The DOI matches its Crossref record; 94 of the 94 references it cites were found in a registry or an index.
Marine n−3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer
Open accessAbstract
BACKGROUND: Higher intake of marine n-3 (also called omega-3) fatty acids has been associated with reduced risks of cardiovascular disease and cancer in several observational studies. Whether supplementation with n-3 fatty acids has such effects in general populations at usual risk for these end points is unclear. METHODS: (at a dose of 2000 IU per day) and marine n-3 fatty acids (at a dose of 1 g per day) in the primary prevention of cardiovascular disease and cancer among men 50 years of age or older and women 55 years of age or older in the United States. Primary end points were major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes) and invasive cancer of any type. Secondary end points included individual components of the composite cardiovascular end point, the composite end point plus coronary revascularization (expanded composite of cardiovascular events), site-specific cancers, and death from cancer. Safety was also assessed. This article reports the results of the comparison of n-3 fatty acids with placebo. RESULTS: A total of 25,871 participants, including 5106 black participants, underwent randomization. During a median follow-up of 5.3 years, a major cardiovascular event occurred in 386 participants in the n-3 group and in 419 in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P=0.24). Invasive cancer was diagnosed in 820 participants in the n-3 group and in 797 in the placebo group (hazard ratio, 1.03; 95% CI, 0.93 to 1.13; P=0.56). In the analyses of key secondary end points, the hazard ratios were as follows: for the expanded composite end point of cardiovascular events, 0.93 (95% CI, 0.82 to 1.04); for total myocardial infarction, 0.72 (95% CI, 0.59 to 0.90); for total stroke, 1.04 (95% CI, 0.83 to 1.31); for death from cardiovascular causes, 0.96 (95% CI, 0.76 to 1.21); and for death from cancer (341 deaths from cancer), 0.97 (95% CI, 0.79 to 1.20). In the analysis of death from any cause (978 deaths overall), the hazard ratio was 1.02 (95% CI, 0.90 to 1.15). No excess risks of bleeding or other serious adverse events were observed. CONCLUSIONS: Supplementation with n-3 fatty acids did not result in a lower incidence of major cardiovascular events or cancer than placebo. (Funded by the National Institutes of Health and others; VITAL ClinicalTrials.gov number, NCT01169259 .).
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In the citing paper
“although only REDUCE-IT has shown cardiovascular benefits (as discussed later) (14-17).”
From 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia (2021) · cites this paper as [16]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“butseverallargeclinicaltrialsfailed to demonstrate any cardiovascular benefit with administration of low doses of omega-3 fatty acids. 8,12,13”
From Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk (2020) · cites this paper as [13]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The STRENGTH, VITAL, ASCEND, ORIGIN, OMEGA, ALPHA-OMEGA, GISSI-HF and GISSI-P trials randomized patients to receive either a combination of EPA and DHA or placebo; yet only the GISSI trials noted a statistically significant effect on cardiovascular events and mortality [96–103].”
From Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention (2023) · cites this paper as [96]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“TheVitaminDandOmega-3Trial(VITAL), in which 13% of the participants had type 2 diabetes, supplementation with 1 g of omega-3 fatty acids did not result in a lower incidence of major cardiovascular events (305).”
From Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report (2019) · cites this paper as [305]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Clinical trials revealed that ω3 PUFA supplementation of <1 g/d resulted in a very limited reduction in atherosclerotic CVD risk of major vascular events and CVD‐caused deaths. 22 , 23 , 133 , 154”
From Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials (2023) · cites this paper as [23]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A limitation to the study is the inclusion rate of 26 % of screened candidates, which is relatively low compared to other n-3 PUFA trials not targeting elderly patients 30-33 .”
From Effects of n-3 Fatty Acid Supplements in Elderly Patients After Myocardial Infarction (2021) · cites this paper as [31]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“These studies showed inconsistent reductions in MACE.”
From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [89]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Multiple large studies conducted since then to examine the benefits of low-dose mixtures of EPA and DHA with more contemporary background therapy, including statin therapy, have failed to show any significant reduction in cardiovascular endpoints.”
From 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia (2021) · cites this paper as [16]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“However, other recent trials studying lower doses of omega-3 fatty acids in a broader range of patients failed to demonstrate significant reductions of total cardiovascular events. 12,13”
From Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk (2020) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“This may explain why EPA + DHA combination treatment in various trials did not demonstrate an effect on reducing cardiovascular risk. 23 , 24 , 25 , 133”
From Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials (2023) · cites this paper as [23]
The cited source says what the claim attributes to it.
In the citing paper
“Earlier trials such as GISSI-Prevenzione, ASCEND, VITAL, and OMEMI evaluated low-dose EPA/DHA mixtures primarily in primary prevention settings or post-MI patients, often without significant baseline TG elevation and with limited use of statins in earlier trials [87–90].”
From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [89]
The cited source says what the claim attributes to it.
In the citing paper
“The ASCEND (A Study of Cardiovascular Events in Diabetes) [3] and VITAL (Vitamin D and Omega-3 Trial) trials [5] using EPA+DHA did not signi fi cantly reduce the primary cardiovascular endpoints”
From Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis (2021) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“During a median follow-up of 5.3 years, there was no significant difference in the 2 primary endpoints of major cardiovascular events (a composite of MI, stroke, or death from cardiovascular causes) or invasive cancer of any type.”
From 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia (2021) · cites this paper as [16]
In the citing paper
“Contemporary studies were conducted with higher standards and consistently failed to demonstrate significant benefits.”
In the citing paper
“at lower doses (1 g/day) these agents have generally failed to show reduced ASCVD.50,51”
From Clinical review on triglycerides (2020) · cites this paper as [51]
In the citing paper
“Recently, a new selective PPAR-α modulator (pemafibrate) has been reported to have marked efficacy in reducing TRLs [317].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [317]
In the citing paper
“However, this trial showed that just 840 mg of combined EPA/DHA significantly reduced MI and major CHD events [63].”
From Update on Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Health (2022) · cites this paper as [63]
In the citing paper
“This study did not show that supplementing with n-3 fatty acids reduced the incidence of major CVD events (a composite of MI, stroke, and death from CVD causes) or invasive cancer.”
From Update on Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Health (2022) · cites this paper as [63]
In the citing paper
“Individuals with low baseline fish consumption (<1.5 servings/week) had decreased risk for total CV events (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.67 to 0.98).”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [61]
In the citing paper
“However, there was a 28% reduction in total MI, which emerged after the first year and continued throughout the trial.”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [61]
In the citing paper
“In the VITAL trial, omega-3 PUFAs did not significantly reduce the primary composite endpoint of major ASCVD events (MI, stroke, and CVD mortality).”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [61]
In the citing paper
“Black study participants experienced a 77% treatment-associated reduction in MI (HR: 0.23; 95% CI: 0.11 to 0.47), and derived an MI benefit irrespective of baseline fish intake.”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [61]
In the citing paper
“There were significant reductions in other pre-specified secondary outcomes, including a 17% reduced risk for total coronary heart disease (CHD) and a 50% reduction in fatal MI”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [61]
In the citing paper
“In the statin era, CVOTs of combination OM-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] have not shown reduction in cardiovascular disease (CVD) events.”
From Critical Differences Between Dietary Supplement and Prescription Omega-3 Fatty Acids: A Narrative Review (2020) · cites this paper as [11]
In the citing paper
“Additional factors that may influence CVOT findings include OM-3 dose, definition of primary composite CV endpoint, and study population.”
From Critical Differences Between Dietary Supplement and Prescription Omega-3 Fatty Acids: A Narrative Review (2020) · cites this paper as [11]
In the citing paper
“The total daily dose of OM-3 was much lower in VITAL and ASCEND (< 1 g/day total OM-3 per each 1-g capsule) than in REDUCE-IT (4 g/day high-purity Rx EPA).”
From Critical Differences Between Dietary Supplement and Prescription Omega-3 Fatty Acids: A Narrative Review (2020) · cites this paper as [11]
In the citing paper
“The primary composite CV endpoint varied between the studies (Table 1, see footnote); for example, in REDUCE-IT, coronary revascularization and unstable angina were included, in addition to CV death, nonfatal myocardial infarction, and nonfatal stroke.”
From Critical Differences Between Dietary Supplement and Prescription Omega-3 Fatty Acids: A Narrative Review (2020) · cites this paper as [11]
In the citing paper
“A 17% risk reduction was recorded for total coronary heart disease, versus placebo.”
From Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations (2021) · cites this paper as [53]
In the citing paper
“Indeed, while the primary outcome of the study, a reduction in major cardiovascular events (a composite of myocardial infarction, stroke, and death from cardiovascular causes), was not achieved with statistical significance, the analysis did demonstrate an 8% reduction in such events.”
From Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations (2021) · cites this paper as [53]
In the citing paper
“Interestingly for African-Americans, the study found a dramatic 77% reduction in heart attacks linked to daily omega-3 supplementation.”
From Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations (2021) · cites this paper as [53]
In the citing paper
“In people who do not consume the recommended 1 or 2 servings of fish a week, the n-3 LCPUFA supplementation was linked to a 40% reduction in heart attacks; however, among the subjects who followed the fish consumption recommendation, there was no such association.”
From Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations (2021) · cites this paper as [53]
In the citing paper
“The primary conclusion of the VITAL study was not positive regarding the effect of supplementation with n-3 LCPUFA on major cardiovascular events as the data failed to show a lower incidence of major cardiovascular events in the experimental group than in the placebo control group [53].”
From Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations (2021) · cites this paper as [53]
In the citing paper
“However, the secondary outcomes were highly relevant as omega-3 supplementation was associated with a reduction in total and fatal myocardial infarction risk by 28% and 50%, respectively.”
From Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations (2021) · cites this paper as [53]
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Metadata
- Authors
- Manson, J. E., Cook, N. R., Lee, I.-M., Christen, W., Bassuk, S. S., Mora, S., Gibson, H., Albert, C. M., Gordon, D., Copeland, T., D’Agostino, D., Friedenberg, G., Ridge, C., Bubes, V., Giovannucci, E. L., Willett, W. C., & Buring, J. E.
- Affiliations
- Brigham and Women's Hospital (US)
- From the Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School (J.E.M., N.R.C., I-M.L., W.C., S.S.B., S.M., H.G., C.M.A., D.G., T.C., D.D., G.F., C.R., V.B., E.L.G., W.C.W., J.E.B.), and the Departments of Epidemiology (J.E.M., N.R.C., I.-M.L., W.C.W., J.E.B.) and Nutrition (E.L.G., W.C.W.), Harvard T.H. Chan School of Public Health — all in Boston.
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2019-01-03
- Volume
- 380
- Issue
- 1
- Pages
- 23-32
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC6392053
- OpenAlex
- W2899720772
- Semantic Scholar
- bb3183c85d8686140abdf23d14174712153d2ed2
- Cited by
- 979
- References
- 94
- Citations by year
- 2026: 78 · 2025: 93 · 2024: 98 · 2023: 121 · 2022: 130 · 2021: 136 · 2020: 162 · 2019: 141
- FWCI
- 94.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R0 CA138962)
- National Cancer Institute
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Aquaculture Nutrition and Growth
- Keywords
- omega-3 fatty acids, cardiovascular disease prevention, cancer prevention, primary prevention, cardiovascular events, myocardial infarction, stroke, cancer mortality, coronary revascularization, dietary supplementation, cardiovascular risk reduction, cancer risk reduction, older adults, Black participants, cancer risk factors
- MeSH terms
- Aged, Cardiovascular Diseases, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasms, Fatty Acids, Omega-3, Incidence, Treatment Failure
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