PUFA ω-3 and ω-6 biomarkers and sleep: A pooled analysis of cohort studies on behalf of the Fatty Acids and Outcomes Research Consortium (FORCE)

Rachel A. Murphy, Nathan Tintle, William S. Harris, Maryam Darvishian, Matti Marklund, Jyrki K. Virtanen, Sari Hantunen, Vanessa D. De Mello, Jaakko Tuomilehto, Jaana Lindström, Matthew A. Bolt, Ingeborg A. Brouwer, Alexis C. Wood, Mackenzie Senn, Susan Redline, Michael Y. Tsai, Vilmundur Gudnason, Gudny Eiriksdottir, Eva Lindberg, Aladdin H. ShadyabBuyun Liu, Mercedes Carnethon, Matti Uusitupa, Luc Djousse, Ulf Risérus, Lars Lind, Rob M. Van Dam, Woon Puay Koh, Peilin Shi, David Siscovick, Rozenn N. Lemaitre, Dariush Mozaffarian

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: n-3 and n-6 PUFAs have physiologic roles in sleep processes, but little is known regarding circulating n-3 and n-6 PUFA and sleep parameters. Objectives: We sought to assess associations between biomarkers of n-3 and n-6 PUFA intake with self-reported sleep duration and difficulty falling sleeping in the Fatty Acids and Outcome Research Consortium. Methods: Harmonized, de novo, individual-level analyses were performed and pooled across 12 cohorts. Participants were 35-96 y old and from 5 nations. Circulating measures included α-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA), DHA, EPA + DPA + DHA, linoleic acid, and arachidonic acid. Sleep duration (10 cohorts, n = 18,791) was categorized as short (≤6 h), 7-8 h (reference), or long (≥9 h). Difficulty falling asleep (8 cohorts, n = 12,500) was categorized as yes or no. Associations between PUFAs, sleep duration, and difficulty falling sleeping were assessed by cross-sectional multinomial logistic regression using standardized protocols and covariates. Cohort-specific multivariable-adjusted ORs per quintile of PUFAs were pooled with inverse-variance weighted meta-analysis. Results: In pooled analysis adjusted for sociodemographic characteristics and health status, participants with higher very long-chain n-3 PUFAs were less likely to have long sleep duration. In the top compared with the bottom quintiles, the multivariable-adjusted ORs (95% CIs) for long sleep were 0.78 (95% CI: 0.65, 0.95) for DHA and 0.76 (95% CI: 0.63, 0.93) for EPA + DPA + DHA. Significant associations for ALA and n-6 PUFA with short sleep duration or difficulty falling sleeping were not identified. Conclusions: Participants with higher concentrations of very long-chain n-3 PUFAs were less likely to have long sleep duration. While objective biomarkers reduce recall bias and misclassification, the cross-sectional design limits assessment of the temporal nature of this relation. These novel findings across 12 cohorts highlight the need for experimental and biological assessments of very long-chain n-3 PUFAs and sleep duration.

Original languageEnglish (US)
Pages (from-to)864-876
Number of pages13
JournalAmerican Journal of Clinical Nutrition
Issue number3
StatePublished - Mar 1 2022

Bibliographical note

Funding Information:
Supported (in part) by the Institute for the Advancement of Food and Nutrition Sciences (IAFNS) (through an ILSI North America Lipid Committee grant). IAFNS is a nonprofit science organization that pools funding from industry and advances science through in-kind and financial contributions from private and public sector members. RAM was funded by the Canadian Cancer Society (704735) and the Michael Smith Foundation for Health Research (17644). Sources of support for each of the studies are provided in the Online Supplementary Material.

Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of the American Society for Nutrition.


  • biomarkers
  • diet
  • fatty acids
  • omega-3
  • public health
  • sleep quality

PubMed: MeSH publication types

  • Journal Article
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't


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