotein B, LDL cholesterol and hs-CRP seen with mineral oil were not observed with corn oil, and state that these effects may have contributed to the apparent benefit of icosapent ethyl.
Expert consensus
National Institute for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification National Institute for Health and Care Excellence, NICE guideline NG238, 2023.
PubMed 38564551
Funding and finding
Funding
not stated
Finding
Recommendation 1.12.5: do not offer omega-3 fatty acid compounds to prevent cardiovascular disease; icosapent ethyl used as described in technology appraisal TA805 is an exception [2014, amended December 2023]. Recommendation 1.12.6: tell people that there is no evidence that omega-3 fatty acid compounds help to prevent cardiovascular disease, except icosapent ethyl as described in TA805. Recommendation 1.12.7: do not offer the combination of a statin with an omega-3 fatty acid compound, except icosapent ethyl as described in TA805.
Expert consensus
National Institute for Health and Care Excellence. Icosapent ethyl with statin therapy for reducing the risk of cardiovascular events in people with raised triglycerides National Institute for Health and Care Excellence, technology appraisal guidance TA805, 2022.
PubMed 40493729
Funding and finding
Funding
not stated
Finding
Icosapent ethyl is recommended as an option for reducing the risk of cardiovascular events in adults with a high risk of cardiovascular events, raised fasting triglycerides (1.7 mmol/litre or above) and statin treatment, only if they have established cardiovascular disease and LDL cholesterol above 1.04 mmol/litre and below or equal to 2.60 mmol/litre; it is unlikely to be cost effective for primary prevention and is not recommended for it. The company provided the clinical evidence from REDUCE-IT, whose placebo group took 4 g of light mineral oil a day. The committee concluded that the relative effect of icosapent ethyl was uncertain because of the potential negative effect of the mineral oil placebo, noted that STRENGTH, with a corn oil placebo, did not show the same magnitude of benefit, concluded that the mechanism of action is not fully understood, and considered scenarios reducing the treatment effect by 1.5% to 3%.

Updated 2026-10-21