Effects of Nightshift Work on Blood Metabolites in Female Nurses and Paramedic Staff Worksheet

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Annals of Work Exposures and Health, 2023, 67, 694–705 https://doi.org/10.1093/annweh/wxad018 Advance access publication 26 April 2023 Original Article Daniella van de Langenberg1,2, Martijn E.T. Dollé2, Linda W.M. van Kerkhof2, Roel C.H. Vermeulen1, and Jelle J. Vlaanderen1,* IRAS, Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 2, 3584 CM, Utrecht, the Netherlands; RIVM, Rijksinstituut voor Volksgezondheid en Milieu (National Institute for Public Health and the Environment), Antonie van Leeuwenhoeklaan 9, 3721 MA, Bilthoven, the Netherlands 1 2 *Author to whom correspondence should be addressed. Tel: + 0031 6 45362841; E-mail: j.j.vlaanderen@uu.nl Abstract Nightshift work disturbs the circadian rhythm, which might contribute to the development of cardio-metabolic disorders. In this cross-sectional study, we aimed to gain insight into perturbations of disease relevant metabolic pathways due to nightshift work. We characterized the metabolic profiles of 237 female nurses and paramedic staff participating in the Klokwerk study using the Nightingale Health platform. We performed analyses on plasma levels of 225 metabolites, including cholesterol, triglycerides, fatty acids, and amino acids. Using both principal component- and univariate-regression, we compared metabolic profiles of nightshift workers to metabolic profiles from workers that did not work night shifts (defined as day workers). We also assessed whether differential effects were observed between recently started versus more experienced workers. Within the group of nightshift workers, we compared metabolic profiles measured right after a nightshift with metabolic profiles measured on a day when no nightshift work was conducted. We observed evidence for an impact of nightshift work on the presence of unfavorable fatty acid profiles in blood. Amongst the fatty acids, effects were most prominent for PUFA/FA ratios (consistently decreased) and SFA/FA ratios (consistently elevated). This pattern of less favorable fatty acid profiles was also observed in samples collected directly after a night shift. Amino acid levels (histidine, glutamine, isoleucine, and leucine) and lipoproteins (especially HDL-cholesterol, VLDL-cholesterol, and triglycerides) were elevated when comparing nightshift workers with day workers. Amino acid levels were decreased in the samples that were collected directly after working a nightshift (compared to levels in samples that were collected during a non-nightshift period). The observed effects were generally more pronounced in samples collected directly after the nightshift and among recently started compared to more experienced nightshift workers. Our finding of a suggested impact of shift work on impaired lipid metabolism is in line with evidence that links disruption of circadian rhythmicity to obesity and metabolic disorders. Keywords: blood metabolites; cardio-metabolic disorders; chronobiology; circadian rhythm; fatty acids; night work; occupational health; shift work What’s Important About This Paper? This study is the first to apply the Nightingale metabolomics platform to gain insight into the impact of night-shift work on perturbations in blood metabolites, relative to non-night-shift work. Further, the study, untangled night-shift work related effects on blood metabolites, demonstrating impaired lipid metabolism among night shift workers. These results support existing evidence that disruption of circadian rhythmicity by night-shift work is a risk factor for obesity and metabolic disorders. Received: July 25, 2022. Accepted: March 16, 2023. © The Author(s) 2023. Published by Oxford University Press on behalf of the British Occupational Hygiene Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/ by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Downloaded from https://academic.oup.com/annweh/article/67/6/694/7143613 by University of Illinois at Chicago user on 07 September 2023 Effects of Nightshift Work on Blood Metabolites in Female Nurses and Paramedic Staff: A Crosssectional Study Annals of Work Exposures and Health, 2023, Vol. 67, No. 6 Background Methods Study set-up and sample collection The study design of the Klokwerk study is described elsewhere (van de Langenberg et al., 2019, 2018). In brief, the study population consisted of 237 female nurses and paramedic staff between ages 18 and 65. To research effects of nightshift work on metabolic biomarkers we compared nightshift workers with participants who did not perform nightshift work in the last 5 years, defined as ‘day-workers’ (control subjects). Night-shift workers worked in a rotating shift-work schedule and organize their own schedules (self-schedule). We collected (nonfasting) blood samples during time-periods in which study participants did not conduct nightshift work (defined as a day session). During these day sessions, samples were ideally collected on days and times when participants were least disrupted by their rotating-shift working schedule: while working afternoon shifts (i.e. their working schedule did not affect their preferred time of waking up) and as long as possible after their last night shift (median of 9 days). A subset of the participants (n = 90) has been studied more extensively, with a more demanding study protocol. Within this subset, we aimed to collect blood samples twice per participant during day sessions (during two separate sessions). To analyse acute effects of nightshift work, within this subset, we collected one (non-fasting) blood sample in the morning immediately after a nightshift session for nightshift workers (n = 69), and compared with samples taken during day work, at the start of the shift. Biological sampling was conducted at the end of at least two consecutive day- or nightshifts. ‘Day work’ was defined as all work that does not cover the definition of a ‘night shift’. Besides traditional working hours during the day, day work also includes morning and afternoon shifts. We defined nightshift work as working at least one night shift every 6 weeks in a rotating schedule. We defined a night shift as having worked at least one hour between midnight and 06:00 AM. We performed additional analyses, for which nightshift workers were divided into experienced nightshift workers (started working night shifts over 5 years ago), and recently-started nightshift workers (less than 2 years ago). We approached potentially eligible participants via a screening questionnaire that was distributed among nurses in five selected hospitals in the Netherlands. All participants signed an informed consent. Inclusion of the participants took place between February 2015 and February 2017. To participate in the study, subjects had to agree to blood sampling, and fill out the questionnaires. We excluded current smokers and former smokers who quit smoking
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Journal Outline

Info About Article
a. Title
i. “Effects of Nightshift Work on Blood Metabolites in Female Nurses
and Paramedic Staff: A Crosssectional Study.”
b. Journal
i. British Journal of Occupational Hygiene Society.
c. First Author
i. Daniella van de Langenberg
d. Institution
i. Utrecht University
ii. Rijksinstituut voor Volksgezondheid en Milieu (National Institute for
Public Health and the Environment)
e. Funding Source
i. The Dutch Ministry of Social Affairs and Employment.
ii. The RIVM Strategic program.
iii. The Exposome Project for Health and Occupational Research
(EPHOR) which is funded by the European Union's Horizon 2020
research and innovation programme under grant agreement number
f. Conflict-Of-Interest
i. No, the article explicitly states that the authors had no conflicts of


a. Why the Study Was Performed

i. The study's primary purpose was to find out how working nights
affected the blood metabolic profiles of paramedic staff and female
nurses. The study aimed to learn more about how working nights
affects disease-relevant metabolic pathways. The study sought to
further knowledge about the potential health effects of working night
shifts, particularly about metabolic problems, by evaluating metabolic
b. What’s Already Known About the Topic
i. Prior studies have demonstrated that night shift work, can interfere
with circadian rhythms, resulting in irregular sleep patte...

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