[Research progress of circadian rhythm].

Circadian rhythm disorder is a common society issue caused by jet lag,shift work,sleep disruption and changes in food consumption. Light is the major factor affecting the circadian rhythm system. Disruption of the circadian rhythm system can cause damage to the body,leading to some diseases. Maintaining a normal circadian system is of great importance for good health. Ideal therapeutic effect can not only alleviate symptoms of the diseases,but also recovery the disturbed circadian rhythm to normal. The paper summarizes the modeling methods of animal circadian rhythm disorder,diseases of circadian rhythm abnormality,regulation of circadian clock genes and medicine which are related to circadian rhythm to diseases of circadian rhythm disorder.

Efficacy of Functional Foods, Beverages, and Supplements Claiming to Alleviate Air Travel Symptoms: Systematic Review and Meta-Analysis.

Airline passengers experience a range of symptoms when travelling on long flights. This review evaluated the efficacy of functional foods, beverages, and supplements claiming to address the effects of air travel for healthy adults. Products were identified in a scoping review of electronic databases, search engines, and grey literature (March to August 2019). A systematic review of the efficacy of product ingredients was conducted using five electronic databases from inception to February 2021. Articles were screened, data extracted, and assessed for risk of bias by two researchers independently. Meta-analysis was performed. Of the 3842 studies identified, 23 met selection criteria: melatonin (n = 10), Pycnogenol (n = 4), various macronutrients (n = 2), caffeine (n = 2), Centella asiatica (n = 1), elderberry (n = 1), Echinacea (n = 1), fluid (n = 1), and Pinokinase (n = 1). Meta-analysis (random effects model) indicated melatonin reduced self-reported jetlag following eastbound (n = 5) and westbound (n = 4) flights: standard mean difference -0.76 (95% CI = -1.06 to -0.45, I2 0%, p < 0.00001) and -0.66 (95% CI = -1.07 to -0.26, I2 45%, p = 0.001), respectively. Pycnogenol also reduced edema scores (n = 3), standard mean -4.09 (95% CI = -6.44 to -1.74), I2 98%, p = 0.0006). Overall, 12 of 183 ingredients contained in 199 products had evidence to support claims.

How to manage travel fatigue and jet lag in athletes? A systematic review of interventions.

OBJECTIVES: We investigated the management of travel fatigue and jet lag in athlete populations by evaluating studies that have applied non-pharmacological interventions (exercise, sleep, light and nutrition), and pharmacological interventions (melatonin, sedatives, stimulants, melatonin analogues, glucocorticoids and antihistamines) following long-haul transmeridian travel-based, or laboratory-based circadian system phase-shifts. DESIGN: Systematic review Eligibility criteria Randomised controlled trials (RCTs), and non-RCTs including experimental studies and observational studies, exploring interventions to manage travel fatigue and jet lag involving actual travel-based or laboratory-based phase-shifts. Studies included participants who were athletes, except for interventions rendering no athlete studies, then the search was expanded to include studies on healthy populations. DATA SOURCES: Electronic searches in PubMed, MEDLINE, CINAHL, Google Scholar and SPORTDiscus from inception to March 2019. We assessed included articles for risk of bias, methodological quality, level of evidence and quality of evidence. RESULTS: Twenty-two articles were included: 8 non-RCTs and 14 RCTs. No relevant travel fatigue papers were found. For jet lag, only 12 athlete-specific studies were available (six non-RCTs, six RCTs). In total (athletes and healthy populations), 11 non-pharmacological studies (participants 600; intervention group 290; four non-RCTs, seven RCTs) and 11 pharmacological studies (participants 1202; intervention group 870; four non-RCTs, seven RCTs) were included. For non-pharmacological interventions, seven studies across interventions related to actual travel and four to simulated travel. For pharmacological interventions, eight studies were based on actual travel and three on simulated travel. CONCLUSIONS: We found no literature pertaining to the management of travel fatigue. Evidence for the successful management of jet lag in athletes was of low quality. More field-based studies specifically on athlete populations are required with a multifaceted approach, better design and implementation to draw valid conclusions. PROSPERO registration number The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42019126852).

Approaches to the Pharmacological Management of Jet Lag.

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.

Preventive effect of L-carnitine on the disorder of lipid metabolism and circadian clock of mice subjected to chronic jet-lag.

Circadian clock plays an essential role in orchestrating daily physiology, and its disruption can evoke metabolic diseases such as obesity. L-Carnitine can reduce blood lipid levels, and ameliorate fatty liver through regulating lipid metabolism. However, whether L-Carnitine administration may affect the disturbance of lipid metabolism and circadian rhythm of mice induced by prolonged circadian disruption is still unknown. Herein, we investigated the effects of L-Carnitine on conditions of circadian clock and lipid metabolism through a chronic jet-lag mice model which was developed by reversing 12 h light/12 h dark cycle every 4 days for a continuous 12 weeks. Results showed that L-Carnitine administration significantly decreased levels of serum glutamic-oxaloacetic transaminase (GOT) and triglycerides (TG), which were remarkably elevated by chronic jet-lag. More importantly, quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that L-Carnitine supplementation would effectively counteract the negative alterations in gene expression which related to lipid metabolism (Srebp1, Acaca, Fasn, and Scd1), metabolic regulator (mTOR) and circadian rhythm (Bmal1, Per1, Cry1 and Dec1) in the liver of mice subjected to the chronic jet-lag. As a conclusion, L-Carnitine was partly effective in preventing the disruption of circadian clock and lipid metabolic disorders induced by the chronic jet-lag.

Potent Effects of Flavonoid Nobiletin on Amplitude, Period, and Phase of the Circadian Clock Rhythm in PER2::LUCIFERASE Mouse Embryonic Fibroblasts.

Flavonoids are natural polyphenols that are widely found in plants. The effects of flavonoids on obesity and numerous diseases such as cancer, diabetes, and Alzheimer's have been well studied. However, little is known about the relationships between flavonoids and the circadian clock. In this study, we show that continuous or transient application of flavonoids to the culture medium of embryonic fibroblasts from PER2::LUCIFERASE (PER2::LUC) mice induced various modifications in the circadian clock amplitude, period, and phase. Transient application of some of the tested flavonoids to cultured cells induced a phase delay of the PER2::LUC rhythm at the down slope phase. In addition, continuous application of the polymethoxy flavonoids nobiletin and tangeretin increased the amplitude and lengthened the period of the PER2::LUC rhythm. The nobiletin-induced phase delay was blocked by co-treatment with U0126, an ERK inhibitor. In summary, among the tested flavonoids, polymethoxy flavones increased the amplitude, lengthened the period, and delayed the phase of the PER2::LUC circadian rhythm. Therefore, foods that contain polymethoxy flavones may have beneficial effects on circadian rhythm disorders and jet lag.

TRANSMERIDIAN JET LAG AND ITS PHARMACOLOGICAL CORRECTION.

The article deals with the development and correction of acute jet lag in a flight across several time zones. The investigation had the purpose to study dynamics of subjective and objective psychophysiological parameters and demonstrate methods of prophylaxis and correction of acute jet lag due to transmerdian flights. Subjects were 8 normal volunteers (experimental group) at the age of 26-55 years flying eastward over 7 times zones. The investigation included 3 stages: baseline, preparatory (21-d course of Euricoma longifolia extraction) and main (intake of donormil, cirkadin and artificial sleep during the flight). Functional diagnostics was performed on the baseline stage, on completion of the preparatory stage and on the next day after the flight (21-22 days from the beginning of the preparatory stage). Objective and subjective methods were used to evaluate the autonomic and cardiovascular systems and mental performance. In the control group (n = 4) functional diagnostics was performed on the same days. The investigations showed the benefit of preparation for transmeridian air travel and experimentally demonstrated positive effects of the proposed pharmacological correction of acute transmeridian jet lag.

Glucocorticoids entrain molecular clock components in human peripheral cells.

In humans, shift work induces a desynchronization between the circadian system and the outside world, which contributes to shift work-associated medical disorders. Using a simulated night shift experiment, we previously showed that 3 d of bright light at night fully synchronize the central clock to the inverted sleep schedule, whereas the peripheral clocks located in peripheral blood mononuclear cells (PBMCs) took longer to reset. This underlines the need for testing the effects of synchronizers on both the central and peripheral clocks. Glucocorticoids display circadian rhythms controlled by the central clock and are thought to act as synchronizers of rodent peripheral clocks. In the present study, we tested whether the human central and peripheral clocks were sensitive to exogenous glucocorticoids (Cortef) administered in the late afternoon. We showed that 20 mg Cortef taken orally acutely increased PER1 expression in PBMC peripheral clocks. After 6 d of Cortef administration, the phases of central markers were not affected, whereas those of PER2-3 and BMAL1 expression in PBMCs were shifted by ∼ 9.5-11.5 h. These results demonstrate, for the first time, that human peripheral clocks are entrained by glucocorticoids. Importantly, they suggest innovative interventions for shift workers and jet-lag travelers, combining synchronizing agents for the central and peripheral clocks.

Is melatonin useful for jet lag?

Jet lag syndrome is an exogenous circadian rhythm sleep disorder, frequently reported in travelers who cross multiple time zones in a short period of time. Oral melatonin -a pineal neurohormone normally produced during darkness and responsible for regulating the body's circadian rhythms- has been used as treatment for this condition. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews including 11 randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded the use of oral melatonin probably reduces symptoms associated with jet lag syndrome. It is not clear whether its use produces adverse effects; however, these would be probably mild.

El jet lag es un trastorno exógeno del sueño y el ritmo circadiano que ocurre frecuentemente en viajeros que cruzan múltiples zonas horarias en un tiempo reducido. La administración de melatonina oral, neurohormona epifisiaria relacionada con la regulación de ritmos circadianos, se ha utilizado con el fin de disminuir los síntomas que caracterizan esta condición. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, encontramos cuatro revisiones sistemáticas que en conjunto incluyen 11 estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que la administración de melatonina oral probablemente disminuye los síntomas asociados al jet lag, y que no está claro si se asocia a efectos adversos, aunque estos serían leves.

Jet lag.

INTRODUCTION: Jet lag is a syndrome caused by disruption of the 'body clock', and affects most air travellers crossing five or more time zones; it is worse on eastward than on westward flights. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to prevent or minimise jet lag? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found five studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: hypnotics, lifestyle and environmental adaptations, and melatonin.

[Vasopressin and jet lag disordes]. / Wazopresyna a jet lag.

Circadian rhythm plays an important role in human physiology. Its abnormal functioning results, among others, in jet lag disorder (JLD- Jet Lag Disorder), which is a discomfort experienced by people travelling between time zones, as well as being the cause for metabolic diseases in people working shifts. Recent studies have shown the role of vasopressin V1a and V1b suprachiasmatic nucleus (SCN- surachiasmatic nucleus) of the hypothalamus in the regulation of circadian rhythms. Mice genetically lacking receptors are resistant to disturbances of circadian rhythm, and are characterized by an almost immediate adjustment to the new rhythm. A similar effect is achieved by pharmacologically blocking V1a and V1b receptors. Research gives hope of overcoming this disorder to travellers who traverse time zones at high speed, as well as creating the possibility of adaptation to shift work without provoking any negative consequences over one´s health.

Jet lag and travel fatigue: a comprehensive management plan for sport medicine physicians and high-performance support teams.

The impact of transcontinental travel and high-volume travel on athletes can result in physiologic disturbances and a complicated set of physical symptoms. Jet lag and travel fatigue have been identified by athletes, athletic trainers, coaches, and physicians as important but challenging problems that could benefit from practical solutions. Currently, there is a culture of disregard and lack of knowledge regarding the negative effects of jet lag and travel fatigue on the athlete's well-being and performance. In addition, the key physiologic metric (determination of the human circadian phase) that guides jet lag treatment interventions is elusive and thus limits evidence-based therapeutic advice. A better understanding of preflight, in-flight, and postflight management options, such as use of melatonin or the judicious application of sedatives, is important for the sports clinician to help athletes limit fatigue symptoms and maintain optimal performance. The purpose of this article was to provide a practical applied method of implementing a travel management program for athletic teams.

[Clinical picture and treatment of jet lag]. / Az idoeltolódás okozta tünetek (jet lag, "idozóna-baj") klinikai képe és kezelésének lehetoségei.

Symptoms associated with rapid time zone crosses represent one of the major health problems associated with commercial flights. This condition is termed jet lag that is characterized by sleep disturbances (insomnia, sleepiness), somatic symptoms, and decrease in mental and physical outputs. Difference between the light-darkness cycles of the destination and internal homeostatic rhythm is responsible for the syndrome. Restitution of the internal rhythm by appropriate light exposure or melatonin, optimal sleep time and duration, and drugs can be used in its treatment.

Melatonina y jet lag ¿un suplemento alimenticio o un principio activo de interés militar? / No disponible

No disponible

The international athlete--advances in management of jet lag disorder and anti-doping policy.

To perform at the highest level of international competition, athletes need to maximize rest during long travel, and expeditiously overcome the detrimental effects of "jet lag" (JL). The negative effects of JL may be alleviated by adopting a multimodality approach, including the judicious use of melatonin and other pharmacologic agents to aid re-entrainment and improve sleep characteristics. Strict compliance with anti-doping policy is pivotal before and during competition. There have been several recent updates regarding the use of selected medications, which mandate constant vigilance by sports medicine personnel to both evaluate drug efficacy and judiciously prescribe approved medications. It is critical that medical staff maintain familiarity and awareness on a continual basis to effectively educate athletes and support staff.

Jet lag, circadian rhythm sleep disturbances, and depression: the role of melatonin and its analogs.

Traveling through several time zones results in a constellation of symptoms known as jet lag. These include reduced alertness, daytime fatigue, loss of appetite, reduced cognitive skills, and disruption of the sleep/wake cycle. In susceptible air travel passengers, jet lag may exacerbate affective illness and result in psychiatric morbidity. Dysregulation of circadian rhythms and melatonin secretion represent the common underlying factor in jet lag and other circadian disorders. Recent studies have established the effectiveness of strategically timed administration of melatonin and appropriate timed exposure to environmental schedules including light in counteracting the dysregulation (chronobiologic actions). With the introduction of melatonergic agonists such as ramelteon and tasimelteon, which have both a stronger affinity for MT1 and MT2 melatonin receptors and a longer half-life, new therapeutic options now exist for treating the sleep disturbances associated with jet lag. The melatonin analogs are unique inasmuch as they can also enhance daytime alertness. The recently introduced melatonergic antidepressant agomelatine, which has established its supremacy over other antidepressants in having a significant chronobiologic activity, represents a good choice for treating depressive symptoms that are associated with jet lag.