The human circadian metabolome
Open accessAbstract
The circadian clock orchestrates many aspects of human physiology, and disruption of this clock has been implicated in various pathologies, ranging from cancer to metabolic syndrome and diabetes. Although there is evidence that metabolism and the circadian clockwork are intimately linked on a transcriptional level, whether these effects are directly under clock control or are mediated by the rest–activity cycle and the timing of food intake is unclear. To answer this question, we conducted an unbiased screen in human subjects of the metabolome of blood plasma and saliva at different times of day. To minimize indirect effects, subjects were kept in a 40-h constant routine of enforced posture, constant dim light, hourly isocaloric meals, and sleep deprivation. Under these conditions, we found that ∼15% of all identified metabolites in plasma and saliva were under circadian control, most notably fatty acids in plasma and amino acids in saliva. Our data suggest that there is a strong direct effect of the endogenous circadian clock on multiple human metabolic pathways that is independent of sleep or feeding. In addition, they identify multiple potential small-molecule biomarkers of human circadian phase and sleep pressure.
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Dallman et al. found 33 of 40 lipid species regulated in a circadian manner, with carnitine C12:0 overlapping with this study.
“Dallman et al. (12) found that 33 of 40 lipid species were regulated in a circadian manner, of which carnitine C12:0 overlaps with our study.”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [12]
Under constant routine conditions in which exogenous factors are removed or fixed, only 10-20% of metabolites appear rhythmic.
“However, under constant routine conditions in which exogenous factors are removed or fixed, only 10–20% of metabolites appear rhythmic (5–7).”
From Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism (2018) · cites this paper as [5]
Up to 20% of detectable metabolites in human matrices such as plasma and saliva exhibit daily rhythms.
“In addition to these mouse studies, human metabolome analyses also reveal that up to 20% of detectable metabolites in matrices such as plasma and saliva exhibit daily rhythms (44)(45)(46).”
From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [44]
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“Recently, the constant routine protocol has been used to examine metabolites in saliva and plasma at different times of day to identify those that are under circadian control and are independent of sleep.(78,79) Remarkably, one study found that metabolites from blood taken every 2 h, which”
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“This ubiquity of circadian rhythms is reflected at the protein [6] and metabolite levels [7].”
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- Authors
- Dallmann, R., Viola, A. U., Tarokh, L., Cajochen, C., & Brown, S. A.
- Affiliations
- University of Zurich (CH)
- University of Basel (CH)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-01-31
- Volume
- 109
- Issue
- 7
- Pages
- 2625-2629
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3289302
- OpenAlex
- W2122927821
- Cited by
- 566
- References
- 40
- Citations by year
- 2026: 18 · 2025: 31 · 2024: 35 · 2023: 47 · 2022: 29 · 2021: 38 · 2020: 48 · 2019: 33 · 2018: 37 · 2017: 47 · 2016: 47 · 2015: 58 · 2014: 41 · 2013: 34 · 2012: 23
- FWCI
- 22.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- BORIS (University Library Bern) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation
- Alexander von Humboldt-Stiftung
- Velux Stiftung
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Hartmann Müller-Stiftung für Medizinische Forschung
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- circadian clock, plasma metabolites, saliva metabolites, circadian rhythm, fatty acids, amino acids, constant routine, sleep deprivation, sleep pressure
- MeSH terms
- Circadian Rhythm, Humans, Light, Saliva, Metabolome
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