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Cited by 49Fatty Acid Research and HealthAtrial Fibrillation Management and OutcomesNutritional Studies and Diet

Omega-3 fatty acid biomarkers and incident atrial fibrillation

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Qian, Frank, Tintle, Nathan, Jensen, Paul N., Lemaitre, Rozenn N., Imamura, Fumiaki, Feldreich, Tobias Rudholm, Nomura, Sarah Oppeneer, Guan, Weihua +40 more·2023·Journal of the American College of Cardiology
DOI 10.1016/j.jacc.2023.05.024
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Abstract

Background The relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial. Objectives This study aimed to determine the prospective associations of blood or adipose tissue levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF. Methods We used participant-level data from a global consortium of 17 prospective cohort studies, each with baseline data on blood or adipose tissue omega-3 fatty acid levels and AF outcomes. Each participating study conducted a de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcome, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. Results Among 54,799 participants from 17 cohorts, 7,720 incident cases of AF were ascertained after a median 13.3 years of follow-up. In multivariable analysis, EPA levels were not associated with incident AF, HR per interquintile range (ie, the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively. Conclusions In vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AF. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AF risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained.

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Crossref · 10.1016/j.jacc.2023.05.024

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  • Higher circulating levels of marine omega-3 FAs suggest a potential protective impact of low to intermediate doses known to produce such blood levels.

    “suggesting a potential protective impact of low to intermediate doses known to produce such blood levels4.”

    From Effects of Omega-3 Fatty Acid Treatment on Risk for Atrial Fibrillation: An Updated Meta-Analysis of 35 Trials including 114 592 Individuals (2026) · cites this paper as [4]

    The Central Illustration reports a 6%–13% lower atrial-fibrillation risk in the highest versus lowest quintile of blood or tissue omega-3 levels, and the Discussion says those levels largely reflect habitual dietary intake. The paper does not establish that low-to-intermediate doses produce those specific blood levels or that giving such doses has a protective effect; its finding is observational. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • An omega-3 dose threshold of 1500 mg/day distinguishes intakes achievable through diet or dietary supplements from those requiring pharmacological formulations.

    “Omega-3 dose was categorized as ≤1500 mg/day or >1500 mg/day to distinguish intakes achievable through diet or dietary supplements from those requiring pharmacological formulations.”

    From Effects of Omega-3 Fatty Acid Treatment on Risk for Atrial Fibrillation: An Updated Meta-Analysis of 35 Trials including 114 592 Individuals (2026) · cites this paper as [4]

    The Discussion (page unavailable) contrasts habitual dietary intake, averaging 0.43 g/day in the countries studied, with more than 1.8 g/day added in high-dose trials. It does not establish a 1,500 mg/day cutoff or say that intakes above it require pharmacological formulations. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Upper quintile levels of the omega-3 index have been associated with the lowest risk of AF, stroke, and all-cause mortality in large long-term epidemiological studies.

    “which have been associated with the lowest risk of AF4, 19, stroke20, and all-cause mortality21 in large long-term epidemiological studies.”

    From Effects of Omega-3 Fatty Acid Treatment on Risk for Atrial Fibrillation: An Updated Meta-Analysis of 35 Trials including 114 592 Individuals (2026) · cites this paper as [4]

    The Central Illustration reports lower AF risk in the highest versus lowest quintile of blood or tissue omega-3 levels in 17 cohorts followed for a median of 13.3 years. The ‘Association with incident atrial fibrillation’ section also reports lower AF incidence with higher EPA+DHA. The paper does not establish that the highest quintile of the specifically named omega-3 index had the lowest risk among all quintiles. Stroke and all-cause mortality have separate citations in the citing sentence and are not assessed here. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • A 2023 biomarker-based meta-analysis of 17 prospective cohorts found that higher circulating levels of marine omega-3 FAs were inversely associated with incident AF.

    “a 2023 biomarker-based meta-analysis of 17 prospective cohorts found that higher circulating levels of marine omega-3 FAs were inversely associated with incident AF”

    From Effects of Omega-3 Fatty Acid Treatment on Risk for Atrial Fibrillation: An Updated Meta-Analysis of 35 Trials including 114 592 Individuals (2026) · cites this paper as [4]

    The Abstract reports a pooled analysis of 17 prospective cohorts and inverse associations of higher DPA, DHA, and EPA+DHA biomarker levels with incident AF. But EPA alone was not associated with incident AF, so the claim overgeneralizes the inverse association to marine omega-3 fatty acids as a whole. The study also measured biomarkers in blood or adipose tissue, not only circulating levels. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Higher omega-3 blood levels are associated with lower risk for AF.

    “in addition to a lower risk for AF4, 19”

    From Effects of Omega-3 Fatty Acid Treatment on Risk for Atrial Fibrillation: An Updated Meta-Analysis of 35 Trials including 114 592 Individuals (2026) · cites this paper as [4]

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Authors
Qian, F., Tintle, N., Jensen, P. N., Lemaitre, R. N., Imamura, F., Feldreich, T. R., Nomura, S. O., Guan, W., Laguzzi, F., Kim, E., Virtanen, J. K., Steur, M., Bork, C. S., Hirakawa, Y., O'Donoghue, M. L., Sala-Vila, A., Ardisson Korat, A. V., Sun, Q., Rimm, E. B., Psaty, B. M., Heckbert, S. R., Forouhi, N. G., Wareham, N. J., Marklund, M., Risérus, U., Lind, L., Ärnlöv, J., Garg, P., Tsai, M. Y., Pankow, J., Misialek, J. R., Gigante, B., Leander, K., Pester, J. A., Albert, C. M., Kavousi, M., Ikram, A., Voortman, T., Schmidt, E. B., Ninomiya, T., Morrow, D. A., Bayés-Genís, A., O’Keefe, J. H., Ong, K. L., Wu, J. H. Y., Mozaffarian, D., Harris, W. S., & Siscovick, D. S.
Affiliations
  • Beth Israel Deaconess Medical Center (US)
  • Dordt University (US)
  • University of Washington (US)
  • University of Cambridge (GB)
  • Dalarna University (SE)
  • University of Minnesota (US)
  • Karolinska Institutet (SE)
  • University of Eastern Finland (FI)
  • Erasmus MC (NL)
  • Aalborg University Hospital (DK)
  • Kyushu University (JP)
  • Brigham and Women's Hospital (US)
  • Harvard University (US)
  • Tufts University (US)
  • Uppsala University (SE)
  • University of Southern California (US)
  • Cedars-Sinai Medical Center (US)
  • Aalborg University (DK)
  • The University of Sydney (AU)
  • UNSW Sydney (AU)
  • University of South Dakota (US)
  • New York Academy of Medicine (US)
ORCID
Venue
Journal of the American College of Cardiology
Publisher
Elsevier BV
Published
2023-07
Volume
82
Issue
4
Pages
336-349
ISSN
0735-1097 (ISSN-L)
DOI
10.1016/j.jacc.2023.05.024
OpenAlex
W4384500936
Cited by
49
References
28
Citations by year
2026: 9 · 2025: 12 · 2024: 21 · 2023: 7
FWCI
8.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the American College of Cardiology (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (acceptedVersion)
  • Socio-Environmental Systems Modeling (submittedVersion)
  • VBN Forskningsportal (Aalborg Universitet) (submittedVersion)
Funders
  • U.S. Department of Health and Human Services
  • Abbott Laboratories
  • Amgen
  • AstraZeneca
  • Boston Scientific Corporation
  • ARCA Biopharma
  • National Institute for Health and Care Research (NIHR202397)
  • European Commission
  • Ministry of Education, Culture, Sports, Science and Technology (JP21K10448, JP21K11725, JP21K07522, JP20K10503, JP19K07890, JP20K11020, JP21H03200, JP18K17925)
  • ZonMw
  • Svenska Forskningsrådet Formas
  • Erasmus Medisch Centrum
  • Ministry of Health, Labour and Welfare (20FA1002)
  • Vetenskapsrådet
  • Akademiska Sjukhuset
  • Forskningsrådet om Hälsa, Arbetsliv och Välfärd
  • Uppsala Universitet
  • National Institutes of Health
  • Japan Society for the Promotion of Science (21H03200, 19K07890, 20FA1002, 21K10448, 21K11725, 20K11020, 18K17925, 21K07522, 20K10503)
  • Instituto de Salud Carlos III
  • European Regional Development Fund
  • National Heart, Lung, and Blood Institute
  • National Center for Research Resources
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Keywords
omega-3 fatty acids, atrial fibrillation, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, EPA and DHA, adipose tissue fatty acids, blood fatty acid levels, incident atrial fibrillation risk, fish consumption, dietary guidelines
MeSH terms
Atrial Fibrillation, Docosahexaenoic Acids, Humans, Prospective Studies, Risk Factors, Eicosapentaenoic Acid, Biomarkers, Fatty Acids, Omega-3

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