Amer J Clin Nutr., 2022., Mar 4;115(3):864-876. doi: 10.1093/ajcn/nqab408.

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).

Murphy RA Tintle N Harris WS et al.


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.

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Key Points

The lower likelihood of long sleep duration among individuals with higher concentrations of very long chain n-3 PUFAs may suggest potential positive effects on sleep consolidation/quality. It is unclear why very long-chain n-3 PUFAs were not associated with short sleep duration. It is possible our definition of short sleep duration (<7 h) compared with an alternative definition (e.g., <6 h) may have altered risk associations. These findings are, however, supported by a recent randomized trial of the effects of either DHA, EPA, or placebo on sleep in 84 healthy young adults that found that DHA supplementation produced shorter sleep latency (time to sleep onset) and greater sleep efficiency (time asleep/time in bed) compared with placebo, while a trend toward greater sleep efficiency with EPA supplementation was also observed

In this large, biomarker-based pooling project including 12 large studies from 5 nations, individuals with lower concentrations of very long-chain n-3 PUFAs were more likely to have sleep that exceeds the current recommended duration. These findings highlight the importance of continued study of very long-chain n-3 PUFAs and sleep given the health implications of poor sleep. There is also a need to determine the temporality of associations and to further understand the potential underlying biological mechanisms.