Annals of Work Exposures and Health, 2023, 67, 694–705
Advance access publication 26 April 2023
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
*Author to whom correspondence should be addressed. Tel: + 0031 6 45362841; E-mail: email@example.com
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
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
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.
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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
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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