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Cited by 46Fatty Acid Research and HealthNutritional Studies and DietAcute Ischemic Stroke Management

Omega-3 blood levels and stroke risk: a pooled and harmonized analysis of 183 291 participants from 29 prospective studies

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O’Keefe, James H., Tintle, Nathan L., Harris, William S., O’Keefe, Evan L., Sala-Vila, Aleix, Attia, John, Garg, G. Manohar, Hure, Alexis +64 more·2024·Stroke
DOI 10.1161/strokeaha.123.044281PMC PMC10840378
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Abstract

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76–0.91]; P <0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74–0.91]; P <0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81–0.96]; P =0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78–0.95]; P =0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

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  • Observational studies consistently show that an O3I of ≥8% is ideal for reducing risk of major adverse cardiovascular events, stroke, and all-cause mortality.

    “Observational studies consistently show that an O3I of ≥8% is ideal for reducing risk of major adverse cardiovascular events116 (MACE), stroke20 and all-cause mortality117.”

    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 [20]

    The Results report lower total and ischemic stroke incidence at higher omega-3 levels, and the Discussion (p. 56) says the highest omega-3-index quintile had a median of about 8%, suggesting that ≥8% could be a cardioprotective goal. That supports the stroke-related association, but does not establish ≥8% as an ideal threshold for reducing stroke risk; the paper also found no association with hemorrhagic stroke. The citations attached to MACE and all-cause mortality are separate from this source's stroke citation. (LLM, conf=0.86)

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  • In a comprehensive meta-analysis of more than 180,000 subjects, patients in the top quintile of marine omega-3 blood levels had an 18% lower risk of ischemic stroke and no effect on hemorrhagic stroke compared to patients in the lowest quintile.

    “Specifically, a comprehensive meta-analysis (n > 180,000 subjects) found patients in the top quintile of marine omega-3 blood levels had an 18% lower risk of ischemic stroke, and no effect on hemorrhagic stroke compared to patients in the lowest quintile of omega-320.”

    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 [20]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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  • 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 [20]

  • Higher omega-3 intake and blood levels are associated with lower risk of stroke.

    “Considering that stroke is the major complication of AF, it is paradoxical that higher omega-3 intake and blood levels have been repeatedly associated with a lower risk of stroke.”

    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 [20]

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Authors
O’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., Venø, S. K., Chien, K.-L., Chen, Y.-Y. (., Egert, S., Feldreich, T. R., Ärnlöv, J., Lind, L., Forouhi, N. G., Geleijnse, J. M., Pertiwi, K., Imamura, F., de Mello Laaksonen, V., Uusitupa, W. M., Tuomilehto, J., Laakso, M., Lankinen, M. A., Laurin, D., Carmichael, P.-H., Lindsay, J., Leander, K., Laguzzi, F., Swenson, B. R., Longstreth, W. T., Manson, J. E., Mora, S., Cook, N. R., Marklund, M., Melo van Lent, D., Murphy, R., Gudnason, V., Ninomiya, T., Hirakawa, Y., Qian, F., Sun, Q., Hu, F., Ardisson Korat, A. V., Risérus, U., Lázaro, I., Samieri, C., Le Goff, M., Helmer, C., Steur, M., Voortman, T., Ikram, M. K., Tanaka, T., Das, J. K., Ferrucci, L., Bandinelli, S., Tsai, M., Guan, W., Garg, P., Verschuren, W. M. M., Boer, J. M. A., Biokstra, A., Virtanen, J., Wagner, M., Westra, J., Albuisson, L., Yamagishi, K., Siscovick, D. S., Lemaitre, R. N., & Mozaffarian, D.
Affiliations
  • University of Missouri–Kansas City (US)
  • Fatty Acid Research Institute (US)
  • University of South Dakota (US)
  • Saint Luke's Hospital (US)
  • Fatty Acid Research Institute (N.L.T., W.S.H., A.S.-V., J.W.), Sioux Falls, SD.
  • University of Newcastle Australia (AU)
  • The University of Newcastle, School of Biomedical Sciences and Pharmacy, Callaghan, Australia (J. Attia, G.M.G., A.H.).
  • Aalborg University Hospital (DK)
  • National Taiwan University (TW)
  • Taichung Veterans General Hospital (TW)
  • University of Bonn (DE)
  • Dalarna University (SE)
  • Karolinska Institutet (SE)
  • Uppsala University (SE)
  • University of Cambridge (GB)
  • Wageningen University & Research (NL)
  • Institute of Public Health and Clinical Nutrition (V.d.M.L., W.M.U., J.T., M.A.L., J.V.), School of Medicine, University of Eastern Finland, Kuopio, Finland.
  • University of Eastern Finland (FI)
  • CHU de Québec-Université Laval and VITAM Research Centers, Centre d’Excellence sur le Vieillissement de Québec, Canada (D.L., P.-H.C.).
  • University of Ottawa (CA)
  • University of Washington (US)
  • Departments of Neurology and Epidemiology (W.T.L.), University of Washington, Seattle.
  • Brigham and Women's Hospital (US)
  • Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas, San Antonio (D.M.v.L.).
  • University of British Columbia (CA)
  • Icelandic Heart Association (IS)
  • Kyushu University (JP)
  • Harvard University (US)
  • USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA (A.V.A.K.).
  • Hospital Del Mar (ES)
  • Bordeaux Population Health Research Centre, University of Bordeaux, France (C.S., M.L.G., C.H.).
  • Université de Bordeaux (FR)
  • Erasmus MC (NL)
  • National Institutes of Health (US)
  • Azienda Sanitaria di Firenze (IT)
  • University of Minnesota (US)
  • University of Southern California (US)
  • National Institute for Public Health and the Environment (NL)
  • University Hospital Bonn (DE)
  • University of Denver (US)
  • University of Tsukuba (JP)
  • New York Academy of Medicine (US)
  • Department of Medicine, University of Washington, Seattle (R.N.L.).
  • Tufts University (US)
Corresponding author
O’Keefe, James H.
ORCID
Venue
Stroke
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2024-01
Volume
55
Issue
1
Pages
50-58
ISSN
  • 0039-2499 (ISSN-L)
  • 1524-4628
DOI
10.1161/strokeaha.123.044281
PMC
PMC10840378
OpenAlex
W4390098821
Cited by
46
References
78
Citations by year
2026: 14 · 2025: 18 · 2024: 14
FWCI
8.07
Type
journal article
Language
en
Update notices
correction (2024-02-26)
Open access
Licence
other-oa
Locations
  • Stroke (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, other-oa)
  • Socio-Environmental Systems Modeling (submittedVersion, other-oa)
  • HAL (submittedVersion)
  • Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion)
  • VBN Forskningsportal (Aalborg Universitet) (submittedVersion, other-oa)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • Rivm (National Institute for Public Health and the Environment) (submittedVersion)
Funders
  • U.S. Department of Agriculture (58-1950-7-707)
  • Bill and Melinda Gates Foundation
  • Alzheimer's Association
  • Pfizer
  • AstraZeneca
  • Brigham and Women's Hospital
  • University of Southern California
  • Kaiser Permanente
  • Pharmavite
  • University of Missouri
  • University of Minnesota
  • Itä-Suomen Yliopisto
  • University of Washington
  • Université Laval
  • Johns Hopkins University
  • University of Ottawa
  • University of Missouri-Kansas City
  • University of Denver
  • University of South Dakota
  • Quest Diagnostics
  • Saint Luke's Health System
  • National Institute for Health and Care Research (NIHR202397)
  • University of New South Wales
  • Aalborg Universitet
  • Karen Elise Jensens Fond
  • Karolinska Institutet
  • Centre Hospitalier Universitaire de Québec
  • Astellas Pharma
  • Deutsches Zentrum für Neurodegenerative Erkrankungen
  • Högskolan Dalarna
  • Université de Bordeaux
  • Aalborg Universitetshospital
  • National Taiwan University
  • Uppsala Universitet
  • Rheinische Friedrich-Wilhelms-Universität Bonn
  • Taichung Veterans General Hospital
  • National Institutes of Health (KL2TR002545)
  • Agricultural Research Service (581950-7-707)
  • Johns Hopkins Bloomberg School of Public Health
  • Medical Research Council
  • Wageningen University and Research
  • National Heart, Lung, and Blood Institute (T32HL110837, R01HL160799)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK112940)
  • National Center for Advancing Translational Sciences
  • National Center for Complementary and Integrative Health (R01AT011729)
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
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
Keywords
omega-3 polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid, stroke risk, ischemic stroke, hemorrhagic stroke, prospective cohort, pooled analysis, atrial fibrillation, cardiovascular disease
MeSH terms
Ischemic Stroke, Hemorrhagic Stroke, Docosahexaenoic Acids, Humans, Prospective Studies, Risk Factors, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Stroke

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