Abstract
Introduction
Sleep is increasingly being viewed as an issue of public health concern, yet few epidemiologic studies have explored associations between sleep habits and metabolomic profile.
Objectives
To assess the association between sleep and blood metabolites.
Methods
We examined the association between sleep and 891 fasting plasma metabolites in a subgroup of 106 participants from the Dietary Approaches to Stop Hypertension (DASH)—Sodium feeding trial (1997–1999). We produced two sleep variables to analyze, sleep midpoint (median time between bedtime and waketime) and sleep duration, as well as bedtime and wake time. Metabolites were measured using liquid and gas chromatography, coupled with mass spectrometry. We assessed associations between sleep variables and log transformed metabolites using linear mixed-effects models. We combined the resulting p-values using Fisher’s method to calculate associations between sleep and 38 metabolic pathways.
Results
Sixteen pathways were associated (p < 0.05) with midpoint. Only the γ-glutamyl amino acid metabolism pathway reached Bonferroni-corrected threshold (0.0013). Eighty-three metabolites were associated with midpoint (FDR < 0.20). Similar associations were found for wake time. Neither bed time nor duration were strongly associated. The top metabolites (pathways given in brackets) associated with sleep were erythrulose (advanced glycation end-product) (positive association) and several γ-glutamyl pathway metabolites, including CMPF (fatty acid, dicarboxylate), isovalerate (valine, leucine and isoleucine and fatty acid metabolism) and HWESASXX (polypeptide) (inverse association).
Conclusion
Within our study, several metabolites that have previously been linked to inflammation and oxidative stress (processes involved in diseases such as cardiovascular disease and cancer) were found to be associated with sleep.
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Data Availability
The metabolomic data reported in this paper are available upon request.
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This work was supported by the Intramural Research Program of the National Institutes of Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services.
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RS-S conceived of the project idea. VG-D and IW undertook a literature review to support the study. All authors contributed to the analysis plan, the analysis undertaken, and the writing of the manuscript (as well as commenting upon and amending the final manuscript).
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Vanessa L. Z. Gordon-Dseagu, Andriy Derkach, Qian Xiao, Ishmael Williams, Joshua Sampson and Rachael Z. Stolzenberg-Solomon have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
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Gordon-Dseagu, V.L.Z., Derkach, A., Xiao, Q. et al. The association of sleep with metabolic pathways and metabolites: evidence from the Dietary Approaches to Stop Hypertension (DASH)—sodium feeding study. Metabolomics 15, 48 (2019). https://doi.org/10.1007/s11306-019-1472-y
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DOI: https://doi.org/10.1007/s11306-019-1472-y