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Plasma Phospholipid Long-Chain ω-3 Fatty Acids and Total and Cause-Specific Mortality in Older Adults: A Cohort Study
Open accessAbstract
BACKGROUND: Long-chain ω-3 polyunsaturated fatty acids (ω3-PUFAs), including eicosapentaenoic acid (EPA) (20:5ω-3), docosapentaenoic acid (DPA) (22:5ω-3), and docosahexaenoic acid (DHA) (22:6ω-3), have been shown to reduce cardiovascular risk, but effects on cause-specific and total mortality and potential dose-responses remain controversial. Most observational studies have assessed self-reported dietary intake and most randomized trials have tested effects of adding supplements to dietary intake and evaluated secondary prevention, thus limiting inference for dietary ω3-PUFAs or primary prevention. OBJECTIVE: To investigate associations of plasma phospholipid EPA, DPA, DHA, and total ω3-PUFA levels with total and cause-specific mortality among healthy older adults not receiving supplements. DESIGN: Prospective cohort study. SETTING: 4 U.S. communities. PARTICIPANTS: 2692 U.S. adults aged 74 years (±5 years) without prevalent coronary heart disease (CHD), stroke, or heart failure at baseline. MEASUREMENTS: Phospholipid fatty acid levels and cardiovascular risk factors were measured in 1992. Relationships with total and cause-specific mortality and incident fatal or nonfatal CHD and stroke through 2008 were assessed. RESULTS: During 30 829 person-years, 1625 deaths (including 570 cardiovascular deaths), 359 fatal and 371 nonfatal CHD events, and 130 fatal and 276 nonfatal strokes occurred. After adjustment, higher plasma levels of ω3-PUFA biomarkers were associated with lower total mortality, with extreme-quintile hazard ratios of 0.83 for EPA (95% CI, 0.71 to 0.98; P for trend = 0.005), 0.77 for DPA (CI, 0.66 to 0.90; P for trend = 0.008), 0.80 for DHA (CI, 0.67 to 0.94; P for trend = 0.006), and 0.73 for total ω3-PUFAs (CI, 0.61 to 0.86; P for trend < 0.001). Lower risk was largely attributable to fewer cardiovascular than noncardiovascular deaths. Individuals in the highest quintile of phospholipid ω3-PUFA level lived an average of 2.22 more years (CI, 0.75 to 3.13 years) after age 65 years than did those in the lowest quintile. LIMITATION: Temporal changes in fatty acid levels and misclassification of causes of death may have resulted in underestimated associations, and unmeasured or imperfectly measured covariates may have caused residual confounding. CONCLUSION: Higher circulating individual and total ω3-PUFA levels are associated with lower total mortality, especially CHD death, in older adults. PRIMARY FUNDING SOURCE: National Institutes of Health.
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“circulating concentrations of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) inversely correlate with cardiovascular risk. 3,4”
From Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk (2020) · cites this paper as [3]
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“The potential value of omega-3 fatty acids was supported by epidemiological studies demonstrating aninverserelationship between circulating concentrations of omega-3fattyacidsandcardiovascularrisk. 3,4”
From Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk (2020) · cites this paper as [3]
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In the citing paper
“than corresponding values from population studies in the USA (0.5 % EPA and 2.9 % DHA) 35 , suggesting higher background consumption of n-3 PUFA in our Norwegian study population.”
From Effects of n-3 Fatty Acid Supplements in Elderly Patients After Myocardial Infarction (2021) · cites this paper as [35]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“It is also worth noting that the baseline median levels in our material (2.5 % EPA and 5.6 % DHA) are notably higher than corresponding values from population studies in the USA (0.5 % EPA and 2.9 % DHA) 35 , suggesting higher background consumption of n-3 PUFA in”
From Effects of n-3 Fatty Acid Supplements in Elderly Patients After Myocardial Infarction (2021) · cites this paper as [35]
Experimental — accuracy not yet measuredIn the citing paper
“Biomarker levels of these fatty acids are only moderately interrelated (eg, r = 0.43,0.51, and 0.13 for EPA and DHA, EPA and DPA, and DPA and DHA, respectively).41”
From ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies (2016) · cites this paper as [41]
In the citing paper
“Observational evidence supports the recommendation that the intake of fish (at least twice a week) and long chain n-3 fatty acids supplements at low dosage may reduce the risk of CV death and stroke in primary prevention, but have no major effects on plasma lipoprotein metabolism. 183”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [183]
In the citing paper
“Not enough data are available to make a recommendation regarding the optimal n-3:n-6 fatty acid ratio.182,183”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [183]
In the citing paper
“Observational evidence supports the recommendation that the intake of fish (at least twice a week) and long chain n-3 fatty acids supplements at low dosage may reduce the risk of CV death and stroke in primary prevention, but have no major effects on plasma lipoprotein metabolism.183”
From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [183]
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Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz455 · Cited by 8,961
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.08.014 · Cited by 4,854
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Catapano, A. L., Graham, I., De Backer, G., Wiklund, O., Chapman, M. J., Drexel, H., Hoes, A. W., Jennings, C. S., Landmesser, U., Pedersen, T. R., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw272 · Cited by 3,162
2016 ESC/EAS Guidelines for the Management of Dyslipidaemias
Catapano, A. L., Graham, I., De Backer, G., Wiklund, O., Chapman, M. J., Drexel, H., Hoes, A. W., Jennings, C. S., Landmesser, U., Pedersen, T. R., et al. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.08.018 · Cited by 1,582
Omega-3 polyunsaturated fatty acids and their health benefits
Shahidi, F., & Ambigaipalan, P. (2018) · Annual Review of Food Science and Technology · doi:10.1146/annurev-food-111317-095850 · Cited by 1,390
Metadata
- Authors
- Mozaffarian, D., Lemaitre, R. N., King, I. B., Song, X., Huang, H., Sacks, F. M., Rimm, E. B., Wang, M., & Siscovick, D. S.
- Affiliations
- Brigham and Women's Hospital (US)
- From Brigham and Women's Hospital, Harvard Medical School, and Harvard School of Public Health, Boston, Massachusetts; University of New Mexico, Albuquerque, New Mexico; and Fred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington.
- ORCID
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2013-04-02
- Volume
- 158
- Issue
- 7
- Pages
- 515-525
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- PMC
- PMC3698844
- OpenAlex
- W2015008724
- Cited by
- 283
- References
- 61
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 13 · 2023: 9 · 2022: 13 · 2021: 19 · 2020: 24 · 2019: 20 · 2018: 30 · 2017: 23 · 2016: 29 · 2015: 37 · 2014: 26 · 2013: 19
- FWCI
- 34.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (n01hc085082-026, n01hc085081-021, n01hc045133-001, n01hc085079-024, n01hc015103-009, n01hc085084-005, n01hc085085-011, n01hc085083-027, n01hc085080-026, n01hc085086-022, n01hc55222-0-0-0, n01hc075150-004, n01hc035129-010)
- National Institute on Aging (AG 20098, R56AG023629, R01AG020098, AG023629, AG027058, R56AG020098, R01AG023629, R01AG015928, R01AG027058)
- National Heart, Lung, and Blood Institute (N01-HC-85081, N01HC85085, N01 HC085086, N01HC-85083, N0-1-HC-85239, N01 HC085079, N01HC85082, N01HC‐75150, N01 HC85086, N01 HC035129, N01HC85080, N01 HC015103, N01 HC55222, HHSN268201200036C, U01HL080295, N01 HC055222, R01HL085710, HL080295, R01HL080295, N01 HC075150, N01 HC045133, N01-HC85079, N01-HC85084)
- 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
- plasma phospholipid fatty acids, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, all-cause mortality, cause-specific mortality, cardiovascular mortality, coronary artery disease, stroke, older adults, primary prevention, dietary fatty acids, dietary biomarkers, dose-response relationship
- MeSH terms
- Aged, Cause of Death, Coronary Disease, Docosahexaenoic Acids, Fatty Acids, Unsaturated, Feeding Behavior, Female, Humans, Male, Prospective Studies, Eicosapentaenoic Acid, Biomarkers, Fatty Acids, Omega-3, Diet Records, Risk Assessment, Stroke
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- CoChat. (2026). Citation check: Plasma Phospholipid Long-Chain ω-3 Fatty Acids and Total and Cause-Specific Mortality in Older Adults: A Cohort Study. https://app.cochat.ai/papers/10.7326/0003-4819-158-7-201304020-00003
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- Mozaffarian, D., Lemaitre, R. N., King, I. B., Song, X., Huang, H., Sacks, F. M., Rimm, E. B., Wang, M., & Siscovick, D. S. (2013). Plasma Phospholipid Long-Chain ω-3 Fatty Acids and Total and Cause-Specific Mortality in Older Adults: A Cohort Study. Annals of Internal Medicine. https://doi.org/10.7326/0003-4819-158-7-201304020-00003
