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Nutrients Sep 2021Sleep is an essential component of overall human health but is so tightly regulated that when disrupted can cause or worsen certain ailments. An important part of this... (Review)
Review
Sleep is an essential component of overall human health but is so tightly regulated that when disrupted can cause or worsen certain ailments. An important part of this process is the presence of the well-known hormone, melatonin. This compound assists in the governing of sleep and circadian rhythms. Previous studies have postulated that dysregulation of melatonin rhythms is the driving force behind sleep and circadian disorders. A computer-aided search spanning the years of 2015-2020 using the search terms melatonin, circadian rhythm, disorder yielded 52 full text articles that were analyzed. We explored the mechanisms behind melatonin dysregulation and how it affects various disorders. Additionally, we examined associated therapeutic treatments including bright light therapy (BLT) and exogenous forms of melatonin. We found that over the past 5 years, melatonin has not been widely investigated in clinical studies thus there remains large gaps in its potential utilization as a therapy.
Topics: Animals; Biosynthetic Pathways; Circadian Rhythm; Humans; Light; Melatonin; Transcription, Genetic
PubMed: 34684482
DOI: 10.3390/nu13103480 -
Neurologia Sep 2022Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in... (Review)
Review
Melatonin is the main hormone involved in the control of the sleep-wake cycle. It is easily synthesisable and can be administered orally, which has led to interest in its use as a treatment for insomnia. Moreover, as production of the hormone decreases with age, in inverse correlation with the frequency of poor sleep quality, it has been suggested that melatonin deficit is at least partly responsible for sleep disorders. Treating this age-related deficit would therefore appear to be a natural way of restoring sleep quality, which is lost as patients age. However, despite the undeniable theoretical appeal of this approach to insomnia, little scientific evidence is available that supports any benefit of this substitutive therapy. Furthermore, the most suitable dose ranges and pharmaceutical preparations for melatonin administration are yet to be clearly defined. This review addresses the physiology of melatonin, the different pharmaceutical preparations, and data on its clinical usefulness.
Topics: Humans; Melatonin; Pharmaceutical Preparations; Sleep; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders
PubMed: 36064286
DOI: 10.1016/j.nrleng.2018.08.004 -
Nutrients Sep 2022Melatonin has become a popular dietary supplement, most known as a chronobiotic, and for establishing healthy sleep. Research over the last decade into cancer,... (Review)
Review
Melatonin has become a popular dietary supplement, most known as a chronobiotic, and for establishing healthy sleep. Research over the last decade into cancer, Alzheimer's disease, multiple sclerosis, fertility, PCOS, and many other conditions, combined with the COVID-19 pandemic, has led to greater awareness of melatonin because of its ability to act as a potent antioxidant, immune-active agent, and mitochondrial regulator. There are distinct similarities between melatonin and vitamin D in the depth and breadth of their impact on health. Both act as hormones, affect multiple systems through their immune-modulating, anti-inflammatory functions, are found in the skin, and are responsive to sunlight and darkness. In fact, there may be similarities between the widespread concern about vitamin D deficiency as a "sunlight deficiency" and reduced melatonin secretion as a result of "darkness deficiency" from overexposure to artificial blue light. The trend toward greater use of melatonin supplements has resulted in concern about its safety, especially higher doses, long-term use, and application in certain populations (e.g., children). This review aims to evaluate the recent data on melatonin's mechanisms, its clinical uses beyond sleep, safety concerns, and a thorough summary of therapeutic considerations concerning dietary supplementation, including the different formats available (animal, synthetic, and phytomelatonin), dosing, timing, contraindications, and nutrient combinations.
Topics: Animals; Antioxidants; COVID-19; Circadian Rhythm; Dietary Supplements; Humans; Melatonin; Pandemics; Vitamin D; Vitamins
PubMed: 36235587
DOI: 10.3390/nu14193934 -
Current Neuropharmacology Apr 2017Melatonin synchronizes central but also peripheral oscillators (fetal adrenal gland, pancreas, liver, kidney, heart, lung, fat, gut, etc.), allowing temporal... (Review)
Review
BACKGROUND
Melatonin synchronizes central but also peripheral oscillators (fetal adrenal gland, pancreas, liver, kidney, heart, lung, fat, gut, etc.), allowing temporal organization of biological functions through circadian rhythms (24-hour cycles) in relation to periodic environmental changes and therefore adaptation of the individual to his/her internal and external environment. Measures of melatonin are considered the best peripheral indices of human circadian timing based on an internal 24-hour clock.
METHODS
First, the pharmacology of melatonin (biosynthesis and circadian rhythms, pharmacokinetics and mechanisms of action) is described, allowing a better understanding of the short and long term effects of melatonin following its immediate or prolonged release. Then, research related to the physiological effects of melatonin is reviewed.
RESULTS
The physiological effects of melatonin are various and include detoxification of free radicals and antioxidant actions, bone formation and protection, reproduction, and cardiovascular, immune or body mass regulation. Also, protective and therapeutic effects of melatonin are reported, especially with regard to brain or gastrointestinal protection, psychiatric disorders, cardiovascular diseases and oncostatic effects.
CONCLUSION
This review highlights the high number and diversity of major melatonin effects and opens important perspectives for measuring melatonin as a biomarker (biomarker of early identification of certain disorders and also biomarker of their follow-up) and using melatonin with clinical preventive and therapeutic applications in newborns, children and adults based on its physiological regulatory effects.
Topics: Animals; Antioxidants; Brain; Circadian Rhythm; Humans; Melatonin; Mental Disorders
PubMed: 28503116
DOI: 10.2174/1570159X14666161228122115 -
Journal of Translational Medicine Mar 2019There are no guidelines concerning the best approach to improving sleep, but it has been shown that it can benefit the affected children and their entire families. The... (Review)
Review
BACKGROUND
There are no guidelines concerning the best approach to improving sleep, but it has been shown that it can benefit the affected children and their entire families. The aim of this review is to analyse the efficacy and safety of melatonin in treating pediatric insomnia and sleep disturbances.
MAIN BODY
Sleep disturbances are highly prevalent in children and, without appropriate treatment, can become chronic and last for many years; however, distinguishing sleep disturbances from normal age-related changes can be a challenge for physicians and may delay treatment. Some published studies have shown that melatonin can be safe and effective not only in the case of primary sleep disorders, but also for sleep disorders associated with various neurological conditions. However, there is still uncertainty concerning dosing regimens and a lack of other data. The dose of melatonin should therefore be individualised on the basis of multiple factors, including the severity and type of sleep problem and the associated neurological pathology.
CONCLUSIONS
Melatonin can be safe and effective in treating both primary sleep disorders and the sleep disorders associated with various neurological conditions. However, there is a need for further studies aimed at identifying the sleep disordered infants and children who will benefit most from melatonin treatment, and determining appropriate doses based on the severity and type of disorder.
Topics: Child; Child Behavior; Humans; Melatonin; Mental Disorders; Neurodevelopmental Disorders; Sleep Wake Disorders
PubMed: 30871585
DOI: 10.1186/s12967-019-1835-1 -
Biomolecules Aug 2020There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis,... (Review)
Review
There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis, with great impact in the peripartum period and adult life. Melatonin promotes adaptation through allostasis and stands out as an endogenous, dietary, and therapeutic molecule with important health benefits. The anti-inflammatory and antioxidant effects of melatonin are intertwined and are exerted throughout pregnancy and later during development and aging. Melatonin supplementation during pregnancy can reduce ischemia-induced oxidative damage in the fetal brain, increase offspring survival in inflammatory states, and reduce blood pressure in the adult offspring. In adulthood, disturbances in melatonin production negatively impact the progression of cardiovascular risk factors and promote cardiovascular and neurodegenerative diseases. The most studied cardiovascular effects of melatonin are linked to hypertension and myocardial ischemia/reperfusion injury, while the most promising ones are linked to regaining control of metabolic syndrome components. In addition, there might be an emerging role for melatonin as an adjuvant in treating coronavirus disease 2019 (COVID 19). The present review summarizes and comments on important data regarding the roles exerted by melatonin in homeostasis and oxidative stress and inflammation related pathologies.
Topics: Adjuvants, Pharmaceutic; Animals; Anti-Inflammatory Agents; Antioxidants; COVID-19; Coronavirus Infections; Homeostasis; Humans; Melatonin; Pandemics; Pneumonia, Viral
PubMed: 32825327
DOI: 10.3390/biom10091211 -
British Journal of Pharmacology Aug 2018In mammals, a central circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, tunes the innate circadian physiological rhythms to the ambient... (Review)
Review
In mammals, a central circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, tunes the innate circadian physiological rhythms to the ambient 24 h light-dark cycle to invigorate and optimize the internal temporal order. The SCN-activated, light-inhibited production of melatonin conveys the message of darkness to the clock and induces night-state physiological functions, for example, sleep/wake blood pressure and metabolism. Clinically meaningful effects of melatonin treatment have been demonstrated in placebo-controlled trials in humans, particularly in disorders associated with diminished or misaligned melatonin rhythms, for example, circadian rhythm-related sleep disorders, jet lag and shift work, insomnia in children with neurodevelopmental disorders, poor (non-restorative) sleep quality, non-dipping nocturnal blood pressure (nocturnal hypertension) and Alzheimer's disease (AD). The diminished production of melatonin at the very early stages of AD, the role of melatonin in the restorative value of sleep (perceived sleep quality) and its sleep-anticipating effects resulting in attenuated activation of certain brain networks are gaining a new perspective as the role of poor sleep quality in the build-up of β amyloid, particularly in the precuneus, is unravelled. As a result of the recently discovered relationship between circadian clock, sleep and neurodegeneration, new prospects of using melatonin for early intervention, to promote healthy physical and mental ageing, are of prime interest in view of the emerging link to the aetiology of Alzheimer's disease. LINKED ARTICLES: This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc.
Topics: Animals; Cardiovascular Diseases; Circadian Rhythm; Humans; Melatonin; Nervous System Diseases; Sleep; Sleep Wake Disorders
PubMed: 29318587
DOI: 10.1111/bph.14116 -
American Family Physician Jul 2017Insomnia accounts for more than 5.5 million visits to family physicians each year. Although behavioral interventions are the mainstay of treatment, pharmacologic therapy... (Review)
Review
Insomnia accounts for more than 5.5 million visits to family physicians each year. Although behavioral interventions are the mainstay of treatment, pharmacologic therapy may be necessary for some patients. Understanding the risks and benefits of insomnia medications is critical. Controlled-release melatonin and doxepin are recommended as first-line agents in older adults; the so-called z-drugs (zolpidem, eszopiclone, and zaleplon) should be reserved for use if the first-line agents are ineffective. For the general population with difficulty falling asleep, controlled-release melatonin and the z-drugs can be considered. For those who have difficulty staying asleep, low-dose doxepin and the z-drugs should be considered. Benzodiazepines are not recommended because of their high abuse potential and the availability of better alternatives. Although the orexin receptor antagonist suvorexant appears to be relatively effective, it is no more effective than the z-drugs and much more expensive. Sedating antihistamines, antiepileptics, and atypical antipsychotics are not recommended unless they are used primarily to treat another condition. Persons with sleep apnea or chronic lung disease with nocturnal hypoxia should be evaluated by a sleep specialist before sedating medications are prescribed.
Topics: Benzodiazepines; Doxepin; Humans; Hypnotics and Sedatives; Melatonin; Sleep Initiation and Maintenance Disorders
PubMed: 28671376
DOI: No ID Found -
Physiology (Bethesda, Md.) Sep 2014Melatonin is a small, highly conserved indole with numerous receptor-mediated and receptor-independent actions. Receptor-dependent functions include circadian rhythm... (Review)
Review
Melatonin is a small, highly conserved indole with numerous receptor-mediated and receptor-independent actions. Receptor-dependent functions include circadian rhythm regulation, sleep, and cancer inhibition. The receptor-independent actions relate to melatonin's ability to function in the detoxification of free radicals, thereby protecting critical molecules from the destructive effects of oxidative stress under conditions of ischemia/reperfusion injury (stroke, heart attack), ionizing radiation, and drug toxicity, among others. Melatonin has numerous applications in physiology and medicine.
Topics: Animals; Circadian Rhythm; Free Radicals; Humans; Melatonin; Oxidative Stress; Signal Transduction; Treatment Outcome
PubMed: 25180262
DOI: 10.1152/physiol.00011.2014 -
Journal of Sleep Research Dec 2023Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and... (Review)
Review
Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).
Topics: Adult; Humans; Sleep Initiation and Maintenance Disorders; Melatonin; Sleep; Benzodiazepines; Antidepressive Agents
PubMed: 38016484
DOI: 10.1111/jsr.14035