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Approaches to the Pharmacological Management of Jet Lag.

ABSTRACT: For many years now a treatment mitigating the debilitating effects of jet lag has been sought. Rapid travel across time zones leads, in most people, to temporary symptoms, in particular poor sleep, daytime alertness and poor performance. Mis-timed circadian rhythms are considered to be the main factor underlying jet-lag symptoms, together with the sleep deprivation from long haul flights. Virtually all aspects of physiology are rhythmic, from cells to systems, and circadian rhythms are coordinated by a central pacemaker or clock in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN adapts slowly to changes in time zone, and peripheral clocks or oscillators adapt at different rates, such that the organism is in a state of desynchrony from the external environment and internally. Light exposure is the main factor controlling the circadian system and needs to be considered together with any pharmacological interventions. This review covers the relatively new chronobiotic drugs, which can hasten adaptation of the circadian system, together with drugs directly affecting alertness and sleep propensity. No current treatment can instantly shift circadian phase to a new time zone; however, adaptation can be hastened. The melatoninergic drugs are promising but larger trials in real-life situations are needed. For short stopovers it is recommended to preserve sleep and alertness without necessarily modifying the circadian system. New research suggests that modification of clock function via genetic manipulation may one day have clinical applications.

SUBMITTER: Arendt J

PROVIDER: S-EPMC6182450 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Approaches to the Pharmacological Management of Jet Lag.

Arendt Josephine J

Drugs 20180901 14

For many years now a treatment mitigating the debilitating effects of jet lag has been sought. Rapid travel across time zones leads, in most people, to temporary symptoms, in particular poor sleep, daytime alertness and poor performance. Mis-timed circadian rhythms are considered to be the main factor underlying jet-lag symptoms, together with the sleep deprivation from long haul flights. Virtually all aspects of physiology are rhythmic, from cells to systems, and circadian rhythms are coordinat ...[more]

PMID: 30167980

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Project description:BackgroundEvidence suggests that circadian rhythm disorder is associated with a variety of gastrointestinal diseases, and the circadian rhythm plays a key role in maintaining the homeostasis of intestinal flora. The underlying mechanisms are still not completely identified. This study was aimed to explore whether jet lag-caused circadian disruption influences gut microbiome and its metabolites.MethodsMice were synchronized with 12-h light/dark cycles (control group) or subjected to daily 8-h advance of the light/dark cycle for every 3 days (jet-lagged group). Four months later, fecal samples and jejunal contents were collected and analyzed by 16S rRNA gene sequencing. In addition, fecal samples were subjected to metabolome analysis with ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).ResultsThe results of 16s rRNA sequencing showed that chronic jet lag led to decreased microbial abundance, richness, and diversity in both feces and jejunal contents. ANOSIM analysis revealed significant difference between control and jet-lagged groups. As the colonic microbiome, the abundance of Bacteroidetes phylum was significantly decreased and that of Actinobacteria phylum was increased in jet-lagged mice. Jet lag increased the ratio of Firmicutes to Bacteroidetes, an indicator for the imbalance of gut microbiota. Metabolome analysis of fecal samples showed that the levels of tryptophan and its derivatives were decreased in jet-lagged mice. In addition, fecal levels of secondary bile acids changed under jet lag conditions. Correlation analysis identified associations between tryptophan (and its derivatives) levels and colonic microbiota.ConclusionsThis study presents a comprehensive landscape of gut microbiota and its metabolites in mice subjected to chronic jet lag. The results suggest that circadian disruption may lead to changes in fecal and jejunal microbiota and fecal metabolites. Moreover, our results demonstrate a novel interplay between the gut microbiome and metabolome.

Project description:Importance:Inadequate sleep duration and quality increase the risk of obesity. Sleep timing, while less studied, is important in adolescents because increasing evening preferences (chronotypes), early school start times, and irregular sleep schedules may cause circadian misalignment. Objective:To investigate associations of chronotype and social jet lag with adiposity and cardiometabolic risk in young adolescents. Design, Setting, and Participants:Starting in 1999, Project Viva recruited pregnant women from eastern Massachusetts. Mother-child in-person visits occurred throughout childhood. From January 23, 2012, to October 16, 2016, 804 adolescents aged 12 to 17 years completed 5 days or more of wrist actigraphy, questionnaires, and anthropometric measurements. A cross-sectional analysis using these data was conducted from April 31, 2018, to May 1, 2019. Exposures:Chronotype, measured via a continuous scale with higher scores indicating greater evening preferences, and social jet lag, measured as the continuous difference in actigraphy sleep midpoint in hours from midnight on weekends vs weekdays, with higher values representing more delayed sleep timing on weekends. Main Outcomes and Measures:Adiposity, measured via anthropometry and dual-energy x-ray absorptiometry. For a subset of 479 adolescents with blood samples, cardiometabolic risk scores were computed as the mean of 5 sex- and cohort-specific z scores for waist circumference, systolic blood pressure, inversely scaled high-density lipoprotein cholesterol, and log-transformed triglycerides and homeostatic model of insulin resistance. Results:Among the 804 adolescents in the study, 418 were girls and 386 were boys, with a mean (SD) age of 13.2 (0.9) years. In multivariable models adjusted for age, puberty, season, and sociodemographics, associations of chronotype and social jet lag with adiposity varied by sex. For girls, greater evening preference was associated with a 0.58-cm (95% CI, 0.12-1.03 cm; P?=?.04 for interaction) higher waist circumference and 0.16 kg/m2 (95% CI, 0.01-0.31 kg/m2; P?=?.03 for interaction) higher fat mass index as measured by dual-energy x-ray absorptiometry; each hour of social jet lag was associated with a 1.19-cm (95% CI, 0.04-2.35 cm; P?=?.21 for interaction) higher waist circumference and 0.45 kg/m2 (95% CI, 0.09-0.82 kg/m2; P?=?.01 for interaction) higher fat mass index as measured by dual-energy x-ray absorptiometry. Associations of social jet lag and evening chronotypes persisted for many measures of adiposity after adjustment for sleep duration and other lifestyle behaviors. By contrast, no associations were observed in boys. There were no associations with the cardiometabolic risk score for either sex, although statistical power was low for this outcome. Conclusions and Relevance:Evening chronotypes and social jet lag were associated with greater adiposity in adolescent girls but not adolescent boys. Interventions aimed at improving sleep schedules may be useful for obesity prevention, especially in girls.

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Approaches to the Pharmacological Management of Jet Lag.

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Approaches to the Pharmacological Management of Jet Lag.

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