Use of supplemental long-chain omega-3 fatty acids and risk for cardiac death: An updated meta-analysis and review of research gaps
Open accessAbstract
Background Randomized controlled trials (RCTs) assessing use of long-chain omega-3 polyunsaturated fatty acids (LC-OM3), primarily eicosapentaenoic acid, and/or docosahexaenoic acid have shown mixed results. Objective The objectives of the study were to update and further explore the available RCT data regarding LC-OM3 supplementation and risk for cardiac death and to propose testable hypotheses for the mixed results obtained in RCTs regarding supplemental LC-OM3 use and cardiac risk. Methods A literature search was conducted using PubMed and Ovid/MEDLINE for RCTs assessing LC-OM3 supplements or pharmaceuticals with intervention periods of at least 6 months and reporting on the outcome of cardiac death. Meta-analysis was used to compare cumulative frequencies of cardiac death events between the LC-OM3 and control groups, including sensitivity and subset analyses. Results Fourteen RCTs were identified for the primary analysis (71,899 subjects). In the LC-OM3 arms, 1613 cardiac deaths were recorded (4.48% of subjects), compared with 1746 cardiac deaths in the control groups (4.87% of subjects). The pooled relative risk estimate showed an 8.0% (95% confidence interval 1.6%, 13.9%, P = .015) lower risk in the LC-OM3 arms vs controls. Subset analyses showed numerically larger effects (12.9%–29.1% lower risks, all P < .05) in subsets of RCTs with eicosapentaenoic acid + docosahexaenoic acid dosages >1 g/d and higher risk samples (secondary prevention, baseline mean or median triglycerides ≥150 mg/dL, low-density lipoprotein cholesterol ≥130 mg/dL, statin use <40% of subjects). Heterogeneity was low (I 2 ≤ 15.5%, P > .05) for the primary and subset analyses. Conclusion LC-OM3 supplementation is associated with a modest reduction in cardiac death.
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A few meta-analyses found a statistically significant CVD risk reduction, but more results showed insufficient evidence of a possible protective effect.
“A few meta‐analyses found a statistically significant CVD risk reduction, 30 , 31 but more results showed insufficient evidence of a possible protective effect. 32 , 33 , 34 , 35 , 36 , 37”
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 [31]
The Results report a statistically significant 8.0% lower risk of cardiac death with supplemental long-chain omega-3 fatty acids in the primary meta-analysis. This supports the sentence’s significant-reduction finding, but only for cardiac death, not CVD risk broadly. The sentence assigns the insufficient-evidence finding to other citations. (LLM, conf=0.83)
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- Authors
- Maki, K. C., Palacios, O. M., Bell, M., & Toth, P. P.
- Affiliations
- MB Clinical Research and Consulting (United States) (US)
- Johns Hopkins University (US)
- Corresponding author
- Maki, Kevin C.
- Venue
- Journal of Clinical Lipidology
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 11
- Issue
- 5
- Pages
- 1152-1160.e2
- ISSN
- 1876-4789 (ISSN-L)
- 1933-2874
- OpenAlex
- W2741070947
- Cited by
- 107
- References
- 61
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 18 · 2020: 14 · 2019: 18 · 2018: 18 · 2017: 7 · 2014: 2
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of clinical lipidology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- 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
- n-3 long-chain polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid, omega-3 supplementation, cardiovascular mortality, cardiovascular risk, secondary prevention, triglycerides, LDL cholesterol, statin use, dose-response relationship
- MeSH terms
- Death, Humans, Risk, Fatty Acids, Omega-3, Randomized Controlled Trials as Topic, Dietary Supplements
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