Omega-3 and risk of atrial fibrillation: vagally-mediated double-edged sword
Open accessAbstract
Objective Studies regarding effects of omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on risk of atrial fibrillation (AF) have reported discordant results. The aim of this review is to clarify effects of marine omega-3 intake on risk of AF. Patients and methods A PubMed search was performed using terms: atrial fibrillation, omega-3, EPA, DHA, vagal tone. We summarized findings from randomized clinical trials (RCTs), epidemiology studies, and meta-analyses evaluating effects/associations of DHA + EPA on risk of AF. Also, vagal tone was explored as a mediator between omega-3 and risk of AF. Results Meta-analyses of 8 RCTs and 17 prospective cohort studies comprised of 83,112 and 54,799 individuals, respectively, investigated the link between omega-3 intake and incident AF. The RCTs reported that treatment with DHA and/or EPA was associated with a 24 % increased relative risk of AF (absolute risk 4.0 % vs 3.3 %; relative risk [RR] 1.24, 95 % confidence interval [CI] 1.11-1.38, p = 0.0002). This was dose-dependent; DHA + EPA doses of ∼1000 mg/d increased AF risk ∼12 %, whereas 1800 to 4000 mg/d increased AF risk by ∼50 %. In contrast, observational studies focused on DHA + EPA blood levels or dietary intake have generally reported that higher omega-3 levels/consumption are associated with lower AF risk. Maximal AF risk reduction. (12 %) occurred at ∼650 mg/d of dietary DHA + EPA. Other studies have indicated that omega-3 fatty acids can dose-dependently increase vagal tone, which could explain the biphasic relationship between DHA + EPA and AF risk. Experimental studies show that low-level vagal stimulation decreases risk of AF, whereas high-level vagal stimulation increases risk of AF. Conclusion Higher consumption of dietary omega-3 is associated with decreased AF risk. In contrast, pharmaceutical dosing of omega-3 increases AF in a dose-dependent manner, which may be mediated by vagal tone.
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Dose-dependent vagal-stimulating effects of omega-3 are likely especially problematic for individuals at high risk for bradycardia-dependent AF, including endurance athletes, untreated obstructive sleep apnea, sick sinus syndrome, and chronically slow heart rates.
“The dose-dependent vagal-stimulating effects are likely to be especially problematic for individuals at high risk for bradycardia-dependent AF124. This includes individuals who perform high volumes of strenuous endurance exercise, patients with untreated obstructive sleep apnea, sick sinus syndrome and chronically slow heart rates124.”
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 [124]
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Cites
Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia
Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Doyle, R. T., Juliano, R. A., Jiao, L., Granowitz, C., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812792 · Cited by 3,317 · see citing works
Nicholls, S. J., Lincoff, A. M., Garcia, M., Bash, D., Ballantyne, C. M., Barter, P. J., Davidson, M. H., Kastelein, J. J. P., Koenig, W., McGuire, D. K., et al. (2020) · JAMA · doi:10.1001/jama.2020.22258 · Cited by 1,028 · see citing works
Effects of n−3 Fatty Acid Supplements in Diabetes Mellitus
The ASCEND Study Collaborative Group (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1804989 · Cited by 698 · see citing works
Stark, K. D., Van Elswyk, M. E., Higgins, M. R., Weatherford, C. A., & Salem, N. (2016) · Progress in Lipid Research · doi:10.1016/j.plipres.2016.05.001 · Cited by 519 · see citing works
n–3 Fatty Acids in Patients with Multiple Cardiovascular Risk Factors
The Risk and Prevention Study Collaborative Group (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1205409 · Cited by 510 · see citing works
Rimm, E. B., Appel, L. J., Chiuve, S. E., Djoussé, L., Engler, M. B., Kris-Etherton, P. M., Mozaffarian, D., Siscovick, D. S., Lichtenstein, A. H., & On behalf of the American Heart Association Nutrition Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Epidemiology and Prevention; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology (2018) · Circulation · doi:10.1161/cir.0000000000000574 · Cited by 500 · see citing works
Fish Intake and Risk of Incident Atrial Fibrillation
Mozaffarian, D., Psaty, B. M., Rimm, E. B., Lemaitre, R. N., Burke, G. L., Lyles, M. F., Lefkowitz, D., & Siscovick, D. S. (2004) · Circulation · doi:10.1161/01.cir.0000138154.00779.a5 · Cited by 456 · see citing works
Liu, L., & Nattel, S. (1997) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1997.273.2.h805 · Cited by 424 · see citing works
Effect of Fish Oil on Heart Rate in Humans: A Meta-Analysis of Randomized Controlled Trials
Mozaffarian, D., Geelen, A., Brouwer, I. A., Geleijnse, J. M., Zock, P. L., & Katan, M. B. (2005) · Circulation · doi:10.1161/circulationaha.105.556886 · Cited by 399 · see citing works
Bischoff-Ferrari, H. A., Vellas, B., Rizzoli, R., Kressig, R. W., da Silva, J. A. P., Blauth, M., Felson, D. T., McCloskey, E. V., Watzl, B., Hofbauer, L. C., et al. (2020) · JAMA · doi:10.1001/jama.2020.16909 · Cited by 353 · see citing works
Dai, H., Zhang, Q., Abu‐Much, A., Maor, E., Segev, A., Beinart, R., Adawi, S., Lu, Y., Bragazzi, N. L., & Wu, J. (2020) · European Heart Journal - Quality of Care and Clinical Outcomes · doi:10.1093/ehjqcco/qcaa061 · Cited by 330 · see citing works
Effects of n-3 Fatty Acid Supplements in Elderly Patients After Myocardial Infarction
Kalstad, A. A., Myhre, P. L., Laake, K., Tveit, S. H., Schmidt, E. B., Smith, P., Nilsen, D. W. T., Tveit, A., Fagerland, M. W., Solheim, S., et al. (2021) · Circulation · doi:10.1161/circulationaha.120.052209 · Cited by 311 · see citing works
TREAT AF (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation)
Stavrakis, S., Stoner, J. A., Humphrey, M. B., Morris, L. M., Filiberti, A., Reynolds, J. C., Elkholey, K., Javed, I., Twidale, N., Riha, P., et al. (2020) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2019.11.008 · Cited by 247 · see citing works
O’Keefe, J. H., Abuissa, H., Sastre, A., Steinhaus, D. M., & Harris, W. S. (2006) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2005.11.025 · Cited by 207 · see citing works
Self-citationBrouwer, I. A., Heeringa, J., Geleijnse, J. M., Zock, P. L., & Witteman, J. C. M. (2006) · American Heart Journal · doi:10.1016/j.ahj.2005.07.029 · Cited by 175 · see citing works
Frost, L., & Vestergaard, P. (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.1.50 · Cited by 172 · see citing works
Gencer, B., Djousse, L., Al-Ramady, O. T., Cook, N. R., Manson, J. E., & Albert, C. M. (2021) · Circulation · doi:10.1161/circulationaha.121.055654 · Cited by 150 · see citing works
Ardell, J. L., Nier, H. A., Hammer, M., Southerland, E. M., Ardell, C. L., Beaumont, É., KenKnight, B. H., & Armour, J. A. (2017) · The Journal of Physiology · doi:10.1113/jp274678 · Cited by 149 · see citing works
Dietary factors and incident atrial fibrillation: the Framingham Heart Study
Shen, J., Johnson, V. M., SULLIVAN, L. M., Jacques, P. F., Magnani, J. W., Lubitz, S. A., Pandey, S., Levy, D. A., Vasan, R. S., Quatromoni, P. A., et al. (2010) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.001305 · Cited by 133 · see citing works
Albert, C. M., Cook, N. R., Pester, J., Moorthy, M. V., Ridge, C., Danik, J. S., Gencer, B., Siddiqi, H. K., Ng, C., Gibson, H., et al. (2021) · JAMA · doi:10.1001/jama.2021.1489 · Cited by 133 · see citing works
Low-Level Vagosympathetic Stimulation
Li, S., Scherlag, B. J., Yu, L., Sheng, X., Zhang, Y., Ali, R., Dong, Y., Ghias, M., & Po, S. S. (2009) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.109.868331 · Cited by 122 · see citing works
Mariani, J. A., Doval, H. C., Nul, D. R., Varini, S. D., Grancelli, H., Ferrante, D., Tognoni, G., & Macchia, A. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.112.005033 · Cited by 107 · see citing works
Li, Z., Zhong, W.-F., Liu, S., Kraus, V. B., Zhang, Y.-J., Gao, X., Lv, Y., Shen, D., Zhang, X.-R., Zhang, P., et al. (2020) · BMJ · doi:10.1136/bmj.m456 · Cited by 102 · see citing works
Predicting the effects of supplemental EPA and DHA on the omega-3 index
Walker, R. E., Jackson, K. H., Tintle, N. L., Shearer, G. C., Bernasconi, A., Masson, S., Latini, R., Heydari, B., Kwong, R. Y., Flock, M., et al. (2019) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz161 · Cited by 93 · see citing works
Self-citationDietary Fish Intake and Incident Atrial Fibrillation (from the Women's Health Initiative)
Berry, J. D., Prineas, R. J., Horn, L. V., PASSMAN, R. S., Larson, J. C., Goldberger, J. J., Snetselaar, L. G., Tinker, L. F., Liu, K., & Lloyd‐Jones, D. M. (2010) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2009.11.039 · Cited by 77 · see citing works
Omega-3 Polyunsaturated Fatty Acids and Heart Rate Variability
Christensen, J. H. (2011) · Frontiers in Physiology · doi:10.3389/fphys.2011.00084 · Cited by 76 · see citing works
Association of reported fish intake and supplementation status with the omega-3 index
Jackson, K. H., Polreis, J., Tintle, N., Kris‐Etherton, P. M., & Harris, W. S. (2019) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2019.01.002 · Cited by 66 · see citing works
Self-citationZhang, Y., Ilsar, I., Sabbah, H. N., David, T. B., & Mazgalev, T. N. (2008) · Heart Rhythm · doi:10.1016/j.hrthm.2008.10.043 · Cited by 57 · see citing works
Red blood cell fatty acid patterns from 7 countries: focus on the Omega-3 Index
Schuchardt, J. P., Cerrato, M., Ceseri, M., DeFina, L. F., Delgado, G. E., Gellert, S., Hahn, A., Howard, B. V., Kadota, A., Kleber, M. E., et al. (2022) · Prostaglandins, Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2022.102418 · Cited by 56 · see citing works
Self-citationRix, T. A., Joensen, A. M., Riahi, S., Lundbye‐Christensen, S., Tjønneland, A. M., Schmidt, E. B., & Overvad, K. (2014) · EP Europace · doi:10.1093/europace/euu019 · Cited by 51 · see citing works
Omega-3 fatty acid biomarkers and incident atrial fibrillation
Qian, F., Tintle, N., Jensen, P. N., Lemaitre, R. N., Imamura, F., Feldreich, T. R., Nomura, S. O., Guan, W., Laguzzi, F., Kim, E., et al. (2023) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2023.05.024 · Cited by 49 · see citing works
Self-citationO’Keefe, J. H., Tintle, N. L., Harris, W. S., O’Keefe, E. L., Sala-Vila, A., Attia, J., Garg, G. M., Hure, A., Bork, C. S., Schmidt, E. B., et al. (2024) · Stroke · doi:10.1161/strokeaha.123.044281 · Cited by 46 · see citing works
Self-citationAleksova, A., Masson, S., Maggioni, A. P., Lucci, D., Fabbri, G., Beretta, L., Mos, L., Paino, A. M., Nicolosi, G. L., Marchioli, R., et al. (2013) · European Journal of Heart Failure · doi:10.1093/eurjhf/hft103 · Cited by 45 · see citing works
Vuoti, A. O., Tulppo, M. P., Ukkola, O. H., Junttila, J. M., Huikuri, H. V., Kiviniemi, A. M., & Perkiömäki, J. S. (2021) · PLoS ONE · doi:10.1371/journal.pone.0254107 · Cited by 31 · see citing works
Olshansky, B., Bhatt, D. L., Miller, M., Steg, P. G., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Doyle, R. T., Juliano, R. A., Jiao, L., et al. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.121.026756 · Cited by 29 · see citing works
Jia, X., Gao, F., Pickett, J. K., Al Rifai, M., Birnbaum, Y., Nambi, V., Virani, S. S., & Ballantyne, C. M. (2021) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-021-07204-z · Cited by 27 · see citing works
Circulating Docosahexaenoic Acid and Risk of All-Cause and Cause-Specific Mortality
O’Keefe, E. L., O’Keefe, J. H., Tintle, N., Westra, J., Albuisson, L., & Harris, W. S. (2024) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2023.11.026 · Cited by 24 · see citing works
Self-citationLarsson, S. C., & Wolk, A. (2016) · Clinical Nutrition · doi:10.1016/j.clnu.2016.01.019 · Cited by 23 · see citing works
Myhre, P. L., Berge, T., Kalstad, A. A., Tveit, S. H., Laake, K., Schmidt, E. B., Solheim, S., Arnesen, H., Seljeflot, I., & Tveit, A. (2023) · Clinical Nutrition · doi:10.1016/j.clnu.2023.07.002 · Cited by 19 · see citing works
Chiuve, S. E., Sandhu, R. K., Moorthy, M. V., Glynn, R. J., & Albert, C. M. (2015) · Journal of Nutrition · doi:10.3945/jn.115.212860 · Cited by 16 · see citing works
Lakkireddy, D. (2020) · Journal of Atrial Fibrillation · doi:10.4022/jafib.2410 · Cited by 15 · see citing works
Omega‐3 fatty acids in adipose tissue and risk of atrial fibrillation
Rix, T. A., Dinesen, P. T., Lundbye‐Christensen, S., Joensen, A. M., Riahi, S., Overvad, K., & Schmidt, E. B. (2021) · European Journal of Clinical Investigation · doi:10.1111/eci.13649 · Cited by 11 · see citing works
Dietary ω-3 fatty acids and the incidence of atrial fibrillation in the Million Veteran Program
Guardino, E. T., Li, Y., Nguyen, X. T., Wilson, P. W. F., Gaziano, J. M., Cho, K., Benjamin, E. J., & Djoussé, L. (2023) · American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2023.06.001 · Cited by 10 · see citing works
Christifano, D. N., Chollet-Hinton, L., Mathis, N. B., Gajewski, B. J., Carlson, S. E., Colombo, J., & Gustafson, K. M. (2022) · The Journal of Nutrition · doi:10.1093/jn/nxac178 · Cited by 10 · see citing works
Omega-3 Fatty Acids and Risk for Atrial Fibrillation
Ballantyne, C. M., & Jia, X. (2023) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2023.05.026 · Cited by 10 · see citing works
Tikkanen, J. T., Soliman, E. Z., Pester, J., Danik, J. S., Gomelskya, N., Copeland, T., Lee, I.-M. M., Buring, J. E., Manson, J. E., Cook, N. R., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-38344-x · Cited by 9 · see citing works
Zhang, J., Cai, A., Chen, G., Wang, X., Cai, M., Li, H., Nissen, S. E., Lip, G. Y. H., & Lin, H. (2022) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwac192 · Cited by 8 · see citing works
Higher omega-3 index is associated with more rapid heart rate recovery in healthy men and women
Farrell, S. W., DeFina, L. F., Tintle, N., Barlow, C. E., Leonard, D. S., Haskell, W. L., Berry, J. D., Willis, B. L., Pavlovic, A., & Harris, W. S. (2020) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2020.102206 · Cited by 7 · see citing works
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Research works printed but not linked: 1
- [4]Qian F, Tintle N, Lemaitre RN, Harris WS, O’Keefe JH, Mozaffarian D. Omega-3 fatty acids biomarkers and incident atrial fibrillaton: an individual participant-level pooled analysis of 17 international prospective studies. JACC. 2023; 82(4): 336– 349 37769813
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Mickiewicz, A., Żegleń, S., Kędzierska-Kapuza, K., Heleniak, Z., Frankiewicz, A., Adamczyk, E., Wełnicki, M. T., Wawrzynowicz‐Syczewska, M., Raszeja‐Wyszomirska, J., Durlik, M., et al. (2025) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfaf104 · Cited by 8 · see citing works
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Self-citationAbuknesha, N. R., O’Keefe, J. H., Qian, F., Tintle, N., Lin, Y., Sun, Y., Qian, H., Aisen, P. S. S., Albert, C. M., Aronson, W. J., et al. (2026) · Proceedings of The Nutrition Society · doi:10.1017/s0029665126102493 · Cited by 5 · see citing works
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“123 This includes individuals who perform high volumes of strenuous endurance exercise, patients with untreated obstructive sleep apnea, sick sinus syndrome, and chronically slow heart rates.”
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- Authors
- O'Keefe, E. L., O'Keefe, J. H., Abuissa, H., Metzinger, M., Murray, E., Franco, G., Lavie, C. J., & Harris, W. S.
- Affiliations
- Creighton University (US)
- University of Missouri–Kansas City (US)
- University of South Dakota (US)
- Venue
- Progress in Cardiovascular Diseases
- Publisher
- Elsevier BV
- Published
- 2025-07
- Volume
- 91
- Pages
- 3-9
- ISSN
- 0033-0620 (ISSN-L)
- PMC
- PMC12122841
- OpenAlex
- W4404875949
- Cited by
- 12
- References
- 53
- Citations by year
- 2026: 5 · 2025: 7
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- Licence
- Locations
- Progress in Cardiovascular Diseases (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute
- National Institutes of Health (T32HL110837)
- 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, eicosapentaenoic acid, docosahexaenoic acid, atrial fibrillation, vagal tone, dose-dependent effects, omega-3 supplementation, arrhythmia risk
- MeSH terms
- Atrial Fibrillation, Docosahexaenoic Acids, Heart Rate, Humans, Risk Factors, Vagus Nerve, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Risk Assessment, Dietary Supplements, Protective Factors
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