Medical Studies on Melatonin – Sleep
Modern science recognises more than 100 diseases related to sleep, because sleep disorders that are left undiagnosed or untreated can result in drastic consequences for health. Experts estimate that roughly one in ten suffers from some kind of sleep disorder. This proportion is even higher among older people, with around 60 to 70 per cent of people over the age of 65 suffering from sleep disorders to differing extents. A sleep disorder is defined as such if a person sleeps for less than six hours a night in three out of seven nights over a period of six months.
Sleep deprivation and its health consequences
Studies have been finding for years that people who sleep too little or have to sleep at the wrong times, for example, suffer from flu-like infections four times as often, as their immune system is weakened as a result of the sleep deprivation. People who have been working shifts for more than 10 years are at particular risk; the WHO (World Health Organisation) has classified night shift work as carcinogenic. The risk of breast cancer can increase by up to 65 per cent, while the risk of intestinal and prostate cancer also rises drastically.
The likelihood of digestive system disorders, heart attack, stroke, diabetes, vascular diseases, and also cancer, dementia and obesity is also increased many times over. A lack of sleep can also result in impaired memory, lack of drive and mood swings. In the worst cases, this may result in hallucinations or depression.
Melatonin as a key hormone
The benefits of melatonin in regulating and optimising the sleep/wake cycle have long been proven. Especially as a chronotherapeutic drug, its value has been very successfully proven, providing support in mitigating the risk of one of the aforementioned diseases. And it has also been demonstrated that melatonin is highly tolerable over a longer period time, even at higher dosages. There is also no risk of addiction and/or dependency.
Medical Studies on Melatonin – Sleep
Predictions of melatonin suppression during the early biological night and their implications for residential light exposures prior to sleeping
The magnitude of nocturnal melatonin suppression depends upon the spectrum, amount, and duration of light exposure. The functional relationship between melatonin suppression and the light spectrum and amount have been previously described. Only one duration-dependent parameter was needed to extend this functional relationship to predict nocturnal melatonin suppression during the early biological night from a variety of published studies.
Chronotype, circadian rhythms and mood.
Growing evidence shows a link between mood and chronotype. The majority of studies measure chronotype as a preference for morning/evening activities, rather than actual sleep behaviour (i.e. midsleep) or biological markers of sleep timing (e.g. dim light melatonin onset).
Clinical Impact of Melatonin on Breast Cancer Patients Undergoing Chemotherapy; Effects on Cognition, Sleep and Depressive Symptoms: A Randomized, Double-Blind, Placebo-Controlled Trial.
This randomized, double-blinded, placebo-controlled trial tested the hypothesis that 20mg of melatonin before and during the first cycle of adjuvant chemotherapy for breast cancer (ACBC) reduced the side effects associated with cognitive impairment.
Daily and seasonal mitochondrial protection: Unraveling common possible mechanisms involving vitamin D and melatonin.
From an evolutionary point of view, vitamin D and melatonin appeared very early and share functions related to defense mechanisms. In the current clinical setting, vitamin D is exclusively associated with phosphocalcic metabolism. Meanwhile, melatonin has chronobiological effects and influences the sleep-wake cycle.
Selective slow-wave sleep suppression affects glucose tolerance and melatonin secretion. The role of sleep architecture.
Our study aimed to assess the impact of one night of slow-wave sleep (SWS) suppression on glucose tolerance, and explore whether melatonin plays a role in glucose tolerance impairment after SWS suppression.
Virtual discovery of melatonin receptor ligands to modulate circadian rhythms.
The neuromodulator melatonin synchronizes circadian rhythms and related physiological functions via actions at two G protein-coupled receptors: MT1 and MT2.
Effectiveness of Complementary and Alternative Medicine Interventions for Sleep Quality in Adult Intensive Care Patients: A Systematic Review.
Pharmacological interventions for sleep (analgesic, sedative and hypnotic agents) can both disrupt and induce sleep and have many negative side effects within the intensive care population. The use of complementary and alternative medicine therapies to assist with sleep has been studied but given the variety of modalities and methodological limitations no reliable conclusions have been drawn.
Short Sleep Is Associated With Low Bone Mineral Density and Osteoporosis in the Women’s Health Initiative.
Short sleep duration, recognized as a public health epidemic, is associated with adverse health conditions, yet little is known about the association between sleep and bone health. We tested the associations of usual sleep behavior and bone mineral density (BMD) and osteoporosis.
Circadian rhythm and its association with birth and infant outcomes: research protocol of a prospective cohort study.
Circadian rhythm plays an important role as our internal body's clock that synchronizes behavior and physiology according to the external 24-h light-dark cycle. Past studies have associated disrupted circadian rhythm with higher risk of miscarriages, preterm birth and low birth weights. This paper described the protocol of a prospective cohort study which aims to determine the circadian rhythm in pregnant women, identify its association with maternal factors during pregnancy, gestational weight gain, birth and infant outcomes.
Night shift work, short sleep and obesity.
Obesity is associated with increased general mortality and comorbidities, it is multifactorial and some evidence has shown that sleep duration and shift work may be implicated in its pathogenesis.
The association between sleep chronotype and obesity among black and white participants of the Bogalusa Heart Study.
Research indicates that sleep duration and quality are inter-related factors that contribute to obesity, but few studies have focused on sleep chronotype, representing an individual's circadian proclivity, nor assessed these factors in racially diverse middle-aged samples.
Influence of Dietary Sources of Melatonin on Sleep Quality: A Review.
Sleep is an essential biological phenomenon, being a physiological and behavioral process necessary for quality of life. Melatonin is a circadian hormone produced at night by the pineal gland, regulated by the light/dark cycle, under the control of the suprachiasmatic nucleus. Melatonin is an indoleamine, synthesized from the essential amino acid tryptophan via serotonin. Melatonin is also found in plants, where it helps fight oxidative stress. To present a systematic review on the ability of food sources of melatonin to promote healthy sleep.
New awakenings: current understanding of sleep dysfunction and its treatment in Parkinson’s disease.
The non-motor features of Parkinson's disease (PD) are increasingly being recognised. This review deals with the spectrum of sleep disorders associated with PD, which have a multifactorial aetiology and can significantly have an impact on the quality of life of patients and their carers.
Impact of Sleep Disorder as a Risk Factor for Dementia in Men and Women.
Sleep is an essential physiological process, especially for proper brain function through the formation of new pathways and processing information and cognition. Therefore, when sleep is insufficient, this can result in pathophysiologic conditions.
Melatonin inhibits GABAergic neurons in the hypothalamus consistent with a reduction in wakefulness.
Although melatonin is necessary for circadian regulation of sleep, the mechanisms underlying this effect of melatonin are still unclear. In the present study, we showed that melatonin suppressed the activity of GABAergic neurons in the lateral hypothalamus, which has been reported to play a crucial role in maintaining wakefulness.
Effect of acute total sleep deprivation on plasma melatonin, cortisol and metabolite rhythms in females.
Disruption to sleep and circadian rhythms can impact on metabolism. The study aimed to investigate the effect of acute sleep deprivation on plasma melatonin, cortisol and metabolites, to increase understanding of the metabolic pathways involved in sleep/wake regulation processes.
Association Between Sleep Quality and Semen Parameters and Reproductive Hormones: A Cross-Sectional Study in Zhejiang, China.
The effects of sleep duration on semen quality have been documented in many epidemiological studies. However, the association between sleep quality and semen parameters and reproductive hormones is still unclear.
Poor sleep quality associates with self-reported psychiatric and cardiometabolic symptoms independently of sleep timing patterns in a large sample of rural and urban workers.
Poor sleep associates with mental and cardiometabolic pathological outcomes. The participation of sleep timing features in the pathways by which this relationship occurs is not clear.
Circadian insights into the biology of depression: Symptoms, treatments and animal models.
In depression, symptoms range from loss of motivation and energy to suicidal thoughts. Moreover, in depression alterations might be also observed in the sleep-wake cycle and in the daily rhythms of hormonal (e.g., cortisol, melatonin) secretion.
The Effects of Melatonin on the Descending Pain Inhibitory System and Neural Plasticity Markers in Breast Cancer Patients Receiving Chemotherapy: Randomized, Double-Blinded, Placebo-Controlled Trial.
Adjuvant chemotherapy for breast cancer (ACBC) has been associated with fatigue, pain, depressive symptoms, and disturbed sleep. And, previous studies in non-cancer patients showed that melatonin could improve the descending pain modulatory system (DPMS).
Reduced melatonin synthesis in pregnant night workers: Metabolic implications for offspring.
Several novel animal studies have shown that intrauterine metabolic programming can be modified in the event of reduced melatonin synthesis during pregnancy, leading to glucose intolerance and insulin resistance in the offspring. It is therefore postulated that female night workers when pregnant may expose the offspring to unwanted health threats.
Advanced melatonin onset relative to sleep in women with unmedicated major depressive disorder.
Studies on circadian timing in depression have produced variable results, with some investigations suggesting phase advances and others phase delays. This variability may be attributable to differences in participant diagnosis, medication use, and methodology between studies.
An integrated approach to diagnosing and managing sleep disorders in menopausal women.
Sleep disorders increase in prevalence during the menopausal transition and they constitute a complex phenomenon. Insomnia, the main sleep disorder, can be a primary disorder or it can be secondary to hot flushes (HF), mood disorders, psychosocial factors, medical conditions, and other sleep disturbances, such as obstructive sleep apnoea (OSA) or restless legs syndrome (RLS).
Sleep, premenstrual mood disorder, and women’s health.
Women experience increased vulnerability for both mood and sleep disorders, and the female menstrual cycle represents one fundamental mechanism related to risk.
Effects of light on human circadian rhythms, sleep and mood.
Humans live in a 24-hour environment, in which light and darkness follow a diurnal pattern. Our circadian pacemaker, the suprachiasmatic nuclei (SCN) in the hypothalamus, is entrained to the 24-hour solar day via a pathway from the retina and synchronises our internal biological rhythms.
The Circadian Syndrome: is the Metabolic Syndrome and much more!
The Metabolic Syndrome is a cluster of cardio-metabolic risk factors and comorbidities conveying high risk of both cardiovascular disease and type 2 diabetes. It is responsible for huge socio-economic costs with its resulting morbidity and mortality in most countries. The underlying aetiology of this clustering has been the subject of much debate.
Healthier rhythm, healthier brain? Integrity of circadian melatonin and temperature rhythms relates to the clinical state of brain-injured patients.
Healthy circadian rhythmicity has been suggested to relate to a better state of brain-injured patients and to support the emergence of consciousness in patient groups characterized by a relative instability thereof such as patients with disorders of consciousness (DOC).
Pineal gland abnormality in major depressive disorder.
Patients with major depressive disorder (MDD) often have circadian rhythm alteration and sleep disturbance. The pineal gland regulates the circadian rhythm and sleep by the secretion of melatonin neurohormone. However, the relationship between pineal abnormality and MDD remains elusive.
Night-shift work, circadian and melatonin pathway related genes and their interaction on breast cancer risk: evidence from a case-control study in Korean women.
Our purpose is to investigate the impact of circadian and melatonin pathway genes as well as their interactions with night-shift work (NSW) on breast cancer risk in Korean women.
Melatonin: Countering Chaotic Time Cues.
Last year melatonin was 60 years old, or at least its discovery was 60 years ago. The molecule itself may well be almost as old as life itself. So it is time to take yet another perspective on our understanding of its functions, effects and clinical uses.
New Insights Into the Circadian Rhythm and Its Related Diseases.
Circadian rhythms (CR) are a series of endogenous autonomous oscillators generated by the molecular circadian clock which acting on coordinating internal time with the external environment in a 24-h daily cycle.
Circadian Clock Genes in Diabetic Kidney Disease (DKD).
The purpose of this review is to provide a brief summary about the current state of knowledge regarding the circadian rhythm in the regulation of normal renal function.
Pregnancy Induces an Earlier Chronotype in Both Mice and Women.
Daily rhythms generated by endogenous circadian mechanisms and synchronized to the light-dark cycle have been implicated in the timing of birth in a wide variety of species. Although chronodisruption (e.g., shift work or clock gene mutations) is associated with poor reproductive outcomes, little is known about circadian timing during pregnancy.
Chronodisruption, Metabolic Homeostasis, and the Regulation of Inflammation in Adipose Tissues.
Molecular circadian clocks align daily behavioral and metabolic rhythms with the external day-night cycle. Priming energy metabolism for recurring changes on a 24-hour basis, these clocks are deeply interlinked with metabolic homeostasis and health.
Melatonin MT1 receptor as a novel target in neuropsychopharmacology: MT1 ligands, pathophysiological and therapeutic implications, and perspectives.
Melatonin (MLT), a neuromodulator mainly acting through two G-protein coupled receptors MT1 and MT2, regulates many brain functions, including circadian rhythms, mood, pain and sleep. MLT and non-selective MT1/MT2 receptor agonists are clinically used in neuropsychiatric and/or sleep disorders.
Effects of red light on sleep inertia.
Sleep inertia, broadly defined as decrements in performance and lowering of alertness following waking, lasts for durations ranging between 1 min and 3 hrs. This study investigated whether, compared to a dim light condition (the control), exposure to long-wavelength (red) light delivered to closed eyelids during sleep (red light mask) and to eyes open upon waking (red light goggles) reduced sleep inertia.
Melatonin profiles during the third trimester of pregnancy and health status in the offspring among day and night workers: A case series.
Successful pregnancy requires adaptation in maternal physiology. During intrauterine life the mother's circadian timing system supports successful birth and postnatal development. Maternal melatonin is important to transmit circadian timing and day length to the fetus.
Night workers have lower levels of antioxidant defenses and higher levels of oxidative stress damage when compared to day workers.
The effects of circadian misalignment and work shift on oxidative stress profile of shift workers have not been explored in the literature. The present study aimed to evaluate the role of shift work (day and night) and social jetlag - a measure of circadian misalignment - with oxidative stress markers.
Interplay between diet, exercise and the molecular circadian clock in orchestrating metabolic adaptations of adipose tissue.
Disruption of circadian rhythmicity induced by prolonged light exposure, altered sleep patterns and shift work is associated with the development of obesity and related metabolic disorders, including type 2 diabetes and cardiovascular diseases.
Insomnia as a predictor of mental disorders: A systematic review and meta-analysis.
Previous research has identified insomnia as a predictor for the onset of depression. The aim of this meta-analysis is to investigate whether insomnia also predicts the onset of other mental disorders.
Melatonin, the Hormone of Darkness: From Sleep Promotion to Ebola Treatment.
Melatonin is a hormone secreted by the enigmatic pineal gland in response to darkness, hence the name hormone of darkness. It has generated a great deal of interest as a therapeutic modality for various diseases particularly sleep disorders.
Clinical uses of melatonin: evaluation of human trials.
During the last 20 years, numerous clinical trials have examined the therapeutic usefulness of melatonin in different fields of medicine. The objective of this article is to review, in depth, the science regarding clinical trials performed to date.
The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia.
Objectives of this study were to investigate the effects of prolonged-release melatonin 2 mg (PRM) on sleep and subsequent daytime psychomotor performance in patients aged > or =55 years with primary insomnia, as defined by fourth revision of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association.
Melatonin, synthetic analogs, and the sleep/wake rhythm.
Melatonin, a widespread hormone in the animal kingdom, is produced by several organs and tissues besides the pineal gland. Whilst extrapineal melatonin behaves as a cytoprotective molecule, the pineal produces the hormone in a rhythmic manner. The discovery of melatonin in 1958, and the characterization of its synthesis somewhat later, let to the description of its photoperiodic regulation and its relationship with the biological rhythms such as the sleep/wake rhythm.
The effects of melatonin on sleep-wake rhythm of daytime haemodialysis patients: a randomized, placebo-controlled, cross-over study (EMSCAP study).
The aim of this study was to investigate the effects of exogenous melatonin on sleep-wake rhythm in haemodialysis patients.
Sleep duration, melatonin and breast cancer among Chinese women in Singapore.
Sleep duration has been hypothesized to be inversely associated with breast cancer risk, possibly due to greater overall melatonin production in longer sleepers. However, data are inconclusive from the three studies conducted in Western populations on sleep duration and breast cancer risk.
Role of the melatonin system in the control of sleep: therapeutic implications.
The circadian rhythm of pineal melatonin secretion, which is controlled by the suprachiasmatic nucleus (SCN), is reflective of mechanisms that are involved in the control of the sleep/wake cycle. Melatonin can influence sleep-promoting and sleep/wake rhythm-regulating actions through the specific activation of MT(1) (melatonin 1a) and MT(2) (melatonin 1b) receptors, the two major melatonin receptor subtypes found in mammals.
Melatonin receptors: role on sleep and circadian rhythm regulation.
The circadian release of the hormone melatonin is regulated by the suprachiasmatic nucleus (SCN), which feeds back into the nucleus to modulate sleep and circadian phase through activation of the MT(1) and/or MT(2) melatonin receptors.
Plasma melatonin rhythms in young and older humans during sleep, sleep deprivation, and wake.
To determine the effects of sleep and sleep deprivation on plasma melatonin concentrations in humans and whether these effects are age-dependent.
The effects of melatonin on tinnitus and sleep.
To determine if melatonin improves tinnitus and if this improvement is related to improvement in sleep.
Phase-dependent treatment of delayed sleep phase syndrome with melatonin.
Delayed sleep phase syndrome (DSPS) is a circadian-rhythm sleep disorder characterized by abnormally late sleep and wake times. Melatonin, taken in the evening, advances sleep and circadian phase in patients with DSPS. However, little is known about the most effective dose or time of administration. In the present study, we tested the effectiveness of melatonin to advance the timing of sleep and circadian phase in individuals with DSPS.
Add-on melatonin improves sleep behavior in children with epilepsy: randomized, double-blind, placebo-controlled trial.
This double-blind, randomized, placebo-controlled study in epileptic children, aged 3 to 12 years, evaluated the effect of add-on melatonin on the sleep behavior of these children on sodium valproate monotherapy using a parental questionnaire.
Melatonin in patients with reduced REM sleep duration: two randomized controlled trials.
Recent data suggest that melatonin may influence human physiology, including the sleep-wake cycle, in a time-dependent manner via the body's internal clock.
Double blind study of melatonin effects on the sleep-wake rhythm, cognitive and non-cognitive functions in Alzheimer type dementia.
Previously, we reported that morning bright light therapy improved sleep time and cognitive function in Alzheimer type of dementia.
Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treatment.
The objective of the present study was to assess the toxicology of melatonin (10 mg), administered for 28 days to 40 volunteers randomly assigned to groups receiving either melatonin (N = 30) or placebo (N = 10) in a double-blind fashion.
Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach.
Benzodiazepines are the most frequently used drug for the treatment of insomnia. Prolonged use of benzodiazepine therapy is not recommended. However, many patients, particularly older patients, have difficulties discontinuing therapy. Melatonin, a hormone that is produced at night by the pineal gland, promotes normal sleep in humans and augments sleep induction by benzodiazepine therapy.
Effects of night shift on plasma concentrations of melatonin, LH, FSH and prolactin, and menstrual irregularity.
To examine the effect of night shift on the ovarian function, 122 teachers, 67 office workers, 377 nurses, 133 factory workers and 67 barmaids were surveyed.