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Serial circulating omega 3 polyunsaturated fatty acids and healthy ageing among older adults in the Cardiovascular Health Study: prospective cohort study

BMJ 2018; 363 doi: (Published 17 October 2018) Cite this as: BMJ 2018;363:k4067

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Omega 3 polyunsaturated acids and healthy ageing

  1. Heidi TM Lai, postdoctoral fellow1,
  2. Marcia C de Oliveira Otto, assistant professor2,
  3. Rozenn N Lemaitre, research associate professor3,
  4. Barbara McKnight, professor4,
  5. Xiaoling Song, senior staff scientist5,
  6. Irena B King, professor6,
  7. Paulo HM Chaves, associate professor7,
  8. Michelle C Odden, associate professor8,
  9. Anne B Newman, professor9,
  10. David S Siscovick, senior research scientist10,
  11. Dariush Mozaffarian, dean1
  1. 1Friedman School of Nutrition Science and Policy, Tufts University, 150 Harrison Avenue, Boston, MA 02111, USA
  2. 2Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA
  3. 3Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA
  4. 4Department of Biostatistics, University of Washington, Seattle, WA, USA
  5. 5Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  6. 6Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA
  7. 7Benjamin Leon Center for Geriatric Research and Education at Florida International University, Herbert Wertheim College of Medicine, Miami, FL, USA
  8. 8School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, USA
  9. 9Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
  10. 10The New York Academy of Medicine, New York City, NY, USA
  1. Correspondence to: H Lai Heidi.Lai{at} (or @heidilai03 on Twitter)
  • Accepted 10 September 2018


Objective To determine the longitudinal association between serial biomarker measures of circulating omega 3 polyunsaturated fatty acid (n3-PUFA) levels and healthy ageing.

Design Prospective cohort study.

Setting Four communities in the United States (Cardiovascular Health Study) from 1992 to 2015.

Participants 2622 adults with a mean (SD) age of 74.4 (4.8) and with successful healthy ageing at baseline in 1992-93.

Exposure Cumulative levels of plasma phospholipid n3-PUFAs were measured using gas chromatography in 1992-93, 1998-99, and 2005-06, expressed as percentage of total fatty acids, including α-linolenic acid from plants and eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid from seafoood.

Main outcome measure Healthy ageing defined as survival without chronic diseases (ie, cardiovascular disease, cancer, lung disease, and severe chronic kidney disease), the absence of cognitive and physical dysfunction, or death from other causes not part of the healthy ageing outcome after age 65. Events were centrally adjudicated or determined from medical records and diagnostic tests.

Results Higher levels of long chain n3-PUFAs were associated with an 18% lower risk (95% confidence interval 7% to 28%) of unhealthy ageing per interquintile range after multivariable adjustments with time-varying exposure and covariates. Individually, higher eicosapentaenoic acid and docosapentaenoic acid (but not docosahexaenoic acid) levels were associated with a lower risk: 15% (6% to 23%) and 16% (6% to 25%), respectively. α-linolenic acid from plants was not noticeably associated with unhealthy ageing (hazard ratio 0.92, 95% confidence interval 0.83 to 1.02).

Conclusions In older adults, a higher cumulative level of serially measured circulating n3-PUFAs from seafood (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid), eicosapentaenoic acid, and docosapentaenoic acid (but not docosahexaenoic acid from seafood or α-linolenic acid from plants) was associated with a higher likelihood of healthy ageing. These findings support guidelines for increased dietary consumption of n3-PUFAs in older adults.


  • Contributors: HTML, MCOO, RNL, BM, PHMC, MCO, ABN, DSS, and DM developed the study concept and design. HTML, MCOO, RNL, BM, XS, IBK, DSS, and DM contributed to the acquisition, analysis, and interpretation of data. HL conducted the statistical analysis. HL and DM wrote the first draft of the manuscript. All authors contributed to the critical revision of the manuscript for important intellectual content. DM, DSS, RNL and BM obtained the funding for the study data and analysis. HTML, MCOO, RNL, DSS, and DM provided administrative, technical and material support for the study analysis. DM is the study supervisor. All authors had full access to the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. HTML is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding: This research was supported by grant 2R01HL08571006A1 from the National Heart, Lung, and Blood Institute (NHLBI). The Cardiovascular Health Study was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grants U01HL080295 and U01HL130114 from the NHLBI, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by R01AG023629 from the National Institute on Ageing (NIA). A full list of principal Cardiovascular Health Study investigators and institutions can be found at The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The NHLBI also had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: Dr. Mozaffarian reports grants from NHLBI/NIH, during the conduct of the study; and personal fees from Global Organisation for EPA and DHA Omega-3s, DSM, Nutrition Impact, Pollock Communications, Bunge, Indigo Agriculture, Amarin, Acasti Pharma, and America’s Test Kitchen; scientific advisory board, Omada Health, Elysium Health, and DayTwo; and chapter royalties from UpToDate; all outside the submitted work. No other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: All protocols were approved at the institutional review board of each participating university.

  • Data sharing: No additional data are available.

  • Transparency: The manuscript’s guarantor affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned have been explained.

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