Evidence links night shift work to circadian rhythm disruption, causing hormonal and metabolic alterations, as well as increased risk for cardiovascular disease (CVD). This study investigates whether night shift work affects blood glucose variability and dysregulation, potentially driven by circadian misalignment. It also examines whether such disruptions elevate inflammatory markers involved in atherosclerosis and contribute to the exacerbation of CVD risk markers.

The study includes 60 participants: rotating night shift workers (day, evening, and night shifts) and day workers (controls) at a pharmaceutical plant. We will assess the effects of night shift work on metabolic and cardiovascular health over three phases: an initial 6-week observational period (phase I), baseline registration of CVD risk factors (phase II), and follow-up assessment of CVD risk factors at 2 years (phase III). Phase I registrations include working hours derived from payroll data, sleep metrics by OURA ring (actigraphy, plethysmography and temperature), continuous assessments of blood glucose using continuous glucose monitor, self-reported food diary and measurements of circadian rhythm markers (monocyte mRNA expression). In phases II and III, blood CVD risk factors such as markers of inflammation, lipids, glycosylated haemoglobin, D-dimer, clinical examination of blood pressure, resting heart rate, arterial stiffness by the means of carotid to femoral pulse wave velocity, carotid intima-media thickness and maximal oxygen uptake (V̇O2max) are measured. To this end, a comprehensive set of methods will be used in a prospective manner to provide new knowledge on shift work-induced glucose regulation and CVD risk factors.

All participants provided written informed consent prior to participating in the study, which will adhere to the principles outlined in the Declaration of Helsinki. Ethical approval has been granted by the Norwegian Regional Committee for Medical Research Ethics South-East B (reference # 745702). Dissemination plans include academic and public publications, as well as collaborations with national and regional policy-makers.

Effective countermeasures against the adverse cardiovascular effects of circadian misalignment, such as effects experienced due to night work or jet lag, remain to be established in humans. Here, we aim to test whether eating only during daytime can mitigate such adverse effects vs. eating during the night and day (typical for night shift workers) under simulated night work (secondary analysis of NCT02291952). This single-blind, parallel-arm trial randomized 20 healthy participants (non-shift workers) to simulated night work with meals consumed during night and day (Nighttime Meal Control Group) or only during daytime (Daytime Meal Intervention Group). The primary outcomes were pNN50 (percentage consecutive heartbeat intervals >50 ms), RMSSD (root mean square of successive heartbeat differences), and LF/HF (low/high cardiac frequency). The secondary outcome was blood concentrations of prothrombotic factor plasminogen activator inhibitor-1 (PAI-1). These measures were assessed under Constant Routine conditions, before (baseline) and after (postmisalignment) simulated night work. The meal timing intervention significantly modified the impact of simulated night work on cardiac vagal modulation and PAI-1 (pFDR = 0.001). In the Control Group, the postmisalignment Constant Routine showed a decrease in pNN50 by 25.7% (pFDR = 0.008) and RMMSD by 14.3% (pFDR = 0.02), and an increase in LF/HF by 5.5% (pFDR = 0.04) and PAI-1 by 23.9% (pFDR = 0.04), vs. the baseline Constant Routine. In the Intervention Group, there were no significant changes in these outcomes. For exploratory outcomes, the intervention significantly modified the impact of simulated night work on blood pressure (P < 0.05), with no significant change in the Control Group, and a significant reduction by 6-8% (P < 0.01) in the Intervention Group; without significant effects for heart rate or cortisol. These findings indicate that daytime eating, despite mistimed sleep, may mitigate changes in cardiovascular risk factors and offer translational evidence for developing a behavioral strategy to help minimize the adverse changes in cardiovascular risk factors in individuals exposed to circadian misalignment, such as shift workers.

Photobiological hydrogen production offers a sustainable route to clean energy by harnessing solar energy through photosynthetic microorganisms. The pioneering sulfur-deprivation technique developed by Melis and colleagues in the green alga Chlamydomonas reinhardtii successfully enabled sustained hydrogen production by downregulating photosystem II (PSII) activity to reduce oxygen evolution, creating anaerobic conditions necessary for hydrogenase activity. Inspired by this approach, we present the project of the European consortium PhotoSynH2, which builds on these biological insights and employs synthetic biology to replicate and enhance this strategy in cyanobacteria, specifically, Synechocystis sp. PCC 6803. By genetically engineering precise downregulation of PSII, we aim to reduce oxygen evolution without the unintended effects associated with nutrient deprivation, enabling efficient hydrogen production. Additionally, re-engineering endogenous respiration to continuously replenish glycogen consumed during respiration allows matching oxygen production with consumption, maintaining anaerobic conditions conducive to hydrogen production. This review discusses how focusing on molecular-level processes and leveraging advanced genetic tools can lead to a new methodology that potentially offers improved results over traditional approaches. By redirecting electron flow and optimizing redox pathways, we seek to enhance hydrogen production efficiency in cyanobacteria. Our approach demonstrates how harnessing photosynthesis through synthetic biology can contribute to scalable and sustainable hydrogen production, addressing the growing demand for renewable energy and advancing toward a carbon-neutral future.

To determine the association of irregular dietary habits with HbA1c and body mass index (BMI) in people with diabetes.

We included 4,421 people with diabetes aged 20-74 years (type 1 diabetes (T1D), 19.1%) who answered a questionnaire at mealtime. Adjusted least square means in HbA1c and BMI in patients with irregular dietary habits: "irregular mealtimes (irregular)," "skipping breakfast (SB)," and "late dinner (LD)" were compared to those with "regular dietary habits (regular)." Multivariable logistic regression analyses were performed to examine the association of irregular dietary habits with HbA1c ≥ 7% and BMI ≥25 kg/m2.

HbA1c was significantly higher for "irregular" in both sexes and for "LD" in women than those of "regular" in people with T1D. HbA1c was significantly higher for "LD," and BMI was higher for almost all irregular dietary habits than those of "regular" in people with type 2 diabetes (T2D). Odds ratios (ORs) for HbA1c ≥7% were 3.20 (95% confidence interval (CI), 1.30-7.89) for T1D women with "irregular" and 1.73 (1.20-2.49) and 2.20 (1.14-3.65) for T2D men and women with "LD," respectively. ORs for BMI ≥25 kg/m2 were 1.60 (95% CI, 1.15-2.22) for T2D men with "irregular" and 1.43 (1.02-2.01) and 2.11 (1.21-3.65) for T2D women and men with "LD," respectively.

Irregular mealtimes are associated with poor glycemic control in T1D women and are associated with obesity in T2D men. Furthermore, a late dinner was associated with high HbA1c levels and BMI in people with T2D.

Night-shift work causes circadian misalignment and impairs glucose metabolism. We hypothesise that food intake during night shifts may contribute to this phenomenon.

This open-label, multi-arm, single-site, parallel-group controlled trial involved a 6 day stay at the University of South Australia's sleep laboratory (Adelaide, SA, Australia). Healthy, non-shift-working adults without obesity (N=55; age 24.5 ± 4.8 years; BMI 24.8 ± 2.8 kg/m2) were assigned to the next available run date and cluster randomised (1:1:1) to fasting-at-night (N=20), snack-at-night (N=17), or meal-at-night (N=18) conditions. One participant withdrew from each group, prior to starting the study. Due to study design, neither participants nor people collecting their measurements could be blinded. Statistical and laboratory staff were concealed to study allocation. Participants were fed at calculated energy balance, with the macronutrient composition of meals being similar across conditions. The primary outcomes were a linear mixed-effects model of glucose, insulin and NEFA AUC in response to a 75 g OGTT that was conducted prior to and after 4 consecutive nights of shift work plus 1 night of recovery sleep. Insulin sensitivity, insulinogenic and disposition indexes were also calculated.

Night-shift work impaired insulin sensitivity, as measured by insulin AUC (p=0.035) and the insulin sensitivity index (p=0.016) across all conditions. Insulin secretion, as measured by the insulinogenic index, was increased in the fasting-at-night condition only (p=0.030), resulting in a day×condition interaction in glucose AUC (p<0.001) such that glucose tolerance was impaired in the meal-at night (+2.00 [95% CI 1.45, 2.56], p<0.001) and snack at-night (+0.96 [0.36, 1.56], p=0.022) conditions vs the fasting-at-night (+0.34 [-0.21, 0.89]) condition. A day×condition interaction was also observed in NEFA AUC (p<0.001), being higher in the meal-at-night (+0.07 [0.03, 0.10]. p=0.001) and snack-at-night (0.01 [-0.03, 0.05], p=0.045) conditions vs the fasting-at-night condition (-0.02 [-0.06, 0.01]). No adverse events occurred.

The timing of food intake has a critical effect on glucose metabolism during simulated night-shift work, which was readily amendable to a meal re-timing intervention.

Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12616001556437 FUNDING: This work was funded by the National Health and Medical Research Council (NHMRC), APP1099077.

Over the past decades, the global prevalence of Type 2 diabetes mellitus (T2D) and impaired glucose tolerance (IGT) has been increasing at an epidemic rate, yet the exact cause remains unknown. It is widely accepted that glucose metabolism can be impaired by circadian rhythms and sleep disturbances. Concurrently, exposures to light at night have been closely linked to circadian and sleep disturbances. However, there is no direct experiment on primates to demonstrate the precise extent of how serious light pollution impairs glucose metabolism, whether people will eventually become accustomed to this environment, and whether the pollution has synergistic impairing effects with aging and weight on glucose metabolism. To quantitatively address these questions, 137 cynomolgus were exposed to three distinct nocturnal light intensities for consecutive 10 months. Monthly glucose metabolism assessments were conducted. Data pertaining to the mortality rate of preexisting diabetes, incidence of light-induced diabetes and IGT, and alterations in insulin secretion were collected and analyzed. The results show that nocturnal light (1) caused premature deaths in individuals with preexisting diabetes; (2) intensity-dependently induced diabetes and IGT in previous healthy monkeys; (3) intensity-dependently reduced melatonin secretion; (4) had a synergistic impairing effect on glucose metabolism with aging and weight; and (5) although monkeys would eventually adapt to the environment, the disrupted glucose metabolism would not fully recover in most individuals. In conclusion, nocturnal light is associated with the global high prevalence of T2D and IGT. The harmful effects of light pollution on glucose metabolism are synergistic with age and weight.

Evidence is increasingly suggesting that shift work is a risk factor for cardiometabolic disease. However, the causal relationship between shift work and cardiometabolic disease is not yet fully understood. In this study, we employed two-sample Mendelian randomization (MR) to investigate the causal relationship between shift work and the risk of cardiometabolic outcomes.

Genome-wide association study (GWAS) statistics for shift work were obtained from the UK Biobank. Mendelian randomization analyses were conducted to explore the causal effects of shift work on cardiometabolic outcomes, using single-nucleotide polymorphisms (SNPs) as instrumental variables. The results suggested a causal effect between shift work and body mass index, body fat percentage, triglycerides, high-density lipoprotein, type 2 diabetes, hypertension, and cardiorespiratory fitness. After correcting for multiple tests, only body mass index and high-density lipoprotein showed significant associations. No causal effects were found between shift work and overweight, obesity, total cholesterol, low-density lipoprotein, fasting glucose, 2-h glucose, fasting insulin, coronary artery disease, myocardial infarction, heart failure, atrial fibrillation, or ischemic stroke.

This MR study provides genetic evidence for a suggestive causal link between shift work and certain cardiometabolic outcomes. Our research may have the significance of providing insight into public hygiene to improve the understanding of shift work and cardiometabolic disease risk. Further experimental studies are needed to confirm our findings.

A growing body of evidence has placed an increasing emphasis on how sleep affects health. Not only does insufficient sleep make one subjectively feel worse, but is associated with chronic diseases that are considered epidemics in industrialized nations. This is partly caused by the growing need for prolonged work and social schedules, exemplified by shift work, late-night weekends, and early morning work/school start times (social jetlag). Here, we consider fundamental relationships between the circadian clock and biologic processes and discuss how common practices, such as shift work and social jetlag, contribute to sleep disruption, circadian misalignment, and adverse health outcomes.

Data on the relationship between sleep architecture and diabetes are limited. However, some evidence suggests that slow-wave sleep (SWS) plays a crucial role in maintaining normal glucose homeostasis and influences insulin secretion capacity. Diabetes is often associated with reduced SWS, even in the absence of sleep-disordered breathing. Notably, selective suppression of SWS-without reducing total sleep time-can lead to significant increases in insulin resistance, decreased glucose tolerance, and a higher risk of diabetes. Given the growing interest in non-pharmacological lifestyle interventions, such as modifying sleep architecture, it is important to understand how sleep patterns differ in individuals with diabetes and whether these alterations impact diabetes risk and glycemic control. This review aims to provide a concise overview of the current findings on sleep architecture changes in people with diabetes.

Recent studies have shown that both metabolic syndrome and circadian rhythm syndrome are firmly associated with the occurrence of cardiovascular disease (CVD), with insulin resistance playing a significant role. The estimated glucose disposal rate (eGDR) is considered to be a reliable surrogate marker for insulin resistance. However, the relationship between eGDR and CVD under different metabolic and circadian rhythm states has not been thoroughly studied, and large-scale prospective cohort studies are needed to clarify this relationship.

This study is based on the China Health and Retirement Longitudinal Study (CHARLS), recruiting individuals aged 45 and above with complete eGDR data. The eGDR was calculated by the formula: eGDR(mg/kg/min) = 21.158 - (0.09 × WC) - (3.407 × hypertension) - (0.551 × HbA1c) [WC (cm), hypertension (yes = 1/no = 0), and HbA1c (%)] (Zabala et al. in Cardiovasc Diabetol 20(1):202; 2021).Participants were divided into four subgroups based on the quartiles (Q) of eGDR.The cumulative incidence rates and hazard ratios (HR) with 95% confidence intervals (CI) were calculated, with the lowest eGDR quartile (representing the highest degree of insulin resistance) as the reference. Participants were further divided into subgroups based on the diagnosis of Metabolic syndrome (MetS) or circadian syndrome (CircS) to explore the relationship between eGDR and CVD under different metabolic and circadian rhythm conditions. The dose-response relationship between eGDR and CVD incidence was investigated using a restricted cubic spline (RCS) based on a Cox regression model. Receiver operating characteristic (ROC) curves were generated to assess the predictive value of eGDR for CVD incidence. A clinical decision curve analysis (DCA) was also conducted to assess the clinical utility of the basic model.

6507 participants were included, with a median age of 58 years [52 years, 64 years], and 55% were female. Over a median follow-up duration of 87 months, 679 first-episode CVD events were recorded, including heart disease and stroke. The RCS curves demonstrated a significant dose-response relationship between eGDR and the incidence of first-presentation CVD in different metabolic and circadian rhythm subgroups (all P-values < 0.001, non-linearity P > 0.05). eGDR exhibited a significant linear relationship with all outcomes (non-linearity P < 0.05). The Kaplan-Meier cumulative incidence curves showed that as eGDR levels increased, the cumulative incidence rates of first CVD, heart disease, and stroke gradually decreased from Q1 to Q4 groups. Significant differences were observed across all metabolic and circadian rhythm subgroups (log-rank test P < 0.001). Through the Cox proportional hazards model, we confirmed a significant association between baseline eGDR levels and first-onset CVD, heart disease, and stroke. Subgroup analyses indicated that the predictive ability of eGDR for CVD risk varied across different Body mass index (BMI) (P for interaction = 0.025) and age (P for interaction = 0.045) subgroups. Mediation analysis revealed that CircS partially mediated this association. Furthermore, time-dependent ROC curves demonstrated the potential of eGDR as a predictor of CVD risk, revealing possible differences in the model's application across different cardiovascular conditions.

eGDR is an independent predictor of CVD risk, with lower eGDR levels being closely associated with a higher risk of CVD (including heart disease and stroke). In populations with MetS or CircS, the association between lower eGDR levels and increased risk is more pronounced.

Due to work commitments, shiftworkers often obtain inadequate sleep, consequently experiencing negative health, wellbeing, and safety outcomes. Given shiftworkers may have limited control over their work commitments, lifestyle and environmental factors within their control may present an intervention opportunity. However, such interventions require tailoring to ensure applicability for this sleep-vulnerable population.

A randomised waitlist control pilot trial investigated the effectiveness of mobile health application Sleepfit, which delivered a tailored sleep health intervention aimed at improving sleep health and sleep hygiene outcomes amongst paramedic shiftworkers. Outcome measures of self-reported sleep health (sleep need, duration, and quality, fatigue, Insomnia Severity Index, Fatigue Severity Scale, and Epworth Sleepiness Scale scores) and sleep hygiene (Sleep Hygiene Index score) were collected at baseline, post-intervention, and 3-month follow-up.

Fifty-eight paramedics (aged 33.4 ± 8.0 years; 50% male) were recruited, and trialed Sleepfit for a 14-day intervention period between August 2021-January 2022. For all participants, there was a significant reduction in Insomnia Severity Index and Sleep Hygiene index scores after intervention engagement. Regression models demonstrated no significant intervention effect on sleep health or sleep hygiene outcomes (intervention versus waitlist control group). A high study drop-out rate (91.4%) prevented assessment of outcomes at 3-month follow-up.

Pilot trial findings demonstrate that Sleepfit may elicit improvements in sleep health and sleep hygiene outcomes amongst paramedic shiftworkers. However, low enrolment and retention means that findings should be interpreted with caution, further highlighting potential engagement challenges, especially among paramedics who are particularly in need of support for improved sleep.

Prospectively registered with the Australian New Zealand Clinical Trial Registry 24/01/2020 (reference no. ACTRN12620000059965).

Rhythmicity is a cornerstone of behavioral and biological processes, especially metabolism, yet the mechanisms behind metabolite cycling remain elusive. This study uncovers a robust oscillation in key metabolite pathways downstream of glucose in humans. A purpose-built 13C6-glucose isotope tracing platform was used to sample Drosophila every 4h and probe these pathways, revealing a striking peak in biosynthesis shortly after lights-on in wild-type flies. A hyperactive mutant (fumin) demonstrates increased Krebs cycle labelling and dawn-specific glycolysis labelling. Surprisingly, neither underlying feeding rhythms nor the presence of food availability explain the rhythmicity of glucose processing across genotypes, suggesting a robust internal mechanism for metabolic control of glucose processing. These results align with clinical data highlighting detrimental effects of mistimed energy intake. Our approach offers a unique insight into the dynamic range of daily metabolic processing and provides a mechanistic foundation for exploring circadian metabolic homeostasis in disease contexts.

Multiple common genetic variants have been associated with type 2 diabetes, but the mechanism by which they predispose to diabetes is incompletely understood. One such example is variation in MTNR1B, which implicates melatonin and its receptor in the pathogenesis of type 2 diabetes.

To characterize the effect of diabetes-associated genetic variation at rs10830963 in the MTNR1B locus on islet function in people without type 2 diabetes.

The association of genetic variation at rs10830963 with glucose, insulin, C-peptide, glucagon, and indices of insulin secretion and action were tested in a cohort of 294 individuals who had previously undergone an oral glucose tolerance test (OGTT). Insulin sensitivity, β-cell responsivity to glucose, and Disposition Indices were measured using the oral minimal model.

The Clinical Research and Translation Unit at Mayo Clinic, Rochester, MN.

Two cohorts were utilized for this analysis: 1 cohort was recruited on the basis of prior participation in a population-based study in Olmsted County. The other cohort was recruited on the basis of TCF7L2 genotype at rs7903146 from the Mayo Biobank.

Two-hour, 7-sample OGTT.

Fasting, nadir, and integrated glucagon concentrations.

One or 2 copies of the G-allele at rs10830963 were associated with increased postchallenge glucose and glucagon concentrations compared to subjects with the CC genotype.

The effects of rs10830963 on glucose homeostasis and predisposition to type 2 diabetes are likely to be partially mediated through changes in α-cell function.

Working at night is associated with adverse cardiometabolic health outcomes. However, there are a lack of nutritional intervention studies conducted amongst night workers, subsequently contributing to a lack of evidence-based guidelines for night workers. The aim of The Eating on the Night Shift study was to understand how night shift workers view working at night in relation to nutritional health and wellbeing, the barriers and enablers to participate in research and what kind of guidance would be useful to them. Semi-structured qualitative interviews were conducted with a convenience sample (n = 18) of night workers based in England. The interview covered experiences of working night shifts, perceptions about night work and their health, and perceptions of and likely engagement with nutritional research. Interviews were audio recorded and transcribed verbatim. Transcripts were coded using an inductive thematic analysis approach. Of the final sample 13 were female (72%), 39% worked a rotating shift pattern and 78% had worked night shifts for 1 year or more. Four overarching themes were identified: (1) the consequences of night work on health and wellbeing, (2) eating at night means a less healthy diet, (3) working at night has wider knock-on effects on aspects of lifestyle and wellbeing and (4) nutritional research is perceived as important, but there are barriers to participation. Night workers are aware that working at night can negatively impact their diet as well as their health. Nutritional researchers need to engage with night workers when considering intervention design and implementation as well as in the development of any resultant evidence-based guidance to ensure its relevance.

We previously reported that during a 45-day simulated space mission, a dynamic lighting schedule (DLS) improved circadian phase alignment and performance assessed once on selected days. This study aimed to evaluate how DLS affected performance on a 5-minute psychomotor vigilance task (PVT) administered multiple times per day on selected days.

Sixteen crewmembers (37.4 ± 6.7 years; 5F) underwent six cycles of 2 × 8-hour/night followed by 5 × 5-hour/night sleep opportunities. During the DLS (n = 8), daytime white light exposure was blue-enriched (~6000 K; Level 1: 1079, Level 2: 76 melanopic equivalent daytime illuminance (melEDI) lux) and blue-depleted (~3000-4000 K; L1: 21, L2: 2 melEDI lux) 3 hours before bed. In the standard lighting schedule (SLS; n = 8), lighting remained constant (~4500K; L1: 284, L2 62 melEDI lux). Effects of lighting condition (DLS/SLS), sleep condition (5/8 hours), time into mission, and their interactions, and time awake on PVT performance were analyzed using generalized linear mixed models.

The DLS was associated with fewer attentional lapses (reaction time [RT] > 500 milliseconds) compared to SLS. Lapses, mean RT, and 10% fastest/slowest RTs were worse following 5 compared to 8 hours of sleep but not between lighting conditions. There was an effect of time into mission on RTs, likely due to sleep loss. Overall performance differed by time of day, with longer RTs at the beginning and end of the day. There were more lapses and slower RTs in the afternoon in the SLS compared to the DLS condition.

Future missions should incorporate DLS to enhance circadian alignment and performance. This paper is part of the Sleep and Circadian Rhythms: Management of Fatigue in Occupational Settings Collection.

Malaria is a disease caused by infection with parasite Plasmodium spp. We studied the circadian regulation of host responses to the parasite, in a mouse model of cerebral malaria. The course of the disease was markedly affected by time of infection, with decreased parasitemia and increased inflammation upon infection in the middle of the night. At this time, there were fewer reticulocytes, which are target cells of the parasites. We next investigated the effects of desynchronization of host clocks on the infection: after 10 weeks of recurrent jet lags, mice showed decreased parasite growth and lack of parasite load rhythmicity, paralleled by a loss of glucose rhythm. Accordingly, disrupting host metabolic rhythms impacted parasite load rhythmicity. In summary, our findings of a circadian modulation of malaria parasite growth and infection shed light on aspects of the disease relevant to human malaria and could contribute to new therapeutic or prophylactic measures.

Stability in the timing of key daily routine behaviors such as working/doing housework, sleeping, eating, and engaging in social interactions (i.e., behavioral-social rhythms) contributes to health. This study examined whether behavioral-social rhythms were associated with cardiovascular disease (CVD) risk factors in retired night shift workers and retired day workers and explored whether past night shift work exposure moderated this association.

A total of 154 retired older adults participated in this study. Multiple logistic regression models were used to examine associations between behavioral-social rhythms and CVD risk factors. Independent variables included Social Rhythm Metric (SRM)-5 score and actigraphy rest-activity rhythm intradaily variability (IV) and interdaily stability (IS). Dependent variables were metabolic syndrome prevalence and its five individual components.

More regular behavioral-social rhythms were associated with lower odds of prevalent metabolic syndrome (SRM: odds ratio [OR] = 0.57, 95% confidence interval [CI] = 0.35-0.88; IV: OR = 4.00, 95% CI = 1.86-8.58; IS: OR = 0.42, 95% CI = 0.24-0.73) and two of its individual components: body mass index (SRM: OR = 0.56, 95% CI = 0.37-0.85; IV: OR = 2.84, 95% CI = 1.59-5.07; IS: OR = 0.42, 95% CI = 0.26-0.68) and high-density lipoprotein cholesterol (SRM: OR = 0.49, 95% CI = 0.30-0.80; IV: OR = 2.49, 95% CI = 1.25-4.96; IS: OR = 0.35, 95% CI = 0.19-0.66). Past shift work history did not moderate the association between behavioral-social rhythms and metabolic syndrome.

Behavioral-social rhythms were related to CVD risk factors in retired adults regardless of prior night shift work exposure. Older retired workers may benefit from education and interventions aiming to increase behavioral-social rhythm regularity.

This protocol paper outlines the methods that will be used to examine the impact of altering meal timing on metabolism, cognitive performance, and mood during the simulated night shift.

Participants (male and female) will be recruited according to an a priori selected sample size to complete a 7-day within and between participant's laboratory protocol. Participants will be randomly assigned to one of the three conditions: meal at night or snack at night or no meal at night. This protocol includes an 8-hour nighttime baseline sleep, followed by 4 consecutive nights of simulated nightshift (7 hours day sleep; 10:00-17:00 hours), and an 8-hour nighttime sleep (return to dayshift). During the simulated night shift, meals will be provided at ~06:30, 09:30, 14:10, and 19:00 hours (no eating at night); ~06:30, 19:00, and 00:30 hours (meal at night); or ~06:30, 14:10, 19:00, and 00:30 hours (snack at night). Meal composition will be strictly controlled throughout the study (45%-65% carbohydrates, 15%-25% protein, and 20%-35% fat per day) with daily energy provided to meet individual needs using the Harris-Benedict equation (light/sedentary activity). The primary outcome measures are serum concentrations of blood glucose, insulin, and free fatty acids area under the curve in response to the oral glucose tolerance test. Mixed-effect ANOVAs will be conducted.

This protocol paper describes a methodology to describe an innovative approach to reduce the metabolic disease impact associated with shift work.

Meal timing emerges as a crucial factor influencing metabolic health that can be explained by the tight interaction between the endogenous circadian clock and metabolic homeostasis. Mistimed food intake, such as delayed or nighttime consumption, leads to desynchronization of the internal circadian clock and is associated with an increased risk for obesity and associated metabolic disturbances such as type 2 diabetes and cardiovascular diseases. Conversely, meal timing aligned with cellular rhythms can optimize the performance of tissues and organs. In this review, we provide an overview of the metabolic effects of meal timing and discuss the underlying mechanisms. Additionally, we explore factors influencing meal timing, including internal determinants such as chronotype and genetics, as well as external influences like social factors, cultural aspects, and work schedules. This review could contribute to defining meal-timing-based recommendations for public health initiatives and developing guidelines for effective lifestyle modifications targeting the prevention and treatment of obesity and associated metabolic diseases. Furthermore, it sheds light on crucial factors that must be considered in the design of future food timing intervention trials.

Artificial light at night (ALAN) affects most of the population. Through the retinohypothalamic tract, ALAN modulates the activity of the central circadian oscillator and, consequently, various physiological systems, including the cardiovascular one. We summarised the current knowledge about the effects of ALAN on the cardiovascular system in diurnal and nocturnal animals. Based on published data, ALAN reduces the day-night variability of the blood pressure and heart rate in diurnal and nocturnal animals by increasing the nocturnal values of cardiovascular variables in diurnal animals and decreasing them in nocturnal animals. The effects of ALAN on the cardiovascular system are mainly transmitted through the autonomic nervous system. ALAN is also considered a stress-inducing factor, as glucocorticoid and glucose level changes indicate. Moreover, in nocturnal rats, ALAN increases the pressure response to load. In addition, ALAN induces molecular changes in the heart and blood vessels. Changes in the cardiovascular system significantly depend on the duration of ALAN exposure. To some extent, alterations in physical activity can explain the changes observed in the cardiovascular system after ALAN exposure. Although ALAN acts differently on nocturnal and diurnal animals, we can conclude that both exhibit a weakened circadian coordination among physiological systems, which increases the risk of future cardiovascular complications and reduces the ability to anticipate stress.

Meal timing plays a crucial role for cardiometabolic health, given the circadian regulation of cardiometabolic function. However, to the best of our knowledge, no concept of meal timing exists in traditional European medicine (TEM). Therefore, in this narrative review, we aim to define the optimal time slot for energy intake and optimal energy distribution throughout the day in a context of TEM and explore further implications. By reviewing literature published between 2002 and 2022, we found that optimal timing for energy intake may be between 06:00 and 09:00, 12:00 and 14:00, and between 15:00 and 18:00, with high energy breakfast, medium energy lunch and low energy dinner and possibly further adjustments according to one's chronotype and genetics. Also, timing and distribution of energy intake may serve as a novel therapeutic strategy to optimize coction, a concept describing digestion and metabolism in TEM. Please cite this article as: Eberli NS, Colas L, Gimalac A. Chrononutrition in traditional European medicine-Ideal meal timing for cardiometabolic health promotion. J Integr Med. 2024; 22(2);115-125.

Circadian rhythm disruption is associated with impaired glucose homeostasis and type 2 diabetes. For example, night shift work is associated with an increased risk of gestational diabetes. However, the effects of chronic circadian disruption since early life on adult metabolic health trajectory remain unknown. Here, using the "Short Day" (SD) mouse model, in which an 8 h/8 h light/dark (LD) cycle was used to disrupt mouse circadian rhythms across the lifespan, we investigated glucose homeostasis in adult mice. Adult SD mice were fully entrained into the 8 h/8 h LD cycle, and control mice were entrained into the 12 h/12 h LD cycle. Under a normal chow diet, female and male SD mice displayed a normal body weight trajectory. However, female but not male SD mice under a normal chow diet displayed glucose intolerance and insulin resistance, which are associated with impaired insulin signaling/AKT in the skeletal muscle and liver. Under high-fat diet (HFD) challenges, male but not female SD mice demonstrated increased body weight gain compared to controls. Both male and female SD mice developed glucose intolerance under HFD. Taken together, these results demonstrate that environmental disruption of circadian rhythms contributes to obesity in a sexually dimorphic manner but increases the risk of glucose intolerance and insulin resistance in both males and females.

Novel strategies are required to reduce the risk of developing diabetes and/or clinical outcomes and complications of diabetes. In this regard, the role of the circadian system may be a potential candidate for the prevention of diabetes. We reviewed evidence from animal, clinical, and epidemiological studies linking the circadian system to various aspects of the pathophysiology and clinical outcomes of diabetes. The circadian clock governs genetic, metabolic, hormonal, and behavioral signals in anticipation of cyclic 24-hour events through interactions between a "central clock" in the suprachiasmatic nucleus and "peripheral clocks" in the whole body. Currently, circadian rhythmicity in humans can be subjectively or objectively assessed by measuring melatonin and glucocorticoid levels, core body temperature, peripheral blood, oral mucosa, hair follicles, rest-activity cycles, sleep diaries, and circadian chronotypes. In this review, we summarized various circadian misalignments, such as altered light-dark, sleep-wake, rest-activity, fasting-feeding, shift work, evening chronotype, and social jetlag, as well as mutations in clock genes that could contribute to the development of diabetes and poor glycemic status in patients with diabetes. Targeting critical components of the circadian system could deliver potential candidates for the treatment and prevention of type 2 diabetes mellitus in the future.

Night shift workers are exposed to circadian disruption, which contributes to impaired glucose tolerance. Although fasting during the night shift improves glucose homeostasis, adhering to this dietary strategy may be challenging.

This study evaluated the effect of fasting compared with the consumption of meals with different combinations of glycemic index (GI, low or high) and frequency (1 or 3 times) during the night shift on continuous glucose monitoring metrics.

A 2-arm randomized cross-over trial was conducted on female nurses working night shifts. In each of those arms, the participants were either provided with no meal (fasted), low GI, or high-GI meal during the night shift with a meal frequency according to which arm they were randomly allocated to, either 1-MEAL or 3-MEAL. Outcome variables were glycemic control and variability (GC and GV) metrics during the night shift (21:30-7:00), in the morning after the night shift (07:00-13:00), and in the 24 h period (18:00-18:00).

Compared to no meal, the consumption of 1 high-GI meal increased all GV metrics not only during the night shifts but also in the morning, for instance, as observed in the coefficient of variation (β = 0.03 mmol/L; 95% CI: 0.01, 0.05), and GV percentage (β = 4.13; 95% CI: 2.07, 6.18). The consumption of 1 or 3 low GI meals did not raise GC or GV metrics except for continuous overall net glycemic action during the night shifts after consuming 3 low GI meals. When controlling for GI, night shift meal frequency did not affect any metrics in any timeframe.

High meal GI but not higher meal frequency during the night shift increased GC and GV in female night shift workers. Results for 1 low-GI meal during the night shift were not different from a glucose profile after no meal. This trial was registered at trialsearch.who.int as NL8715.

Individuals in the workplace are exposed to various environments, tasks, and schedules. Previous studies have indicated a link between occupational exposures and an increased risk of chronic kidney disease (CKD). However, the social conditions of the work environment may also be a crucial contributing factor to CKD. Furthermore, individuals may encounter multiple occupational-related risk factors simultaneously, underscoring the importance of investigating the joint risk of different working conditions on CKD.

A prospective analysis of 65,069 UK Biobank participants aged 40 to 69 years without CKD at baseline (2006-2010) was performed. A self-administered questionnaire assessed working conditions and a working conditions risk score were developed. Participants who answered "sometimes" or "often" exposure to occupational heat or occupational secondhand cigarette smoke; involved in shift work or heavy workloads ("usually" or "always"), were grouped as high-risk working conditions. Each working condition was scored as 1 if grouped as high-risk, and 0 if not. The working conditions risk score was equal to the sum of these four working conditions. Cox proportional hazard regression models were used to estimate the associations between working conditions and CKD incidence.

The mean follow-up time was 6.7 years. After adjusting for demographic, lifestyle, and working time factors, the hazard ratios for the development of CKD for heavy workloads, shift work, occupational secondhand cigarette smoke exposure, and occupational heat exposure were 1.24 (95%CI = 1.03, 1.51), 1.33 (95%CI = 1.10, 1.62), 1.13 (95%CI = 1.01, 1.26), 1.11 (95%CI = 0.99, 1.24), respectively. The risk of CKD was found to be significantly associated with an increasing working conditions risk score. Individuals with a working conditions risk score of 4 had an 88.0% (95% CI = 1.05, 3.35) higher risk of developing CKD when compared to those with a working conditions risk score of 0.

Adverse working conditions, particularly when considered in combination, can significantly elevate the risk of chronic kidney disease (CKD). These results provide a reference for implementing measures to prevent CKD.

Circadian rhythms are endogenous oscillations with approximately a 24-h period that allow organisms to anticipate the change between day and night. Disruptions that desynchronize or misalign circadian rhythms are associated with an increased risk of cardiometabolic disease. This review focuses on the liver circadian clock as relevant to the risk of developing metabolic diseases including nonalcoholic fatty liver disease (NAFLD), insulin resistance, and type 2 diabetes (T2D). Many liver functions exhibit rhythmicity. Approximately 40% of the hepatic transcriptome exhibits 24-h rhythms, along with rhythms in protein levels, posttranslational modification, and various metabolites. The liver circadian clock is critical for maintaining glucose and lipid homeostasis. Most of the attention in the metabolic field has been directed toward diet, exercise, and rather little to modifiable risks due to circadian misalignment or disruption. Therefore, the aim of this review is to systematically analyze the various approaches that study liver circadian pathways, targeting metabolic liver diseases, such as diabetes, nonalcoholic fatty liver disease, using human, rodent, and cell biology models.NEW & NOTEWORTHY Over the past decade, there has been an increased interest in understanding the intricate relationship between circadian rhythm and liver metabolism. In this review, we have systematically searched the literature to analyze the various experimental approaches utilizing human, rodent, and in vitro cellular approaches to dissect the link between liver circadian rhythms and metabolic disease.

The epidemic of obesity is associated with a substantial, complex and escalating burden of disease. Dietary and lifestyle interventions provide the mainstay of management; however, obesity is multifactorial and challenging to address clinically. Disrupted circadian behaviours, including late eating, are associated with obesity. Time-restricted feeding (TRF), the confinement of calorie intake to a temporal 'eating window', has received growing interest as a weight-loss intervention. Benefits are purported to arise from the fasting period and strengthened circadian metabolism. However, the current evidence-base for TRF is small-scale, limited, and there has been little evaluation of circadian schedule. This research aims to enable evidence-based conclusions regarding circadian-aligned TRF as a weight-loss intervention in obesity.

A systematic three-tranche search strategy was conducted within PubMed. Included studies were critically evaluated. Search tranches scoped: interventional evidence for TRF; evidence linking meal timing, obesity and metabolic function; and evidence linking circadian function, obesity, and dysmetabolism. Results were summarised in a narrative analysis.

A total of 30 studies were included. From small-scale and short-term evidence, TRF was consistently associated with improved weight, glycaemic and anthropometric outcomes versus baseline or control. Good adherence and safety, and consistency of results between studies, were notable. Earlier ('circadian-aligned') eating was associated with greater diet-induced thermogenesis, and improved weight loss and glycaemic outcomes. Limited evidence suggested meaningful correlations between circadian clock function and obesity/metabolic risk.

Circadian-aligned TRF may present a promising intervention for weight loss and metabolic benefits in obese/overweight individuals.

Achieving synchronization between the central and peripheral body clocks is essential for ensuring optimal metabolic function. Meal timing is an emerging field of research that investigates the influence of eating patterns on our circadian rhythm, metabolism, and overall health. This narrative review examines the relationship between meal timing, circadian rhythm, clock genes, circadian hormones, and metabolic function. It analyzes the existing literature and experimental data to explore the connection between mealtime, circadian rhythms, and metabolic processes. The available evidence highlights the importance of aligning mealtime with the body's natural rhythms to promote metabolic health and prevent metabolic disorders. Specifically, studies show that consuming meals later in the day is associated with an elevated prevalence of metabolic disorders, while early time-restricted eating, such as having an early breakfast and an earlier dinner, improves levels of glucose in the blood and substrate oxidation. Circadian hormones, including cortisol and melatonin, interact with mealtimes and play vital roles in regulating metabolic processes. Cortisol, aligned with dawn in diurnal mammals, activates energy reserves, stimulates appetite, influences clock gene expression, and synchronizes peripheral clocks. Consuming meals during periods of elevated melatonin levels, specifically during the circadian night, has been correlated with potential implications for glucose tolerance. Understanding the mechanisms of central and peripheral clock synchronization, including genetics, interactions with chronotype, sleep duration, and hormonal changes, provides valuable insights for optimizing dietary strategies and timing. This knowledge contributes to improved overall health and well-being by aligning mealtime with the body's natural circadian rhythm.

Shift workers typically experience misalignment between their circadian system and behavioral/environmental cycles and have an increased risk for obesity. Experimental studies in non-shift workers have suggested that circadian misalignment can disrupt energy balance regulation. This study examined the impact of circadian misalignment in the most relevant population, i.e., chronic shift workers.

Seven healthy chronic night shift workers underwent a randomized crossover study with two 3-day laboratory protocols: a night work protocol including 12-hour inverted behavioral/environmental cycles (circadian misalignment) and a day work protocol (circadian alignment).

Circadian misalignment led to a ~17% increase in 24-hour acylated ghrelin levels in the chronic shift workers (p = 0.009). Consistently, circadian misalignment resulted in ~14% higher hunger at breakfast in the night shift (p = 0.04). Circadian misalignment did not significantly change fasting and postprandial energy expenditure or respiratory exchange ratio (all p > 0.32). Unexpectedly, 24-hour behavioral activity levels were ~38% higher (p < 0.0001) during circadian misalignment, despite a concurrent increase in sleepiness (p = 0.03).

These results reveal that circadian misalignment, while carefully controlling for dietary intake, increases acylated ghrelin in chronic shift workers. Further studies should test whether the observed acute effects of circadian misalignment in chronic shift workers contribute to their increased obesity risk in the long term.

Shift work can cause circadian cycles disturbances and misaligns the endogenous rhythms. The physiological variables are driven by the circadian system and, its misalignment, can impair the metabolic functions. Thus, the main objective of this study was to evaluate the metabolic alterations as a result of shift work and night work reported in articles published in the last 5 years, using the eligibility criteria both gender and indexed articles in English language. In order to execute this work, we perform a systematic review according to PRISMA guidelines and searched about Chronobiology Disorders and Night Work, both related to metabolism, in Medline, Lilacs, ScienceDirect and Cochrane. Cross-sectional, cohort and experimental studies with low risk of bias were included. We found a total of 132 articles, and, after the selection process, 16 articles remained to be analyzed. It was observed that shift work can cause circadian misalignment and, consequently, some metabolic parameters alterations such as an impaired glycemic control and insulin functioning, cortisol phase release, cholesterol fractions imbalance, changes in morphological indexes and melatonin secretion. There are some limitations, such as heterogenicity in used databases and the 5 years restriction period, because the effects of sleep disturbance may have been reported earlier. In conclusion, we suggest that shift work interferes with the sleep-wake cycle and eating patterns, which cause crucial physiological alterations that, together, can lead to metabolic syndrome.

Circadian rhythms that influence mammalian homeostasis and overall health have received increasing interest over the past two decades. The molecular clock, which is present in almost every cell, drives circadian rhythms while being a cornerstone of physiological outcomes. The skeletal muscle clock has emerged as a primary contributor to metabolic health, as the coordinated expression of the core clock factors BMAL1 and CLOCK with the muscle-specific transcription factor MYOD1 facilitates the circadian and metabolic programme that supports skeletal muscle physiology. The phase of the skeletal muscle clock is sensitive to the time of exercise, which provides a rationale for exploring the interactions between the skeletal muscle clock, exercise and metabolic health. Here, we review the underlying mechanisms of the skeletal muscle clock that drive muscle physiology, with a particular focus on metabolic health. Additionally, we highlight the interaction between exercise and the skeletal muscle clock as a means of reinforcing metabolic health and discuss the possible implications of the time of exercise as a chronotherapeutic approach.

Circadian rhythms are generated by the circadian clock, a self-sustained internal timing system that exhibits 24-h rhythms in the body. Many metabolic, cellular, behavioral and physiological processes are regulated by the circadian clock in coordination with environmental cues. The present study is a comprehensive review of the currently existing evidence concerning the relationship between circadian rhythms and sleep, metabolic, and cardiovascular disorders. We thoroughly searched the online databases PubMed, Scopus, and Web of Science to find the existing clinical studies from the last twenty-three years (2000-2023). Circadian misalignment was found to be associated with an increase in the risk of metabolic disorders, cardiovascular diseases, and obesity, as well as inadequate sleep quality. In this review article, all the included studies had a strength protocol design and all of them were conducted on humans. However, the most common limitations of them were the small sample size and the short time of the intervention. In conclusion, managing the factors that disrupt the optimal function of central and peripheral clocks can help to reduce the risk of metabolic and cardiovascular diseases, improving also sleep quality. Future studies should further explore the underlying mechanisms of the interconnections between circadian clocks and sleep, metabolic, and cardiovascular disorders. This may provide new opportunities for advance chronotherapy approach.

Shift workers face an increased risk of metabolic health problems, but the direct metabolic response to working nights is not fully understood. The aim of this study was to investigate the effect of night shifts on the 24-h urinary metabolome of shift workers. Eleven police officers working rotating shifts completed two 24-h laboratory visits that took place before and after they worked 7 consecutive nights. Sleep and meals were scheduled on a day schedule in the first visit and then on a night schedule (i.e., sleep and meals shifted by approximately 12 h) in the second visit. Targeted metabolomic analysis was performed on urine samples collected throughout these laboratory visits. Differential rhythmicity analysis was used to compare 24-h rhythms in urinary metabolites in both conditions. Our results show that on the day schedule, 24-h rhythms are present in the urinary levels of the majority of metabolites, but that this is significantly reduced on the night schedule, partly due to loss of organic acid rhythmicity. Furthermore, misalignment of 24-h metabolite rhythms with the shifted behavioral cycles in the night schedule was observed in more than half of the metabolites that were rhythmic in both conditions (all acylcarnitines). These results show that working nights alters the daily rhythms of the urinary metabolome in rotating shift workers, with the most notable impact observed for acylcarnitines and organic acids, 2 metabolite classes involved in mitochondrial function. Further research is warranted to study how these changes relate to the increased metabolic risks associated with shift work.

Glucose tolerance is controlled by the internal clock and is worse in the evening. From a chrononutrition perspective, diabetes prevention requires evaluating the antidiabetic effects of the timing of functional ingredients and nutrient intake. The purpose of this study was to investigate the timing effects of acute mulberry leaf extract (MLE) intake on postprandial glucose levels in young adults.

Twelve young adults underwent four trials. Blood samples were collected in a fasting state and at 30, 60, 120, and 180 min after eating a mixed meal. The study had a randomised, placebo-controlled, double-blind trial design involving: (1) morning placebo trial (08:00 h; MP trial), (2) evening placebo trial (18:00 h; EP trial), (3) morning MLE trial (08:00 h; MM trial), and (4) evening MLE trial (18:00 h; EM trial).

The incremental area under the blood glucose curve (iAUC) in the EM trials was significantly lower than that in the EP trials (P = 0.010). The postprandial glucose concentrations 120 min after the meal were significantly lower in the EM trials than those in the EP trials (P = 0.006). The postprandial insulin concentrations at 120 min were significantly lower in the MM trials than those in the MP trials (P = 0.034). Moreover, the postprandial insulin concentrations 180 min after the meal were significantly lower in the EM trials than those in the EP trials (P = 0.034).

MLE intake in the evening, but not in the morning, was effective in improving glucose tolerance.

Clinical trial reference: UMIN 000045301; website of trial registry: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000051340 .

Obstructive sleep apnea (OSA) is a chronic disorder characterized by recurrent episodes of apnea and hypopnea during sleep. It is associated with various cardiovascular and metabolic complications, including type 2 diabetes mellitus (T2DM) and obesity. Many pathways can be responsible for T2DM development in OSA patients, e.g., those related to HIF-1 and SIRT1 expression. Moreover, epigenetic mechanisms, such as miRNA181a or miRNA199, are postulated to play a pivotal role in this link. It has been proven that OSA increases the occurrence of circadian clock disruption, which is also a risk factor for metabolic disease development. Circadian clock disruption impairs the metabolism of glucose, lipids, and the secretion of bile acids. Therefore, OSA-induced circadian clock disruption may be a potential, complex, underlying pathway involved in developing and exacerbating metabolic diseases among OSA patients. The current paper summarizes the available information pertaining to the relationship between OSA and circadian clock disruption in the context of potential mechanisms leading to metabolic disorders.

Circadian rhythms drive our daily behaviors to coincide with the earth's rotation on an approximate 24-h cycle. The circadian clock mechanism present in nearly every cell is responsible for our circadian rhythms and is comprised of a transcriptional-translational feedback loop in mammals. The central clock resides in the hypothalamus responding to external light cues, whereas peripheral clocks receive signals from the central clock and are also sensitive to cues from feeding and activity. Of the peripheral clocks, the skeletal muscle clock is particularly sensitive to exercise which has shown to be an important time-cue with the ability to influence and adjust the muscle clock phase in response to exercise timing. Since the skeletal muscle clock is also involved in the expression of tissue-specific gene expression-including glucoregulatory genes-this might suggest a role for exercise timing as a therapeutic strategy in metabolic diseases, like type 2 diabetes. Notably, those with type 2 diabetes have accompanied disruptions in their skeletal muscle clock mechanism which may also be related to the increased risk of type 2 diabetes seen among shift workers. Therefore, the direct influence of exercise on the skeletal muscle clock might support the use of exercise timing to provide disease-mitigating effects. Here, we highlight the potential use of time-of-day exercise as a chronotherapeutic tool within circadian medicine to improve the metabolic profile of type 2 diabetes and support long-term glycemic control, potentially working through the skeletal muscle clock and circadian physiology.

Youth-onset obesity is associated with negative health outcomes across the lifespan including cardiovascular diseases, type 2 diabetes, obstructive sleep apnea, dyslipidemias, asthma, and several cancers. Pediatric health guidelines have traditionally focused on the quality and quantity of dietary intake, physical activity, and sleep.

Emerging evidence suggests that the timing (time of day when behavior occurs) and composition (proportion of time spent allocated to behavior) of food intake, movement (i.e., physical activity, sedentary time), and sleep may independently predict health trajectories and disease risks. Several theoretically driven interventions and conceptual frameworks feature behavior timing and composition (e.g., 24 h movement continuum, circadian science and chronobiology, intermittent fasting regimens, structured day hypothesis). These literatures are, however, disparate, with little crosstalk across disciplines. In this review, we examine dietary, sleep, and movement guidelines and recommendations for youths ages 0-18 in the context of theoretical models and empirical findings in support of time-based approaches. The review aims to inform a unifying framework of health behaviors and guide future research on the integration of time-based recommendations into current quantity and quality-based health guidelines for children and adolescents.

The importance of the circadian clock in maintaining human health is now widely acknowledged. Dysregulated and dampened clocks may be a common cause of age-related diseases and metabolic syndrome Thus, circadian clocks should be considered as therapeutic targets to mitigate disease symptoms. This review highlights a number of dietary compounds that positively affect the maintenance of the circadian clock. Notably the polymethoxyflavone nobiletin has shown some encouraging results in pre-clinical experiments. Although many more experiments are needed to fully elucidate its exact mechanism of action, it is a promising candidate with potential as a chronotherapeutic agent.

Actigraphy-based sleep detection algorithms were mostly validated using nighttime sleep, and their performance in detecting daytime sleep is unclear. We evaluated and compared the performance of Actiware and the Cole-Kripke algorithm (C-K) - two commonly used actigraphy-based algorithms - in detecting daytime and nighttime sleep.

Twenty-five healthy young adults were monitored by polysomnography and actigraphy during two in-lab protocols with scheduled nighttime and/or daytime sleep (within-subject design). Mixed-effect models were conducted to compare the sensitivity, specificity, and F1 score (a less-biased measure of accuracy) of Actiware (with low/medium/high threshold setting, separately) and C-K in detecting sleep epochs from actigraphy recordings during nighttime/daytime. t-tests and intraclass correlation coefficients were used to assess the agreement between actigraphy-based algorithms and polysomnography in scoring total sleep time (TST).

Sensitivity was similar between nighttime (Actiware: 0.93-0.99 across threshold settings; C-K: 0.61) and daytime sleep (Actiware: 0.93-0.99; C-K: 0.66) for both the C-K and Actiware (daytime/nighttime×algorithm interaction: p > 0.1). Specificity for daytime sleep was lower (Actiware: 0.35-0.54; C-K: 0.91) than that for nighttime sleep (Actiware: 0.37-0.62; C-K: 0.93; p = 0.001). Specificity was also higher for C-K than Actiware (p < 0.001), with no daytime/nighttime×algorithm interaction (p > 0.1). C-K had lower F1 (nighttime = 0.74; daytime = 0.77) than Actiware (nighttime = 0.95-0.98; daytime = 0.90-0.91) for both nighttime and daytime sleep (all p < 0.05). The daytime-nighttime difference in F1 was opposite for Actiware (daytime: 0.90-0.91; nighttime: 0.95-0.98) and C-K (daytime: 0.77; nighttime: 0.74; interaction p = 0.003). Bias in TST was lowest in Actiware (with medium-threshold) for nighttime sleep (underestimation of 5.99 min/8h) and in Actiware (with low-threshold) for daytime sleep (overestimation of 17.75 min/8h).

Daytime/nighttime sleep affected specificity and F1 but not sensitivity of actigraphy-based sleep scoring. Overall, Actiware performed better than the C-K algorithm. Actiware with medium-threshold was the least biased in estimating nighttime TST, and Actiware with low-threshold was the least biased in estimating daytime TST.

Circadian rhythms are endogenous oscillations, widely found across biological species, that have the capability of entraining to the 24-h light-dark cycle. Circadian systems often consist of both central oscillators that receive direct light-dark input and peripheral oscillators that receive input from the central oscillators. In this paper, we address questions related to what governs the time to and pattern of entrainment of these hierarchical circadian systems after an abrupt switch in the light-dark phasing. For a network consisting of a single central oscillator coupled to a chain of N feed-forward peripheral oscillators, we introduce a systematic way to derive an N-dimensional entrainment map whose fixed points correspond to entrained solutions. Using the map, we explain that the direction of reentrainment can involve fairly complicated phase advancing and delaying behavior as well as reentrainment times that depend sensitively on the nature of the perturbation. We also study the dynamics of a hierarchical system in which the peripheral oscillators are mutually coupled. We study how reentrainment times vary as a function of the degree to which the oscillators are desynchronized at the time of the change in light-dark phasing. We show that desynchronizing the peripheral oscillators can, in some circumstances, speed up their ultimate reentrainment following perturbations.

The circadian system is responsible for internal functions and regulation of the organism according to environmental cues (zeitgebers). Circadian rhythm dysregulation or chronodisruption has been associated with several diseases, from mental to autoimmune diseases, and with life quality change. Following this, some therapies have been developed to correct circadian misalignments, such as light therapy and chronobiotics. In this manuscript, we describe the circadian-related diseases so far investigated, and studies reporting relevant data on this topic, evidencing this relationship, are included. Despite the actual limitations in published work, there is clear evidence of the correlation between circadian rhythm dysregulation and disease origin/development, and, in this way, clock-related therapies emerge as great progress in the clinical field. Future improvements in such interventions can lead to the development of successful chronotherapy strategies, deeply contributing to enhanced therapeutic outcomes.