Sleep-wake Cycle Research Articles

Changes in RBM47 expression based on the timing of melatonin administration and its effects on Nrf2 activity in the hippocampus

Melatonin is an endogenous indoleamine that plays a significant role in various physiological processes, including the sleep-wake cycle, anxiety, immunity, and circadian rhythms. However, it is important to clarify that melatonin does not directly control circadian rhythms. Circadian rhythms are primarily synchronized by light, which acts on the suprachiasmatic nucleus (SCN) and subsequently regulates melatonin production. This light-mediated synchronization of circadian rhythms is essential for maintaining the alignment of the body with the light-dark cycle. In this study, we investigated the efficacy of melatonin administration during different times of the day or night and explored its neuroprotective effects. Furthermore, we aimed to apply these findings to rodent models of dementia, aging, and neuro-inflammation for potential therapeutic applications. Our study uncovered novel evidence suggesting the involvement of RNA-binding motif protein (RBM)-47 and Nrf2 in the signaling pathways associated with melatonin administration during both day and night. We examined the role of RBM47 in Nrf2 activity through siRNA or CRISPR-mediated knockdown experiments using hippocampal neuronal cells and lentivirus injections in mice. In 5xFAD/aging/neuroinflammatory mouse models, antioxidant effects were enhanced when melatonin was administered during the day compared to nighttime administration. Furthermore, mRNA analysis and molecular biology experiments revealed the differential expression of RBM47 depending on the timing of melatonin administration. These findings suggest that a decrease in RBM47 expression may improve the antioxidant defense system in the hippocampus. Consequently, administering melatonin during the day rather than at night may present a plausible therapeutic strategy as an antioxidant.

Influence of nutrition and food on sleep-is there evidence?

The influence of sleep disorders on metabolism, especially concerning obesity and diabetes, as well as obesity and obstructive sleep apnea, has been widely investigated. However, the effect of nutrition and the intake of certain foods on sleep has only recently gained attention. In recent years, there have been publications on intake of certain foods and certain diets regarding their influence on sleep, as well as activity of adipocytes and their effect on production of sleep hormones. Following PRISMA guidelines, we performed a PubMed search using the key words "sleep," "sleep disorders," "nutrition," "food," and "food intake" published from 2012 to 2022. We excluded by consensus all articles with diets and exercise programs or bariatric surgery for weight loss to treat sleep apnea, all articles on connections between sleep disorders and metabolic disorders, and articles concerning the influence of drugs on neuroactive substances. Of the 4155 publications revealed, 988 had nutrition, metabolism, and sleep as the primary topic of research. Of these 988 publications, only 26 fulfilled the content requirements concerning the influence of certain food and diets on sleep or sleep disorders, including the influence of the gastrointestinal system and adipocytes on sleep hormones. None of the investigations revealed clear evidence of an effect of a certain diet or food on sleep. Epidemiologic surveys suggest that shortened or fragmented sleep and chronotype in adults influence nutrition and fat metabolism. Additionally, there is evidence that adipocyte signaling influences neuronal mediators and hormones of the sleep-wake cycle. There is no evidence of a direct influence of certain nutrition or food intake on sleep. Obesity via adipocyte signaling may influence the sleep-wake cycle, though the molecular research on this topic is based on animal studies.

Assessment of cognitive function and sleep-wake rhythms in community-dwelling older adults.

Disruption of the circadian rhythm and sleep-wake cycles is a consequence of aging and is associated with the cognitive decline and many neurodegenerative conditions. We investigated the bedtime, wake-up time, sleep timing (midpoint between bedtime and wake-up time), and sleep timing standard deviation (SD) using the actigraphy among 80 consecutive volunteers aged ≥ 60years. Global cognitive function and executive function of detailed cognitive domains were evaluated using the mini-mental state examination (MMSE) and Wisconsin card sorting test (WCST) and subjective daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). The category achievement (CA), total errors (TE), perseverative errors of Nelson (PEN), non-perseverative errors (NPE), and difficulties in maintaining set (DMS) on the WCST were significantly correlated with sleep timing SD (CA: r = - 0.276, p = 0.013, TE: r = 0.311, p = 0.005, PEN: r = 0.241, p = 0.032, NPE: r = 0.250, p = 0.025, DMS: r = 0.235, p = 0.036), but not with the MMSE score. Multiple regression analyses with the stepwise forward selection method including age, ESS score, bedtime, sleep timing, and sleep timing SD, revealed that the ESS score, and sleep timing SD were significant factors related to CA on the WCST (ESS score: β = - 0.322, p = 0.004; sleep timing SD: β = - 0.250, p = 0.022). Assessment of sleep-wake rhythms, daytime sleepiness, and cognitive function using the MMSE and WCST is valuable for the prediction of cognitive decline in the geriatric population.

Ketogenic Diet Affects Sleep Architecture in C57BL/6J Wild Type and Fragile X Mice.

Nearly half of children with fragile X syndrome experience sleep problems including trouble falling asleep and frequent nighttime awakenings. The goals here were to assess sleep-wake cycles in mice in response to Fmr1 genotype and a dietary intervention that reduces hyperactivity. Electroencephalography (EEG) results were compared with published rest-activity patterns to determine if actigraphy is a viable surrogate for sleep EEG. Specifically, sleep-wake patterns in adult wild type and Fmr1KO littermate mice were recorded after EEG electrode implantation and the recordings manually scored for vigilance states. The data indicated that Fmr1KO mice exhibited sleep-wake patterns similar to wild type littermates when maintained on a control purified ingredient diet. Treatment with a high-fat, low-carbohydrate ketogenic diet increased the percentage of non-rapid eye movement (NREM) sleep in both wild type and Fmr1KO mice during the dark cycle, which corresponded to decreased activity levels. Treatment with a ketogenic diet flattened diurnal sleep periodicity in both wild type and Fmr1KO mice. Differences in several sleep microstructure outcomes (number and length of sleep and wake bouts) supported the altered sleep states in response to a ketogenic diet and were correlated with altered rest-activity cycles. While actigraphy may be a less expensive, reduced labor surrogate for sleep EEG during the dark cycle, daytime resting in mice did not correlate with EEG sleep states.

Artificial light and neurodegeneration: does light pollution impact the development of Alzheimer's disease?

Two multidimensional problems of recent times - Alzheimer's disease and light pollution - seem to be more interrelated than previously expected. A series of studies in years explore the pathogenesis and the course of Alzheimer's disease, yet the mechanisms underlying this pathology remain not fully discovered and understood. Artificial lights which accompany civilization on a daily basis appear to have more detrimental effects on both environment and human health than previously anticipated. Circadian rhythm is affected by inappropriate lighting conditions in particular. The consequences are dysregulation of the sleep-wake cycle, gene expression, neuronal restructuring, brain's electricity, blood flow, metabolites' turnover, and gut microbiota as well. All these phenomena may contribute to neurodegeneration and consequently Alzheimer's disease. There is an increasing number of research underlining the complexity of the correlation between light pollution and Alzheimer's disease; however, additional studies to enhance the key tenets are required for a better understanding of this relationship.

Relação entre sono e memória: Mais próximos do que você imagina

Hypnology (the study of sleep) is an area of medicine that permeates all others, because sleep is a fundamental part of everyone's life, since we spend a third of it asleep. This is due to its circadian rhythm. For this to happen, the action of modulating neurons is fundamental, each with different neuromediators that send out axons, establishing synapses in large areas of the cerebral cortex and regions that extend from the thalamus to the spinal cord. In addition, there is an interaction between the organism and the environment that regulates the sleep-wake cycle more effectively. This interaction characterizes the timer systems, which have cells capable of detecting environmental variations - sensory cells, especially light variations, and the so-called oscillator cells or pacemakers, which are responsible for the cycle regardless of external influences. In addition, there are hormonal interactions that influence both the sleep-wake cycle and organic functions. It is essential to study these relationships in order to understand the different states and stages of sleep, namely: slow-wave sleep, also known as non-REM sleep, and fast-wave sleep or REM sleep. Non-REM sleep is further subdivided into 4 stages, in which the human being starts from wakefulness and plunges into the various stages of depth. REM sleep is the deepest sleep, the stage of dreams, in which it is more difficult to wake the individual. Numerous nerve circuits are formed in this last stage of sleep, and it is this stage that is partly responsible for memory consolidation. There are various types of memory: those acquired throughout life, whether conscious or not, are essential for human beings to live well in society and form their individuality. The storage and recall of memories depends on the emotions experienced by each person. This changes the storage process and the places where memories are stored in each person's brain. There are regions that are essential and common to everyone, such as the hippocampus and amygdala, but the place where long-term memories are stored depends on each person's reaction to a given situation, and this will happen during the REM sleep phase. Becoming aware of this topic is fundamental to understanding the importance of good sleep hygiene, which is essential for achieving a substantial improvement in sleep quality and, consequently, quality of life, whether in terms of mood, health, cognition, memory and its consequences, or aspects related to work or academicism.

Suprachiasmatic nucleus promotes hyperglycemia induced by sleep delay

Short sleep is linked to disturbances in glucose metabolism and may induce a prediabetic condition. The biological clock in the suprachiasmatic nucleus (SCN) regulates the glucose rhythm in the circulation and the sleep-wake cycle. SCN vasopressin neurons (SCNVP) control daily glycemia by regulating the entrance of glucose into the arcuate nucleus (ARC). Thus, we hypothesized that sleep delay may influence SCN neuronal activity. We, therefore, investigated the role of SCNVP when sleep is disrupted by forced locomotor activity. After 2h of sleep delay, rats exhibited decreased SCNVP neuronal activity, a decrease in the glucose transporter GLUT1 expression in tanycytes lining the third ventricle, lowered glucose entrance into the ARC, and developed hyperglycemia. The association between reduced SCNVP neuronal activity and hyperglycemia in sleep-delayed rats was evidenced by injecting intracerebroventricular vasopressin; this increased GLUT1 immunoreactivity in tanycytes, thus promoting normoglycemia. Following sleep recovery, glucose levels decreased, whereas SCNVP neuronal activity increased. These results imply that sleep-delay-induced changes in SCNVP activity lead to glycemic impairment, inferring that disruption of biological clock function might represent a critical step in developing type 2 diabetes.

Nonlinear relationship between sleep midpoint and depression symptoms: a cross-sectional study of US adults

BackgroundDespite the close relationship between sleep–wake cycles and depression symptoms, the relationship between sleep midpoint and depression symptoms in adults remains understudied.MethodsIn this cross-sectional study, 18280 adults aged ≥ 18 years from the National Health and Nutrition Examination Survey (NHANES) 2015–2020 were analyzed. Covariates included age, sex, race/ethnicity, education level, marital status, family income, body mass index, smoking status, drinking status, physical activity, comorbid condition, sleep duration, and sleep disturbance were adjusted in multivariate regression models.ResultsWeighted restricted cubic spline based on the complex sampling design of NHANES showed that in participants with a sleep midpoint from 2:18 AM to 6:30 AM, the prevalence of depression symptoms increased by 0.2 times (adjusted odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.08–1.33) per 1-h increment in sleep midpoint compared to the reference point of 2:18 AM. For participants with a sleep midpoint after 6:30 AM and before 2:18 AM the next day, the relationship between sleep midpoint and depression symptoms was not significant after adjusting for all covariates (adjusted OR = 1.01, 95% CI: 0.99–1.03).ConclusionsThe findings indicate a significant nonlinear association between sleep midpoint and depression symptoms in a nationally representative sample of adults.

Effect of melatonin on sleep quality and EEG features in childhood epilepsy: a possible non-conventional treatment.

Sleep and epilepsy are characterized by a bidirectional relationship. Indeed, epilepsy predisposes to the development of sleep disorders, while sleep deprivation may exacerbate epilepsy. In addition, antiseizure medication can disrupt normal sleep architecture. Therefore, adequate sleep hygiene could lead to improvement in seizure control. The present study aimed to evaluate the effect of melatonin on seizure frequency, EEG tracing, and sleep in children with focal idiopathic epilepsy. This observation study evaluated the effect of 4 mg oral melatonin in ameliorating sleep-wake cycle, seizure frequency, and EEG features in children with focal idiopathic epilepsy of infancy. Twenty children were enrolled from September 2020 to August 2021. The study consisted of serial controls at enrollment (t0), at 3 months (t1), and at 6 months (t2) including neurological examination, questionnaire about sleep disturbances (CSHQ), and EEG. A significant improvement in sleep quality and daytime sleepiness was observed after melatonin supplementation. Furthermore, we observed a noteworthy improvement in EEG tracing at t2 that exhibited a significant correlation with improvements in CSHQ scores. The studies conducted so far to evaluate the effect of melatonin in persons with epilepsy do not lead to definitive conclusions. Despite the small population sample and the study design, we report sleep and EEG improvement after melatonin administration in our cohort. Larger studies are needed to further study the neuroprotective and anticonvulsant properties of melatonin.

Differential responses to artificial photoperiods of the rising and falling phases of human melatonin rhythm are consistent with a dual oscillator hypothesis.

Circadian rhythms and sleep-wake cycles were measured in volunteers staying singly in temporal isolation unit where they were exposed to artificial short and long light-dark (LD) cycles for 7 days. The long day consisted of 16-h light and 8-h dark (LD 16:8) and the short day consisted of 8-h light and 16-h dark (LD 8:16). During the light period, bright light of approximately 5,000 lux was given from the ceiling and during the dark period there was no illumination. Sleep was monitored by bed sensors, wrist actiwatch, and polysomnography (PSG) on the first and last nights of the schedule. Sleep length was significantly longer under LD 8:16 than under LD 16:8 and the sleep quality estimated by PSG was worse under LD 8:16 than under LD 16:8, which were comparable to natural seasonality in sleep. The circadian rhythm in plasma melatonin was measured in dim light (10 lux) before and after the LD exposures. The nocturnal melatonin secretion (NMS) was significantly longer after LD 8:16 than after LD 16:8 due to differential phase shifts of the rising and falling phases of NMS. After LD 8:16, the falling phase was much advanced than the rising phase, whereas after LD 16:8 the rising phase was much delayed than the falling phase, resulting in the NMS compression. These results indicate that the light sensitivity in terms of phase shifting is different in the two circadian phases, supporting a dual oscillator hypothesis with different phase-response curves for light in the human circadian system.NEW & NOTEWORTHY The present study demonstrated differential light responsiveness of the rising and falling phases of nocturnal melatonin secretion in human subjects exposed to artificial long (LD 16:8) and short days (LD 8:16) and suggested the involvement of different oscillators under these phases. The findings well mimicked the seasonality of the circadian rhythms in nature and consisted with the evening/morning dual oscillator hypothesis proposed originally for nocturnal rodents, providing a new concept for the human circadian system.

Tuning the output of the higher plants Circadian Clock

The circadian clock is an ascribed regulator found in the cells of creatures, that keeps biological and behavioral processes in sync with daily environmental changes throughout two 24-hour cycles. When the circadian clock in humans malfunctions or is misaligned with environmental signals, the timing of the sleep-wake cycle is altered and several circadian rhythm sleep disorders result. Due to the Earth's rotation on its axis, predictable environmental changes are anticipated by complex processes. The combined term for these systems is the circadian clock. The circadian rhythm regulates photosynthesis, photoperiodism, and photoperiodism, making it the "primary controller of plant life." The circadian clock is made up of post-translational alterations to core oscillators, epigenetic tweaks to DNA and histones, and autoregulatory feedback loops in transcription. In addition, the circadian clock is cell-autonomous and regulates the circadian rhythms of distinct organs. Biochemical elements such as photosynthetic products, mineral nutrients, calcium ions, and hormones are used by the core oscillators to communicate with one another. Arabidopsis is utilized to identify clock-related genes that govern plant growth, germination, pollination, flowering, abiotic and biotic stress responses, and more. The biological cycles of all species, notably humans, are undoubtedly impacted by other elements, including high altitude and changing ecosystems, in addition to the ones already stated. Although it hasn't yet published any experimental or scientific evidence to support them, the implication that living things have lives does appear inescapable. Hence, the present study elaborates on the higher plants related to the circadian clock.

TRT – The Best Treatment for Balancing Testosterone in Middle Aged Men

Balance is critical to many aspects of life. Work-life balance ensures that we have time to enjoy the fruits of our labor. Hormones control bodily processes like – metabolism, homeostasis, growth and development, sexual function, reproduction, sleep-wake cycle, and mood. Most men see a gradual and progressive decline of testosterone, the primary male sex hormone, starting around age 30, at a rate of 1–2% per year, though in some men, the decline is faster than the body can adequately compensate. In these cases, the fallout can be felt throughout the body with symptoms that are both disruptive and inconvenient. It is produced in the testicles and the adrenal glands but regulated by the hypothalamic-pituitary-gonadal (HPG) axis, a feedback system that responds to circulating hormone levels. Hormonal imbalance in men closely parallels the aging process. The most effective way of balancing male hormones is using testosterone replacement therapy (TRT). Generally, a value < 300 ng/dL is considered low, leading to a condition called hypogonadism. While one-third of Indian men above 40 years of age suffer from hypogonadism, the proportion of them as appropriate candidates for testosterone therapy (TTh) is not clear, not only in India but also in most countries. TTh helps reverse the effects of hypogonadism, but it’s unclear if it would benefit otherwise healthy older men. Primary care physicians encounter clinical conditions of hormonal imbalances in males, such as precocious puberty, delayed puberty, and hypogonadism, in general practice, needing specialists’ consultation and guidance for their management. Quoting half a dozen case reports of hormonal imbalance and their management, this article provides the evidence to prescribe or not to prescribe hormones for men. Materials and Methods: Sample cases of precocious puberty, delayed puberty, male hypogonadism (MH) (general, diabetic, and intracranial hypertension), and a case of complication of TTh cases in adults and how they were diagnosed and managed. Literature review for current evidence for TTh in men globally and in Indian practices.

Exploring Astrocyte-Mediated Mechanisms in Sleep Disorders and Comorbidity.

Astrocytes, the most abundant cells in the brain, are integral to sleep regulation. In the context of a healthy neural environment, these glial cells exert a profound influence on the sleep-wake cycle, modulating both rapid eye movement (REM) and non-REM sleep phases. However, emerging literature underscores perturbations in astrocytic function as potential etiological factors in sleep disorders, either as protopathy or comorbidity. As known, sleep disorders significantly increase the risk of neurodegenerative, cardiovascular, metabolic, or psychiatric diseases. Meanwhile, sleep disorders are commonly screened as comorbidities in various neurodegenerative diseases, epilepsy, and others. Building on existing research that examines the role of astrocytes in sleep disorders, this review aims to elucidate the potential mechanisms by which astrocytes influence sleep regulation and contribute to sleep disorders in the varied settings of brain diseases. The review emphasizes the significance of astrocyte-mediated mechanisms in sleep disorders and their associated comorbidities, highlighting the need for further research.

Chronic jet lag reduces motivation and affects other mood-related behaviors in male mice.

Introduction: The circadian system regulates various physiological processes such as sleep-wake cycles, hormone secretion, metabolism, and the reaction to both natural and drug-based rewards. Chronic disruption of the circadian system caused by unsteady synchronization with light-dark (LD) schedules, such as advancing chronic jet lag (CJL), leads to adverse physiological effects and pathologies, and is linked with changes in mood and depressive behaviors in humans and rodent models. Methods: C57BL/6J male mice were subjected to circadian disruption through phase advances of 6h every 2days (CJL +6/2). Mice under 12:12-h LD cycle were used as controls. After 8weeks under these conditions, a battery of behavioral tests was performed to assess if mood-related behaviors were affected. Results: Compared to controls under 24h LD cycles, mice under CJL presented desynchronization of activity-rest rhythms that led to several behavioral impairments, including a decrease in motivation for food reward, and an increase in anxiety, anhedonia, and depressive-like behavior. Conclusion: Chronic circadian disruption, caused by an experimental CJL protocol, affects mood-related and reward-related behaviors in mice. Understanding the importance of the circadian system and its potential role for disruption due to CJL is important for maintaining good health and well-being.

Effects of chronic caffeine on patterns of brain blood flow and behavior throughout the sleep-wake cycle in freely behaving mice.

Caffeine has significant effects on neurovascular activity and behavior throughout the sleep-wake cycle. We used a minimally invasive microchip/video system to continuously record effects of caffeine in the drinking water of freely behaving mice. Chronic caffeine shifted both rest and active phases by up to 2 h relative to the light-dark cycle in a dose-dependent fashion. There was a particular delay in the onset of rapid eye movement (REM) sleep as compared with non-REM sleep during the rest phase. Chronic caffeine increased wakefulness during the active phase and consolidated sleep during the rest phase; overall, there was no net change in the amount of time spent in the wake, sleep, or REM sleep states during caffeine administration. Despite these effects on wakefulness and sleep, chronic caffeine decreased mean cerebral blood volume (CBV) during the active phase and increased mean CBV during the rest phase. Chronic caffeine also increased heart rate variability in both the sleep and wake states. These results provide new insight into the effects of caffeine on the biology of the sleep-wake cycle. Increased blood flow during sleep caused by chronic caffeine may have implications for its potential neuroprotective effects through vascular mechanisms of brain waste clearance.

Familiarity of Brazilian psychologists with basic concepts in sleep science and chronobiology

ABSTRACT Desynchronization of circadian rhythms and sleep-wake patterns impacts biochemical, physiological, and behavioral functions, including mental processes. The complex relationship between circadian rhythms and mental health makes it challenging to determine causality between circadian desynchronization and mental disorders. Regarding the fact that psychologists act as the front line for initial mental health care, we aimed to assess the knowledge and use of sleep science and basic chronobiology by professional psychologists in Brazil. Data were collected via an online questionnaire completed by 1384 professional psychologists between October 2018 and May 2019. Our findings revealed that ±80% of psychologists reported that at least half of their patients presented some sleep-related complaints; however, only ±27% routinely inquired about sleep quality even in the absence of patient complaints. Additionally, only ±66% initiated treatments to understand these complaints, potentially influenced by the lack of prior academic exposure to biological rhythms as reported by ±76% of Brazilian psychologists interviewed. Importantly, ±15% did not believe in an association between mental health and biological rhythms, and even a significant ±67% were unfamiliar with the term chronobiology and ±63% were not able to describe any other biological rhythm except for the sleep-wake cycle. These results demonstrate that fundamental concepts in chronobiology and sleep science are unknown to a substantial proportion of Brazilian psychologists. In conclusion, we propose that this subject could be more effectively integrated into psychologists’ academic training, potentially promoting benefits through the incorporation of a chronobiological approach in mental health practice.

Addressing Impaired Sleep Among Adults in the Psychiatric Care Setting

Insomnia is highly comorbid with mental disorders and commonly treated by mental health care clinicians. A review of literature provides evidence for shared pathophysiology in systems regulating arousal and sleep–wake cycles in insomnia, anxiety, and mood disorders. Evidence-based pharmacological treatment rationales, based on patterns of dysregulation, are presented. Sleep quality is essential to mental health, and early identification and treatment of insomnia can aid in recovery. [ Journal of Psychosocial Nursing and Mental Health Services, 61 (9), 6–9.]

The Role of Neuroglobin in the Sleep-Wake Cycle.

Neuroglobin (Ngb) is a protein expressed in the central and peripherical nervous systems of the vertebrate. The Ngb has different functions in neurons, including regulating O 2 homeostasis, oxidative stress, and as a neuroprotector after ischemia/hypoxia events. The Ngb is a hemoprotein of the globin family, structurally like myoglobin and hemoglobin. Ngb has higher expression in the cortex, hypothalamus, thalamus, brainstem, and cerebellum in mammals. Interestingly, Ngb immunoreactivity oscillates according to the sleep-wake cycle and decreases after 24 hours of sleep deprivation, suggesting that sleep homeostasis regulates Ngb expression. In addition, Ngb expresses in brain areas related to REM sleep regulation. Therefore, in the present review, we discuss the potential role of the Ngb in the sleep-wake regulation of mammals.

Effects of melatonin on the circadian functions of sleep-wake cycle, metabolism, hormonal regulation and immune activity: A recent review

Rhythms following a period of approximately 24 hours are called circadian (from Latin circa diem, approximately one day) rhythms. These rhythms are observed in the activities of various vital body functions. Melatonin is considered as an important molecule participating in the formation of circadian rhythms of virtually all organisms. As a molecular regulator of the circadian clock, melatonin has various regulatory functions in both physiological and pathological conditions. Sleep-wake cycle depends on CSF melatonin levels, and melatonin also has a protective effect on the disrupted sleep-wake cycle in various pathological conditions. Melatonin ensures the proper function of vital metabolic pathways; therefore, it improves metabolism-related systems and protects them from damage. A bidirectional relationship between hormonal activity and melatonin ensures it having a healing effect on various reproductive disorders. Finally, melatonin can target inflammation pathways and various elements of immune system by changing their behavior and structure. In summary, melatonin has important effects on vital body functions mediated by its receptors, signaling pathways and clock genes, and has the capacity to protect and improve these functions under pathological conditions.

The Effect of Melatonin on Body Weight and the Potential use of Melatonin as an Anti-Obesity Agent

Background: obesity is a major global health problem with more than 200 million obese men and almost 300 million obese women. Melatonin is a well-known molecule for its involvement in circadian rhythm regulation and has multiple pathological actions including control of appetite, sleep wake cycle and metabolic syndrome. Aim: to estimate the effect of melatonin supplements on obese patients on a calorie restricted diet in comparison to patients on lifestyle measures only in the form of weight loss, waist circumference and sleep quality. Subjects and Method: one hundred patients with body mass index > 24 were collected, fifty patients were started on melatonin 5 mg with calorie restricted diet and they were compared to fifty patients who were kept on lifestyle measures. After twelve weeks, patients were re-assessed for weight, waist circumference and sleep duration and quality and the development of any side effects. Data analyzed using paired t test. Results: patients’ group who were treated with melatonin has shown significant reduction in body weight (91.58. Vs 92.88, p value <0.0004) and waist circumference (99.36 +- 10.73 vs 101 +-10.51, p value< 0.0064). Patients treated with melatonin show improved insomnia severity index (5.47+-0.8 vs 9.08 +-3.58, p value <0.0001). 60% of patients noticed decreased appetite,35% reported daytime sleepiness and fatigue, 25% had dizziness and 20% had mild nausea. Conclusion: Melatonin significantly reduces the body weight, waist circumference and appetite more than placebo, it has been shown to be safe supplement and helpful in patients with sleep disturbance and obesity.