Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism
Open accessAbstract
Significance: Shift workers, whose schedules are misaligned relative to their suprachiasmatic nuclei (SCN) circadian pacemaker, are at elevated risk of metabolic disorders. In a study of simulated day- versus night-shift work followed by a constant routine, we separated plasma-circulating metabolites according to whether their 24-h rhythms aligned with the central SCN pacemaker or instead reflected externally imposed behavioral schedules. We found that rhythms in many metabolites implicated in food metabolism dissociated from the SCN pacemaker rhythm, with the vast majority aligning with the preceding sleep/wake and feeding/fasting cycles. Our metabolomics study yields insight into the link between prolonged exposure to shift work and the spectrum of associated metabolic disorders by providing a window into peripheral oscillators and the biobehavioral factors that orchestrate them.
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Written from the paper’s full text.
TL;DR
In a controlled simulated shift-work study, most plasma metabolite rhythms after night-shift exposure tracked prior behavioral schedules rather than the central SCN pacemaker. The findings suggest that externally imposed sleep/wake and feeding/fasting cycles can drive peripheral metabolic rhythmicity and dissociate it from central circadian timing.
Key findings
- Central circadian markers—DLMO, plasma cortisol, and PER3 expression—showed only a ∼2 h delay after the simulated night-shift condition, indicating the SCN pacemaker was resistant to phase shifting.
- Of 132 targeted plasma metabolites, 65 showed significant 24-h rhythmicity during constant routine under either or both conditions; 62 of 132 showed profound timing changes after simulated night work.
- Among 27 metabolites rhythmic under both conditions, only 3—serotonin, taurine, and sarcosine—maintained approximately stable peak timing relative to central circadian markers; 24 shifted, often reversing by ∼12 h, and aligned with the preceding behavioral cycles.
- Pathway analyses found 9 significantly enriched pathways after the day-shift condition and 5 after the night-shift condition, including aminoacyl-tRNA biosynthesis, nitrogen metabolism, and arginine–proline metabolism in both.
Methods
- Between-groups in-laboratory study: healthy volunteers ages 22–34 y were assigned to 3 d of simulated night shift (n = 7) or simulated day shift (n = 7), followed by a 24-h constant routine.
- Blood samples were taken during constant routine at intervals of 1–3 h for targeted LC/MS metabolomics of 132 circulating metabolites from 5 classes, plus cortisol and PER3 assays; additional hourly samples were used for melatonin assays.
- Metabolite rhythms were assessed with cosinor analysis, corroborated by principal component analysis and pathway analyses.
Limitations
- The paper states that the 24-h constant routine was relatively short, the targeted metabolomics approach did not cover the entire metabolome, and the paradigm could not disentangle which external time cues—light/dark exposure, sleep/wakefulness, rest/activity, and/or feeding/fasting—drove the behavior-driven rhythms.
- The paper also states that the study involved acute simulated night-shift work in healthy non–shift-working volunteers, so results do not readily generalize to real-world shift-work settings, and the sample of 14 subjects was relatively small.
- Evident from the text: the between-groups design and 3-d exposure limit causal inference about longer-term adaptation and chronic metabolic outcomes.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
0 of 13 cited sources checked · 0 supported · 0 flagged
- Findingown data
Of the 27 metabolites rhythmic under both conditions, only three (serotonin, taurine, and sarcosine) maintained approximately the same peak time following both schedules.
“Only three of these metabolites maintained approximately the same peak time following both the simulated day-shift and night-shift schedules (as did the traditional circadian markers, DLMO and cortisol peak): serotonin, taurine, and sarcosine (Fig. 2, Left).”
Quote in the paperSubstantial claim - Findingreasoning
The night-shift condition successfully produced misalignment between behavioral rhythms shifted by 12 h and the relatively unyielding rhythm of the central SCN pacemaker.
“Thus, the night-shift condition successfully produced misalignment between behavioral rhythms (light/dark exposure; sleep/wakefulness; rest/activity; feeding/fasting), which were shifted by 12 h under the simulated night-shift condition, and the relatively unyielding rhythm of the central SCN pacemaker.”
Quote in the paperSubstantial claim - Findingown data
Nearly half of the analyzed metabolites (65 of 132) showed significant 24-h rhythmicity during constant routine under either or both conditions.
“Nearly half of the metabolites analyzed (i.e., 65 of 132) showed significant 24-h rhythmicity during the constant routine under either or both conditions.”
Quote in the paperSubstantial claim - Findingown data
A delay of approximately 2 h was observed after the night-shift condition regardless of which rhythm marker was used.
“A delay of ∼2 h was observed after the night-shift condition, regardless of which rhythm marker was used”
Quote in the paperSubstantial claim - Findingown data
During constant routine after 3 d of simulated shift work, DLMO, plasma cortisol rhythm, and PER3 expression rhythm showed relatively little phase difference between day-shift and night-shift conditions.
“During the constant routine after 3 d of simulated shift work, the dim light melatonin onset (DLMO) and the 24-h rhythm of plasma cortisol (traditional markers of the central SCN pacemaker) as well as the 24-h rhythm in clock gene PER3 expression all showed relatively little phase difference between the day-shift and night-shift conditions (SI Appendix, Figs. S2–S4).”
Quote in the paperSubstantial claim
- Findingown data
Principal component analysis corroborated the subdivision according to observed rhythms, yielding three distinct clusters of metabolites.
“The subdivision according to the observed rhythms following the day- and night-shift schedules as captured in Fig. 1 was corroborated by principal component analysis, which yielded three distinct clusters of metabolites (SI Appendix, Table S2).”
Quote in the paperNot a substantial claim - Interpretationcitation
Exogenous behavioral time cues associated with externally imposed schedules have the capacity to drive endogenous rhythmicity in metabolism, likely by impacting peripheral oscillators and dissociating them from the rhythm of the central SCN pacemaker.
“Exogenous, behavioral time cues associated with externally imposed schedules thus have the capacity to drive endogenous rhythmicity in metabolism, likely by impacting on peripheral oscillators (17, 18) and dissociating them from the rhythm of the central SCN pacemaker.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [17] Damiola F 2000 Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus Genes Dev 14 2950 2961 11114885 PMC317100 source
Not checked in the free run.
- cites [18] Wehrens SMT 2017 Meal timing regulates the human circadian system Curr Biol 27 1768 1775.e3 28578930 PMC5483233 source
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- Premisecitation
Desynchronization of the circadian timing system from behavioral rhythms over time results in metabolic disorders including obesity, metabolic syndrome, and type 2 diabetes.
“Desynchronization of this circadian timing system from externally imposed behavioral rhythms (light/dark exposure; sleep/wakefulness; rest/activity; feeding/fasting)—such as occurs in shift workers—over time results in a number of metabolic disorders including obesity, metabolic syndrome, and type 2 diabetes (2).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [2] Kecklund G Axelsson J 2016 Health consequences of shift work and insufficient sleep BMJ 355 i5210 27803010 source
Not checked in the free run.
- Interpretationown data
The persistence of altered metabolite rhythms under constant routine in the absence of externally imposed rhythms provides strong evidence that most observed metabolite rhythms were driven by behavioral time cues during the preceding simulated shift schedules.
“Importantly, the altered rhythms persisted under constant routine conditions in the absence of any externally imposed rhythms. This provides strong evidence that most of the metabolite rhythms observed were driven by behavioral time cues—from the light/dark exposure, sleep/wakefulness, rest/activity, and/or feeding/fasting cycles—during”
Quote in the paperSubstantial claim - Interpretationown data
The alignment of the SM C20:2 rhythm with zeitgeber time despite the absence of behavioral cycles under constant routine provides substantial evidence that observed rhythms in this metabolite and others like it were driven by behavioral rhythms in the preceding shift days and subsequently retained.
“This was observed despite the fact that these behavioral cycles were no longer present under the constant routine conditions in which these metabolites were measured, providing substantial evidence that the observed rhythms in this metabolite (and others like it) were driven by behavioral rhythms in the preceding shift days and were subsequently retained.”
Quote in the paperSubstantial claim - Interpretationown data
The observed 24-h rhythms in the other 62 metabolites provide a window on peripheral clock function in the liver, pancreas, and digestive tract.
“The observed 24-h rhythms in the other 62 metabolites, most of which are bioactive lipids, amino acids, acylcarnitines, and other compounds implicated in metabolic processes and energy metabolism, provide a window on peripheral clock function in the liver, pancreas, and digestive tract.”
Quote in the paperSubstantial claim- Rests on an assumption: Plasma-circulating metabolite rhythms can serve as biomarkers of peripheral clock disturbances.
- Premisecitation
The central circadian clock in the SCN synchronizes peripheral clocks in liver, gut, pancreas, and adipose tissue via neural and hormonal pathways.
“In normal physiology, the central circadian clock, located in the hypothalamic suprachiasmatic nuclei (SCN), synchronizes the timing of peripheral clocks in the liver, gut, pancreas, and adipose tissue via multiple neural and hormonal pathways (1).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] Reppert SM Weaver DR 2002 Coordination of circadian timing in mammals Nature 418 935 941 12198538 source
Not checked in the free run.
- Interpretationreasoning
The observed rhythms in circulating metabolites and the metabolic pathways affected appear to reflect metabolic processes in the liver, pancreas, and digestive tract.
“As such, the observed rhythms in circulating metabolites and the metabolic pathways affected appear to reflect metabolic processes in the liver, pancreas, and digestive tract.”
Quote in the paperNot a substantial claim- Rests on an assumption: Plasma-circulating metabolite rhythms can serve as biomarkers of peripheral clock disturbances.
- Premisecitation
Previous studies in simulated and real-world shift work show that rhythms of circadian markers are resistant to phase shifting, indicating the endogenous SCN rhythm is slow to adapt to shift work schedules.
“Previous studies in both simulated (10, 11) and real-world (12, 13) shift work have shown that the rhythms of these circadian markers are resistant to phase shifting, indicating that the endogenous SCN rhythm is slow to adapt to shift work schedules.”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [10] Lee C Smith MR Eastman CI 2006 A compromise phase position for permanent night shift workers: Circadian phase after two night shifts with scheduled sleep and light/dark exposure Chronobiol Int 23 859 875 16887753 source
Not checked in the free run.
- cites [11] James FO Cermakian N Boivin DB 2007 Circadian rhythms of melatonin, cortisol, and clock gene expression during simulated night shift work Sleep 30 1427 1436 18041477 PMC2082093 source
Not checked in the free run.
- cites [12] Hansen JH Geving IH Reinertsen RE 2010 Adaptation rate of 6-sulfatoxymelatonin and cognitive performance in offshore fleet shift workers: A field study Int Arch Occup Environ Health 83 607 615 20499083 source
Not checked in the free run.
- cites [13] Boivin DB Boudreau P James FO Kin NM 2012 Photic resetting in night-shift work: Impact on nurses’ sleep Chronobiol Int 29 619 628 22621359 source
Not checked in the free run.
- Premisecitation
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).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [5] Dallmann R Viola AU Tarokh L Cajochen C Brown SA 2012 The human circadian metabolome Proc Natl Acad Sci USA 109 2625 2629 22308371 PMC3289302 source
Not checked in the free run.
- cites [6] Kasukawa T 2012 Human blood metabolite timetable indicates internal body time Proc Natl Acad Sci USA 109 15036 15041 22927403 PMC3443163 source
Not checked in the free run.
- cites [7] Chua EC 2013 Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans Proc Natl Acad Sci USA 110 14468 14473 23946426 PMC3761633 source
Not checked in the free run.
- May combine two claims. 8
- The quote only partly states this claim. 1
- Classified as probably not a substantial claim. 1
May combine two claims.
Findingown dataAmong rhythmic metabolites, 27 were rhythmic under both schedules, 19 lost rhythmicity after night-shift, and 19 emerged after night-shift.
“Of these, a group of 27 metabolites showed rhythmicity following both the simulated day-shift and night-shift schedules. A group of 19 metabolites lost their rhythmicity under constant routine following the night-shift schedule. For another group of 19 metabolites, no significant rhythmicity was observed following the day-shift schedule, but rhythmicity emerged under constant routine following the”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn the current study, many plasma metabolites (62 of 132) showed profound changes in the timing of their rhythms following simulated night work, whereas traditional SCN clock markers remained relatively stable after 3 d of simulated shift work.
“We found that, whereas traditional markers of the circadian clock in the SCN (melatonin, cortisol, PER3 expression) remained relatively stable after 3 d of simulated shift work, many of the plasma metabolites (62 of 132) showed profound changes in the timing of their rhythms following simulated night work (Fig. 1; SI Appendix, Table S1).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataUnder constant routine following simulated night-shift, 24 metabolites significantly shifted-and in most cases essentially reversed (shifted by 12 h)-their rhythms.
“By contrast, under constant routine following the simulated night-shift schedule, 24 metabolites significantly shifted—and in most cases essentially reversed (i.e., shifted by 12 h)—their rhythms.”
Quote in the paperSubstantial claimMay combine two claims. The quote only partly states this claim.
Findingown dataUnder the day-shift condition nine pathways were significantly enriched, and under the night-shift condition five pathways were significantly enriched.
“Under the day-shift condition, nine pathways were significantly enriched (SI Appendix, Table S3), including aminoacyl-tRNA biosynthesis, nitrogen metabolism, arginine–proline metabolism, and d-glutamine–glutamate metabolism—as well as alanine–asparate–glutamate metabolism, cyanoamino acid metabolism, d-arginine and d-ornithine metabolism, glutathione metabolism, and glycine–serine–threonine”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationMelatonin and cortisol rhythms are driven directly by SCN timing and are reliable markers of the phase of the central SCN clock.
“The rhythmic production of the hormones melatonin and cortisol is driven directly by SCN timing; these hormones are therefore considered reliable markers of the phase of the central SCN clock (8).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] Arendt J Skene DJ 2005 Melatonin as a chronobiotic Sleep Med Rev 9 25 39 15649736 source
Not checked in the free run.
May combine two claims.
Interpretationown dataThe SCN pacemaker was resistant to phase shifting by the behaviorally imposed schedule, and adaptation of the endogenous SCN timing system to the night-shift schedule was limited.
“This indicates that the SCN pacemaker was resistant to phase shifting by the behaviorally imposed schedule, as expected, and that adaptation of the endogenous SCN timing system to the night-shift schedule was limited.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductcitationThe targeted metabolomics approach used is quantitative and reliable and can be more readily confirmed and validated in other laboratories compared with whole-metabolome analyses.
“While our targeted approach is restrictive in that regard, it is quantitative and reliable (39) and, compared with whole-metabolome analyses, can be more readily confirmed and validated in other laboratories.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [39] Siskos AP 2017 Interlaboratory reproducibility of a targeted metabolomics platform for analysis of human serum and plasma Anal Chem 89 656 665 27959516 PMC6317696 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe 24-h duration of the constant routine protocol was relatively short, which is a limitation of the study.
“The 24-h duration of our constant routine protocol was relatively short, which is a limitation of the study.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningThe study involved acute exposure to simulated night-shift work in healthy non-shift-working volunteers inside the laboratory, and the results therefore do not readily generalize to real-world shift-work settings.
“Although our study involved acute exposure to simulated night-shift work in healthy non–shift-working volunteers inside the laboratory, and the results therefore do not readily generalize to real-world shift-work settings”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The mechanisms linking shift work with an increased risk of type 2 diabetes are not well understood.
“The mechanisms linking shift work with an increased risk of type 2 diabetes are not well understood.”
The paper relies on this without support.
A reliable tool to separate circadian- and behavior-driven rhythms in metabolism to test the misalignment hypothesis has been lacking.
“However, a reliable tool to separate circadian- and behavior-driven rhythms in metabolism to test this hypothesis has been lacking.”
The paper relies on this without support.
It remains unknown whether oscillations in metabolites that remain rhythmic under constant routine are driven by the central SCN pacemaker or reflect peripheral oscillators continuing to cycle without externally imposed behavioral time cues.
“It remains unknown whether the oscillations seen in metabolites that remain rhythmic under constant routine conditions are driven by the central SCN pacemaker or whether they are reflections of peripheral oscillators that continue to cycle in the absence of externally imposed behavioral time cues that were initially driving them.”
The paper relies on this without support.
Plasma-circulating metabolite rhythms can serve as biomarkers of peripheral clock disturbances.
“Investigating rhythms in circulating metabolites as biomarkers of peripheral clock disturbances may enable this, thereby offering an important step forward.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Shift workers or people who sleep poorly are more likely to develop obesity and T2DM due to circadian clock disruption.
“Shift workers or people who sleep poorly are more likely to develop obesity and T2DM due to circadian clock disruption 31, 32, 33, 34, 35, 36, 37.”
From The Circadian Syndrome: is the Metabolic Syndrome and much more! (2019) · cites this paper as [31]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Arginine-ornithine pathway described as both absent and enriched after night shift
MinorThe day-shift results say the d-arginine and d-ornithine metabolism pathway was not significantly enriched under night shift, but the night-shift results list d-arginine-ornithine metabolism among the significantly enriched pathways.
“d-arginine and d-ornithine metabolism, glutathione metabolism, and glycine–serine–threonine metabolism, which were not significantly enriched under the night-shift condition.”
“Under the night-shift condition, five pathways were significantly enriched (SI Appendix, Table S4), including aminoacyl-tRNA biosynthesis, nitrogen metabolism, arginine–proline metabolism, and d-arginine–ornithine metabolism”
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Young, M. E., & McGinnis, G. R. (2016) · Nature and Science of Sleep · doi:10.2147/nss.s78946 · Cited by 80 · see citing works
Tryptophan Metabolism via the Kynurenine Pathway in Experimental Chronic Renal Failure
Pawlak, D., Tankiewicz‐Kwedlo, A., Myśliwiec, P. A., et al. (2002) · The Nephron journals/Nephron journals · doi:10.1159/000049069 · Cited by 77 · see citing works
Twenty‐four‐hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes
Isherwood, C., van der Veen, D. R., Johnston, J. D., & Skene, D. J. (2017) · The FASEB Journal · doi:10.1096/fj.201700323r · Cited by 67 · see citing works
Self-citationShort Sleep Duration Increases the Risk of Chronic Kidney Disease in Shift Workers
Sasaki, S., Yoshioka, E., Saijo, Y., Kita, T., Tamakoshi, A., & Kishi, R. (2014) · Journal of Occupational and Environmental Medicine · doi:10.1097/jom.0000000000000322 · Cited by 47 · see citing works
Association Between Shiftwork and Glomerular Filtration Rate in Police Officers
Charles, L. E., Gu, J. K., Fekedulegn, D. B., Andrew, M. E., Violanti, J. M., & Burchfiel, C. M. (2013) · Journal of Occupational and Environmental Medicine · doi:10.1097/jom.0b013e3182a299c9 · Cited by 33 · see citing works
Hansen, J. H., Geving, I. H., & Reinertsen, R. E. (2010) · International Archives of Occupational and Environmental Health · doi:10.1007/s00420-010-0547-x · Cited by 29 · see citing works
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The Circadian Syndrome: is the Metabolic Syndrome and much more!
Zimmet, P., Alberti, K. G. M. M., Stern, N., Bilu, C., El‐Osta, A., Einat, H., & Kronfeld‐Schor, N. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12924 · Cited by 387 · see citing works
Food as a circadian time cue - evidence from human studies
Lewis, P., Oster, H., Korf, H. W., Foster, R. G., & Erren, T. C. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0318-z · Cited by 207 · see citing works
Melatonin effects on glucose metabolism: time to unlock the controversy
Garaulet, M., Qian, J., Florez, J. C., Arendt, J., Saxena, R., & Scheer, F. A. J. L. (2020) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2019.11.011 · Cited by 193 · see citing works
Daytime eating prevents internal circadian misalignment and glucose intolerance in night work
Chellappa, S. L., Qian, J., Vujovic, N., Morris, C. J., Nedeltcheva, A., Nguyen, H., Rahman, N., Heng, S. W., Kelly, L., Kerlin-Monteiro, K., et al. (2021) · Science Advances · doi:10.1126/sciadv.abg9910 · Cited by 135 · see citing works
Connecting insufficient sleep and insomnia with metabolic dysfunction
Duan, D., Kim, L. J., Jun, J. C., & Polotsky, V. Y. (2023) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14926 · Cited by 110 · see citing works
Tabarin, A., Assié, G., Barat, P., Bonnet, F., Bonneville, J. F., Borson-Chazot, F., Bouligand, J., Boulin, A., Brue, T., Caron, P., et al. (2022) · Annales d Endocrinologie · doi:10.1016/j.ando.2022.02.001 · Cited by 59 · see citing works
Night shift schedule alters endogenous regulation of circulating cytokines
Liu, P. Y., Irwin, M. R., Krueger, J. M., Gaddameedhi, S., & Van Dongen, H. P. A. (2021) · Neurobiology of Sleep and Circadian Rhythms · doi:10.1016/j.nbscr.2021.100063 · Cited by 33 · see citing works
Self-citationThe real-world association between digital markers of circadian disruption and mental health risks
Lee, M. P., Kim, D. W., Fang, Y., Kim, R., Bohnert, A. S. B., Sen, S., & Forger, D. B. (2024) · npj Digital Medicine · doi:10.1038/s41746-024-01348-6 · Cited by 29 · see citing works
- Authors
- Skene, D. J., Skornyakov, E., Chowdhury, N. R., Gajula, R. P., Middleton, B., Satterfield, B. C., Porter, K. I., Van Dongen, H. P. A., & Gaddameedhi, S.
- Affiliations
- University of Surrey (GB)
- Eastern Washington University (US)
- Washington State University Spokane (US)
- University of Arizona (US)
- Sleep and Performance Research Center, Washington State University, Spokane, WA 99210;
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2018-07-10
- Volume
- 115
- Issue
- 30
- Pages
- 7825-7830
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6065025
- OpenAlex
- W2814914586
- Semantic Scholar
- 9327a903c17e03fe52c3d0567214f68ef650d1c3
- Cited by
- 176
- References
- 46
- Citations by year
- 2026: 16 · 2025: 16 · 2024: 25 · 2023: 25 · 2022: 23 · 2021: 21 · 2020: 28 · 2019: 15 · 2018: 7
- FWCI
- 9.99
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-08-30)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Funders
- DOD | United States Army | MEDCOM | Congressionally Directed Medical Research Programs (W81XWH-16-1-0319)
- HHS | NIH | National Institute of Environmental Health Sciences (R00ES022640)
- RCUK | Biotechnology and Biological Sciences Research Council (BB/I019405/1)
- EC | Seventh Framework Programme (FP7-HEALTH-2011)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- circadian rhythm, shift work, suprachiasmatic nucleus, peripheral oscillators, constant routine, sleep-wake cycle, feeding-fasting cycle, food metabolism, metabolic disorders, plasma metabolites, circadian misalignment
- MeSH terms
- Adult, Biological Clocks, Circadian Rhythm, Fasting, Female, Gene Expression Regulation, Humans, Hydrocortisone, Male, Melatonin, Period Circadian Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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