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Frontiers in Psychiatry 2021Sleep disorders (SLD) are supposed to be associated with increased risk and development of Alzheimer's disease (AD), and patients with AD are more likely to show SLD....
Sleep disorders (SLD) are supposed to be associated with increased risk and development of Alzheimer's disease (AD), and patients with AD are more likely to show SLD. However, neurobiological performance of patients with both AD and SLD in previous studies is inconsistent, and identifying specific patterns of the brain functional network and structural characteristics in this kind of comorbidity is warranted for understanding how AD and SLD symptoms interact with each other as well as finding effective clinical intervention. Thus, the aims of this systematic review were to summarize the relevant findings and their limitations and provide future research directions. A systematic search on brain functional and structural changes in patients with both AD and SLD was conducted from PubMed, Web of Science, and EMBASE databases. Nine original articles published between 2009 and 2021 were included with a total of 328 patients with comorbid AD and SLD, 367 patients with only AD, and 294 healthy controls. One single-photon emission computed tomography study and one multislice spiral computed tomography perfusion imaging study investigated changes of cerebral blood flow; four structural magnetic resonance imaging (MRI) studies investigated brain structural changes, two of them used whole brain analysis, and another two used regions of interest; two resting-state functional MRI studies investigated brain functional changes, and one 2-deoxy-2-(18F)fluoro-d-glucose positron emission tomography (18F-FDG-PET) investigated 18F-FDG-PET uptake in patients with comorbid AD and SLD. Findings were inconsistent, ranging from default mode network to sensorimotor cortex, hippocampus, brain stem, and pineal gland, which may be due to different imaging techniques, measurements of sleep disorder and subtypes of AD and SLD. Our review provides a systematic summary and promising implication of specific neuroimaging dysfunction underlying co-occurrence of AD and SLD. However, limited and inconsistent findings still restrict its neurobiological explanation. Further studies should use unified standards and comprehensive brain indices to investigate the pathophysiological basis of interaction between AD and SLD symptoms in the development of the disease spectrums.
PubMed: 34790139
DOI: 10.3389/fpsyt.2021.772068 -
Cureus May 2020Melatonin is a hormone produced by the pineal gland and is available over the counter for treating sleep problems in the pediatric population. We conducted a systematic... (Review)
Review
Melatonin is a hormone produced by the pineal gland and is available over the counter for treating sleep problems in the pediatric population. We conducted a systematic review of randomized clinical trials (RCTs) on MEDLINE and included six studies that met our inclusion criteria. RCTs were conducted in patients from two to 18 years of age with a diagnostic and statistical manual of mental disorders (DSM)-IV diagnosis of autism spectrum disease (ASD) and/or attention-deficit hyperactivity disorder (ADHD) in both short-term and long-term RCTs ranging from eight-week to 52-week studies. The mean difference in the children's sleep disorder showed statistically significant improvement in sleep duration and sleep latency onset compared to the placebo. Overall, a high response rate was observed in the melatonin group compared to the placebo in treating sleep problems in children. Melatonin is a well-tolerated and safe medication in the dose range of 2-10 mg/day in the child and adolescent population.
PubMed: 32617211
DOI: 10.7759/cureus.8335 -
Frontiers in Endocrinology 2022Diabetes-induced reproductive complications can lead to subfertility and infertility, raising the need to protect reproductive organs. There are limited medications used...
BACKGROUND
Diabetes-induced reproductive complications can lead to subfertility and infertility, raising the need to protect reproductive organs. There are limited medications used to improve reproductive health in diabetic patients. Melatonin, mainly produced by the pineal gland, may improve diabetes-associated reproductive complications through various mechanisms and may be a preferred candidate to protect the reproductive system. The present review aims to elucidate the underlying mechanisms of melatonin's effect on the reproductive system adversely affected by diabetes mellitus (DM).
METHODS
A comprehensive systematic literature electronic search was done using the PRISMA guidelines. Web of Science, PubMed, Embase, and Scopus were searched for publications up to June 2022. Search terms were selected based on the study purpose and were explored in titles and abstracts. After screening, out of a total of 169 articles, 14 pertinent articles were included based on our inclusion and exclusion criteria.
RESULTS
The results of studies using rats and mice suggest that DM adversely affects reproductive tissues, including testes and epididymis, prostate, corpus cavernosum, and ovary leading to alterations in histological and biochemical parameters compared to the normal groups. Treatment with melatonin improves oxidative stress, blocks apoptosis induced by endoplasmic reticulum stress and caspase activation, reduces pro-inflammation cytokines, and enhances steroidogenesis.
CONCLUSION
Melatonin exerted a protective action on the impaired reproductive system in and models of DM. The topic has to be followed up in human pregnancy cases that will need more time to be collected and approved.
Topics: Male; Female; Humans; Rats; Mice; Animals; Melatonin; Oxidative Stress; Antioxidants; Reproduction; Diabetes Mellitus
PubMed: 36303864
DOI: 10.3389/fendo.2022.1022989 -
Medicine Jan 2019Melatonin is the "clock factor" generated from pineal gland dominating regular circadian rhythm in humans. Migraine is one of the most severe and debilitating primary...
BACKGROUND
Melatonin is the "clock factor" generated from pineal gland dominating regular circadian rhythm in humans. Migraine is one of the most severe and debilitating primary headache disorders. Thus far, many diseases have been found to associate with melatonin, including the migraine. Therefore, melatonin's therapeutic potential for migraine is drawing attention.
OBJECTIVES
The aim of this study is to offer a systematic review of extant data of melatonin in migraine prophylaxis and to provide clinical implications and specific recommendations for future studies.
DATA SOURCES AND STUDY METHODS
A systematic research was conducted in September 2018 by using PubMed and Google Scholar databases to search for science literature published after 1988.
RESULTS
In all, 7 eligible articles were identified, including 4 randomized controlled studies and 3 observational studies. Due to high heterogeneities and limited number of studies, meta-analysis was not feasible, and only systematic review was performed. The results show that present evidence cannot claim melatonin's effectiveness according to the conflicting outcomes; however, the two negative outcomes of melatonin not different from placebo and melatonin inferior to amitriptyline are possible under-powering because of methodological, pharmacological, and therapeutic shortcomings. Observational studies also support melatonin's efficacy in migraine. As a result, melatonin is very likely to benefit migraine in prophylaxis and may have a similar effectiveness to other main preventive medications. Immediate-release melatonin 3 mg was established as effective, melatonin receptor agonist (Agomelatine) 25 mg and prolonged-release melatonin 4 mg were observed efficacious in observational studies. Melatonin displayed ineffective in the 2-month trial; thus, 3 months or more may be an enough duration for migraine therapy. Despite melatonin being generally safe, emerging literature is illustrating that a few severe adverse effects can be caused by melatonin, for example, liver injuries, reproductive system dysfunctions, and detrimental immunostimulation.
CONCLUSIONS
Melatonin is very likely to be a promising alternative for migraine prophylaxis. Current literature examining melatonin's efficacy in migraine prevention is growing, but still limited. Future studies of perfect design in methodology, pharmacology, and therapeutics are needed to achieve a deeper awareness of melatonin's role in migraine as well as more studies to explore the safety issues of melatonin medicine.
Topics: Central Nervous System Depressants; Humans; Melatonin; Migraine Disorders; Observational Studies as Topic; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Tension-Type Headache
PubMed: 30653130
DOI: 10.1097/MD.0000000000014099 -
Minerva Medica Apr 2024Melatonin, a hormone produced by the pineal gland, regulates the sleep-wake cycle and is effective in restoring biological rhythms. Prolonged-release melatonin (PRM) is...
INTRODUCTION
Melatonin, a hormone produced by the pineal gland, regulates the sleep-wake cycle and is effective in restoring biological rhythms. Prolonged-release melatonin (PRM) is designed to mimic the natural physiological pattern of melatonin release. In circadian medicine, PRM can be used to treat sleep and circadian rhythm disorders, as well as numerous organic diseases associated with sleep disorders.
EVIDENCE ACQUISITION
This systematic review analyzed 62 studies and adhered to the PRISMA guidelines, examining the effectiveness of PRM in organic pathologies and mental disorders.
EVIDENCE SYNTHESIS
The main evidence concerns primary insomnia in subjects over the age of 55, showing significant improvements in sleep quality. In neurodevelopmental disorders, there is evidence of a positive impact on sleep quality and quality of life for patients and their caregivers. PRM shows efficacy in the treatment of sleep disorders in mood disorders, schizophrenia, and neurocognitive disorders, but requires further confirmation. The additional use of PRM is supported for the withdrawal of chronic benzodiazepine therapies. The tolerability and safety of PRM are excellent, with ample evidence supporting the absence of tolerance and dependence.
CONCLUSIONS
Overall, PRM in circadian medicine is an effective chronopharmaceutical for restoring the sleep-wake rhythm in patients with insomnia disorder. This efficacy may also extend to sleep disorders associated with mood, neurodevelopmental and neurocognitive disorders, suggesting a further potential role in insomnia associated with various organic diseases.
Topics: Melatonin; Humans; Delayed-Action Preparations; Sleep Initiation and Maintenance Disorders; Circadian Rhythm; Sleep Disorders, Circadian Rhythm; Neurodevelopmental Disorders; Mood Disorders; Sleep Wake Disorders; Sleep Quality; Neurocognitive Disorders
PubMed: 38713204
DOI: 10.23736/S0026-4806.24.09303-0 -
Archives of Physical Medicine and... Feb 2023To investigate the utility of melatonin supplementation as a treatment option for individuals with sleep disturbance after traumatic brain injury (TBI).
OBJECTIVE
To investigate the utility of melatonin supplementation as a treatment option for individuals with sleep disturbance after traumatic brain injury (TBI).
DATA SOURCES
A systematic search was conducted in 6 electronic databases (Medline, AMED, CINAHL, Embase, Scopus, and SPORTDiscus) from earliest records to April 2022.
STUDY SELECTION
Studies were eligible for inclusion if they met the following criteria: a) human participants with sleep disturbance after TBI, b) melatonin or melatonergic agent used as an intervention to treat sleep disturbance, and c) outcomes of melatonin administration reported. All TBI severity types (mild, moderate, and severe) were eligible. The initial search retrieved a total of 595 articles, with 9 studies meeting the eligibility criteria.
DATA EXTRACTION
Two reviewers independently extracted data from eligible studies and assessed methodological quality. Extracted data consisted of participant and injury characteristics, melatonin interventional properties, and sleep outcome. Methodological quality was assessed via the Downs and Black checklist.
DATA SYNTHESIS
A total of 251 participants with TBI-induced sleep disturbance (mean age range: 14.0-42.5 years) were included. Melatonin, Circadin (prolonged-release melatonin), or Ramelteon (melatonin receptor agonist) were administered. Dosages and intervention duration ranged from 2 to 10 mg and 3 to 12 weeks, respectively. Eight out of 9 studies reported positive outcomes after melatonin treatment. Significant improvements in subjective sleep quality, objective sleep efficiency, and total sleep time were found with melatonin. Reductions in self-reported fatigue, anxiety, and depressive symptoms were also observed with melatonin treatment. No serious adverse events were reported after melatonin administration.
CONCLUSION
Melatonin has good tolerability after short-term use and the potential to be a therapeutic agent for those with sleep disturbance after TBI. Melatonin was shown to be beneficial to sleep quality, sleep duration, and sleep efficiency. Additional clinically relevant outcomes of improved mental health suggest that melatonin use may be a promising treatment option for individuals experiencing co-occurring disorders of mood and sleep disturbance post-injury.
Topics: Adolescent; Adult; Humans; Young Adult; Anxiety; Brain Injuries, Traumatic; Melatonin; Sleep; Sleep Wake Disorders
PubMed: 36243124
DOI: 10.1016/j.apmr.2022.09.018 -
Journal of Cellular Physiology Jul 2022Hepatic fibrosis is a reversible response to either acute or chronic cellular injury from a wide variety of etiologies, characterized by excessive deposition of...
Hepatic fibrosis is a reversible response to either acute or chronic cellular injury from a wide variety of etiologies, characterized by excessive deposition of extracellular matrix resulting in liver dysfunction and cirrhosis. Melatonin (N-acetyl-5-methoxytryptamine), the main product secreted by the pineal gland, is a multitasking indolamine with important physiological functions such as anti-inflammatory and antioxidant actions, modulation of circadian rhythms, and immune system enhancement. Among the numerous biological activities of melatonin, its antifibrotic effects have received increasingly more attention. In this study, we performed a systematic review of publications of the last 10 years evaluating the mechanisms of action of melatonin against liver fibrosis. The study protocol was registered at PROSPERO (CRD42022304744). Literature research was performed employing PubMed, Scopus, and Web of Science (WOS) databases, and after screening, 29 articles were included. Results from the selected studies provided denoted the useful actions of melatonin on the development, progression, and evolution of liver fibrosis. Melatonin antifibrotic effects in the liver involved the reduction of profibrogenic markers and modulation of several cellular processes and molecular pathways, mainly acting as an antioxidant and anti-inflammatory agent. In addition, the indolamine influenced different molecular processes, such as hepatocyte apoptosis, modulation of autophagy and mitophagy, restoration of circadian rhythms, and modulation of microRNAs, among others. Although some limitations have been found regarding variability in the study design, the findings here summarized display the potential role of melatonin in ameliorating the development of liver fibrosis and its possible progression to liver cirrhosis and hepatocarcinoma.
Topics: Anti-Inflammatory Agents; Antioxidants; Humans; Liver Cirrhosis; Melatonin
PubMed: 35404472
DOI: 10.1002/jcp.30735 -
World Neurosurgery Apr 2024To assess the efficacy and surgical outcomes of the simultaneous single-trajectory endoscopic biopsy and third ventriculostomy (ETV) in pineal region tumors. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the efficacy and surgical outcomes of the simultaneous single-trajectory endoscopic biopsy and third ventriculostomy (ETV) in pineal region tumors.
METHODS
A systematic review and meta-analysis adhering to Cochrane Standards and PRISMA framework were conducted. PubMed, Embase, and Web Of Science databases were searched until December 2023. Outcomes included rate of histopathologic diagnosis success, ETV success, complications, required VPS, and mortality.
RESULTS
Seventeen studies (N = 388) met inclusion criteria. Histopathologic diagnosis success rate was 90% for general population (95% CI: 86%-95%; I = 42%) and 94% for pediatric patients (95% CI: 89%-98%; I = 19%). ETV Success rate was 93% (95% CI: 88%-97%; I = 60%). An estimated risk of postoperative ETV complications was found to be 16% for the general population (95% CI: 5%-28%; I = 90%) and 5% for pediatric patients (95% CI: 0%-13%; I = 51%). The risk of requiring VPS was estimated as 2% (95% CI: 0%-4%; I = 39%) and for the pediatric population it was 7% (95% CI: 0%-16%; I = 69%). Mortality risk was found to be 1% (95% CI: 0%-3%; I = 0%).
CONCLUSIONS
Simultaneous endoscopic biopsy and ETV demonstrated high diagnostic and therapeutic success rates. The procedure's safety profile, with low mortality and complications, supports its role in treating hydrocephalus associated to pineal region tumors. Subgroup analyses revealed higher diagnostic success rates and required VPS in the pediatric population, whilst it had lower complication rates.
Topics: Child; Humans; Ventriculostomy; Neuroendoscopy; Third Ventricle; Pinealoma; Biopsy; Postoperative Complications; Hydrocephalus; Brain Neoplasms; Pineal Gland; Treatment Outcome; Retrospective Studies
PubMed: 38340795
DOI: 10.1016/j.wneu.2024.02.015 -
Anti-cancer Agents in Medicinal... 2018This systematic review aims to elucidate the role of melatonin (N-acetyl-5-metoxy-tryptamine) (MLT) in the prevention and treatment of cancer. MLT is a pineal gland...
This systematic review aims to elucidate the role of melatonin (N-acetyl-5-metoxy-tryptamine) (MLT) in the prevention and treatment of cancer. MLT is a pineal gland secretory product, an evolutionarily highly conserved molecule; it is also an antioxidant and an impressive protector of mitochondrial bioenergetic activity. MLT is characterized by an ample range of activities, modulating the physiology and molecular biology of the cell. Its physiological functions relate principally to the interaction of G Protein-Coupled MT1 and MT2 trans-membrane receptors (GPCRs), a family of guanidine triphosphate binding proteins. MLT has been demonstrated to suppress the growth of various tumours both, in vivo and in vitro. In this review, we analyze in depth, the antioxidant activity of melatonin, aiming to illustrate the cancer treatment potential of the molecule, by limiting or reversing the changes occurring during cancer development and growth.
Topics: Animals; Antineoplastic Agents; Antioxidants; Humans; Melatonin; Neoplasms; Oxidative Stress; Receptors, Melatonin
PubMed: 29173185
DOI: 10.2174/1871520617666171121120223 -
Journal of Food Science Jan 2020Sleep is an essential biological phenomenon, being a physiological and behavioral process necessary for quality of life. Melatonin is a circadian hormone produced at...
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. A literature search was performed on the PubMed, Scopus, and ScienceDirect databases, including only randomized, placebo-controlled trials published in English between 2005 and 2019. The methodological quality of the trials was assessed by the Jadad scale. Of the 25 eligible articles, eight met the inclusion criteria. They addressed the intake of milk or cherry juice in children, adults, and elderly subjects and evaluated sleep quality by questionnaires, sleep diary, actigraphy, or polysomnography. The analysis of the studies presented limitations, including lack of homogeneity of treatment dosage and duration. Nonetheless, the results indicated that the consumption of milk and sour cherries, sources of melatonin, may improve sleep quality in humans. These results pointed out to the potential suitability of food sources of melatonin as adjuvants in the prevention and treatment of sleep disorders. Further studies are necessary to better ascertain the aspects relevant to their use.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Dietary Supplements; Female; Humans; Male; Melatonin; Middle Aged; Oxidative Stress; Quality of Life; Randomized Controlled Trials as Topic; Sleep; Sleep Wake Disorders; Young Adult
PubMed: 31856339
DOI: 10.1111/1750-3841.14952