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Cited by 133Fatty Acid Research and HealthAtrial Fibrillation Management and OutcomesNutritional Studies and Diet

Effect of Marine Omega-3 Fatty Acid and Vitamin D Supplementation on Incident Atrial Fibrillation: A Randomized Clinical Trial

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Albert, Christine M., Cook, Nancy R., Pester, Julie, Moorthy, M. Vinayaga, Ridge, Claire, Danik, Jacqueline S., Gencer, Baris, Siddiqi, Hasan K. +5 more·2021·JAMA
DOI 10.1001/jama.2021.1489PMC PMC7967086
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Abstract

Importance: Atrial fibrillation (AF) is the most common heart rhythm disturbance, continues to increase in incidence, and results in significant morbidity and mortality. The marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D have been reported to have both benefits and risks with respect to incident AF, but large-scale, long-term randomized trial data are lacking. Objective: To test the effects of long-term administration of marine omega-3 fatty acids and vitamin D on incident AF. Design, Setting, and Participants: An ancillary study of a 2 × 2 factorial randomized clinical trial involving 25 119 women and men aged 50 years or older without prior cardiovascular disease, cancer, or AF. Participants were recruited directly by mail between November 2011 and March 2014 from all 50 US states and were followed up until December 31, 2017. Interventions: Participants were randomized to receive EPA-DHA (460 mg/d of EPA and 380 mg/d of DHA) and vitamin D3 (2000 IU/d) (n = 6272 analyzed); EPA-DHA and placebo (n = 6270 analyzed); vitamin D3 and placebo (n = 6281 analyzed); or 2 placebos (n = 6296 analyzed). Main Outcomes and Measures: The primary outcome was incident AF confirmed by medical record review. Results: Among the 25 119 participants who were randomized and included in the analysis (mean age, 66.7 years; 50.8% women), 24 127 (96.1%) completed the trial. Over a median 5.3 years of treatment and follow-up, the primary end point of incident AF occurred in 900 participants (3.6% of study population). For the EPA-DHA vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.24; P = .19). For the vitamin D3 vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.25; P = .19). There was no evidence for interaction between the 2 study agents (P = .39). Conclusions and Relevance: Among adults aged 50 years or older, treatment with EPA-DHA or vitamin D3, compared with placebo, resulted in no significant difference in the risk of incident AF over a median follow-up of more than 5 years. The findings do not support the use of either agent for the primary prevention of incident AF. Trial Registration: ClinicalTrials.gov Identifiers: NCT02178410; NCT01169259.

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  • The VITAL Rhythm Study did not find a significant increased risk of incident atrial fibrillation with 1 g/day marine omega-3 fatty acids (460 mg EPA and 380 mg DHA) compared with placebo (HR 1.09, 95%CI 0.96-1.24, P=0.19).

    “The study with the largest number of AF events, the VITAL Rhythm Study, did not find a significant increased risk of incident AF with 1gram per day of marine omega-3 fatty acids (460 mg of eicosapentaenoic acid [EPA] and 380 mg of docosahexaenoic acid [DHA]) compared with placebo (HR 1.09, 95%CI 0.96–1.24, P=0.19).8”

    From Effect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis (2021) · cites this paper as [8]

    The Trial Design and Oversight section describes 840 mg/day of marine omega-3 fatty acids—460 mg EPA and 380 mg DHA—not 1 g/day of those fatty acids. The Omega-3 Fatty Acid Supplementation results report the claimed nonsignificant comparison with placebo (HR 1.09, 95% CI 0.96–1.24; P = .19). The Results section reports 900 confirmed AF events, consistent with the study's characterization as having the largest number of events among the trials discussed. (LLM, conf=0.88)

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  • In VITAL, the largest atrial fibrillation primary prevention randomized trial testing 1 g of omega-3 fatty acids, findings were neutral (HR 1.09, 95%CI 0.96-1.24, P=0.19) and did not support supplemental use for primary prevention of atrial fibrillation.

    “In the VITAL trial, the largest AF primary prevention randomized trial that tested 1 gr of omega-fatty acids, the findings were neutral (HR 1.09, 95%CI 0.96–1.24, P=0.19) and did not support the use of supplemental for the primary prevention of AF.”

    From Effect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis (2021) · cites this paper as [8]

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Authors
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., Mora, S., Buring, J. E., & Manson, J. E.
Affiliations
  • Cedars-Sinai Medical Center (US)
  • Brigham and Women's Hospital (US)
  • Harvard University (US)
  • Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
Corresponding author
Albert, Christine M.
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2021-03-16
Volume
325
Issue
11
Pages
1061
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2021.1489
PMC
PMC7967086
OpenAlex
W3136726675
Cited by
133
References
9
Citations by year
2026: 22 · 2025: 13 · 2024: 23 · 2023: 36 · 2022: 26 · 2021: 13
FWCI
15.61
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL116690, R01HL134811, T32HL007575, K24HL136852)
  • National Cancer Institute (U01CA138962, R01CA138962)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK112940)
  • National Center for Complementary and Integrative Health (R01AT011729)
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
atrial fibrillation, omega-3 fatty acids, eicosapentaenoic acid, docosahexaenoic acid, vitamin D3, dietary supplementation, incident atrial fibrillation, older adults, cardiovascular risk factors, blood pressure, hypertriglyceridemia, triglycerides, HDL cholesterol, LDL cholesterol, triglyceride to HDL cholesterol ratio
MeSH terms
Aged, Atrial Fibrillation, Cholecalciferol, Docosahexaenoic Acids, Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Vitamin D Deficiency, Vitamins, Eicosapentaenoic Acid, Treatment Failure, Dietary Supplements

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