Omega-3 and omega-6 polyunsaturated fatty acid biomarkers and sleep: A pooled analysis of cohort studies

Authors: MURPHY, RACHEL - University Of British Columbia; TINTLE, NATHAN - Dordt College; HARRIS, WILLIAM - University Of South Dakota; DARVISHIAN, MARYAM - Bc Cancer Agency; MARKLUND, MATTI - University Of New South Wales; VIRTANEN, JYRKI - University Of Eastern Finland; HANTUNEN, SARI - University Of Eastern Finland; DE MELLO, VANESSA - University Of Eastern Finland; TUOMILEHTO, JAAKO - University Of Helsinki; LINDSTROM, JAANA - Finnish Institute For Health And Welfare; BOLT, MATTHEW - Dordt College; BROUWER, INGEBORG - Vrije University; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); SENN, MACKENZIE - Children'S Nutrition Research Center (CNRC); REDLINE, SUSAN - Harvard Medical School; TSAI, MICHAEL - University Of Minnesota; GUDNASON, VILMUNDUR - Icelandic Heart Association; EIRIKSDOTTIR, GUDNY - Icelandic Heart Association; LINDBERG, EVA - Uppsala University; SHADYAB, ALADDIN - University Of California, San Diego; LIU, BUYUN - University Of Iowa; CARNETHON, MERCEDES - Northwestern University; UUSITUPA, MATTI - University Of Eastern Finland; DJOUSSE, LUC - Brigham & Women'S Hospital; RISERUS, ULF - Uppsala University; LIND, LARS - Uppsala University; VAN DAM, ROB - National University Of Singapore; KOH, WOON - National University Of Singapore; SHI, PEILIN - Friedman School At Tufts; SISCOVICK, DAVID - New York Academy Of Medicine; LEMAITRE, ROZENN - University Of Washington; MOZAFFARIAN, DARIUSH - Friedman School At Tufts

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/30/2021
Publication Date: 12/16/2021
Citation: Murphy, R.A., Tintle, N., Harris, W.S., Darvishian, M., Marklund, M., Virtanen, J.K., Hantunen, S., de Mello, V.D., Tuomilehto, J., Lindstrom, J., Bolt, M.A., Brouwer, I.A., Wood, A.C., Senn, M., Redline, S., Tsai, M.Y., Gudnason, V., Eiriksdottir, G., Lindberg, E., Shadyab, A.H., Liu, B., Carnethon, M., Uusitupa, M., Djousse, L., Riserus, U., Lind, L., van Dam, R.M., Koh, W.P., Shi, P., Siscovick, D., Lemaitre, R.N., Mozaffarian, D. 2021. Omega-3 and omega-6 polyunsaturated fatty acid biomarkers and sleep: A pooled analysis of cohort studies. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqab408.
DOI: https://doi.org/10.1093/ajcn/nqab408

Interpretive Summary: Regularly experiencing a low duration, or a low quality, of sleep is emerging as an important cause of overweight/obesity. Two types of fat found in blood, known as n-3 and n-6 polyunsaturated fatty acids (PUFAs), have physiologic roles in sleep processes. One source of this fat is our diet, but little is known about whether dietary intake of n-3 and n-6 PUFA is associated with sleep quality. We examined this question using data from over 25,000 adults participating in 13 large-scale studies from around the world. Our analyses found that adults who consumed more n-3 PUFAs in their diet had a shorter sleep duration than those who consumed less. We did not find any associations between sleep duration or quality and the amount of n-6 PUFAs consumed. If additional studies confirm these conclusions, and use methods that can examine whether the observed association is causal, this information might eventually help us increase how long individuals tend to sleep and ultimately, alongside other interventions, contribute to reducing the prevalence of overweight/obesity in the population.

Technical Abstract: n-3 and n-6 polyunsaturated fatty acids (PUFAs) have physiologic roles in sleep processes, but little is known regarding circulating n-3 and n-6 PUFA and sleep parameters. The objective of the study was 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. Harmonized, de novo, individual-level analyses were performed and pooled across 12 cohorts. Participants were between 35 to 96 years old and from 5 nations. Circulating measures included alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), EPA+DPA+DHA, linoleic acid and arachidonic acid. Sleep duration (10 cohorts, N=18,791) was categorized as short (<=6 hours), 7-8 hours (reference) or long (9+ hours). Difficulty falling sleeping (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 odds ratios (ORs) per quintile of PUFAs were pooled with inverse-variance weighted meta-analysis. In pooled analysis adjusted for sociodemographics and health status, participants with higher very long-chain n-3 PUFAs were less likely to have long sleep duration. Comparing top vs. bottom quintiles, the multivariable-adjusted OR (95% confidence interval, CI) for long-sleep was 0.78 (0.65, 0.95) for DHA and for EPA+DPA+DHA, 0.76 (0.63, 0.93). Significant associations were not identified for ALA and n-6 PUFA with short sleep duration, or difficulty falling sleeping. Participants with higher levels 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 relationship. These novel findings across 12 cohorts highlight the need for experimental and biological assessments of very long-chain n-3 PUFAs and sleep duration.