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Alzheimer's Research & Therapy Feb 2021The search for new Alzheimer's disease (AD) cerebrospinal fluid (CSF) and blood biomarkers with potential pathophysiological and clinical relevance continues, as new... (Review)
Review
BACKGROUND
The search for new Alzheimer's disease (AD) cerebrospinal fluid (CSF) and blood biomarkers with potential pathophysiological and clinical relevance continues, as new biomarkers might lead to improved early and differential diagnosis, monitoring of disease progression and might even identify new druggable targets. Melatonin might be an interesting biomarker as an inverse correlation between CSF melatonin levels, and severity of the neuropathology as measured by Braak stages has been described. Melatonin can be measured in different body fluids, such as CSF, blood, saliva and urine.
OBJECTIVES
The aim of this systematic review was to review all available studies regarding melatonin levels in different body fluids in the AD continuum and give an extensive overview of reported outcomes.
METHODS
We included papers comparing melatonin levels between healthy controls and human patients belonging to the AD continuum. A systematic search of PubMed and Web of Science led to inclusion of 20 full-length English papers following exclusion of duplicates.
RESULTS
This systematic literature search showed that disruptions in melatonin levels occur with age, but also in AD when compared to age-matched controls. Night-time melatonin levels were found to be lower in CSF and blood of AD patients as compared to controls. Literature was not conclusive regarding alterations in blood daytime melatonin levels or regarding saliva melatonin in AD patients. Decreased total and night-time melatonin production has been described in urine of AD patients.
CONCLUSION
Our systematic review shows evidence for disruptions in (night-time) melatonin levels in AD as compared to age-matched controls. Although more studies are needed to understand the contribution of disruption of the melatonergic system to the pathophysiology of AD, the potential anti-AD effects that have been attributed to melatonin, renders research on this topic relevant for the discovery of potential future treatment effects of melatonin for AD. The use of melatonin as potential blood biomarker for disease progression should also be further investigated.
Topics: Alzheimer Disease; Biomarkers; Diagnosis, Differential; Humans; Melatonin
PubMed: 33622399
DOI: 10.1186/s13195-021-00788-6 -
Anaesthesia Oct 2014We systematically reviewed randomised controlled trials of peri-operative melatonin. We included 24 studies of 1794 participants that reported eight peri-operative... (Meta-Analysis)
Meta-Analysis Review
We systematically reviewed randomised controlled trials of peri-operative melatonin. We included 24 studies of 1794 participants that reported eight peri-operative outcomes: anxiety; analgesia; sleep quality; oxidative stress; emergence behaviour; anaesthetic requirements; steal induction; and safety. Compared with placebo, melatonin reduced the standardised mean difference (95% CI) pre-operative anxiety score by 0.88 (0.44-1.33) and postoperative pain score by 1.06 (0.23-1.88). The magnitude of effect was unreliable due to substantial statistical heterogeneity, with I(2) 87% and 94%, respectively. Qualitative reviews suggested the melatonin improved sleep quality and emergence behaviour, and might be capable of reducing oxidative stress and anaesthetic requirements.
Topics: Anxiety; Humans; Melatonin; Pain, Postoperative; Perioperative Care; Randomized Controlled Trials as Topic; Sleep
PubMed: 24835540
DOI: 10.1111/anae.12717 -
Frontiers in Endocrinology 2023Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative... (Meta-Analysis)
Meta-Analysis
Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies.
BACKGROUND
Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin is an effective antioxidant agent that protects testicles against physical and toxic chemical stressors in animal models. This study aims to systematically review the melatonin's protective effects against anti-cancer stressors on rodential testicular tissue.
MATERIALS AND METHOD
An extensive search was conducted in Web of Science, Scopus, and PubMed for animal studies investigating exogenous melatonin's protective effects on rodent testicles exposed to anti-cancer chemicals and radiotherapeutic agents. Using the DerSimonian and Laird random-effect model, standardized mean differences and 95% confidence intervals were estimated from the pooled data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022355293).
RESULTS
The meta-analysis included 38 studies from 43 studies that were eligible for the review. Rats and mice were exposed to radiotherapy (ionizing radiations such as gamma- and roentgen radiation and radioactive iodine) or chemotherapy (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, and chlorambucil). According to our meta-analysis, all outcomes were significantly improved by melatonin therapy, including sperm quantity and quality (count, motility, viability, normal morphology, number of spermatogonia, Johnsen's testicular biopsy score, seminiferous tubular diameter, and seminiferous epithelial height), serum level of reproductive hormones (Follicle-Stimulating Hormone and testosterone), tissue markers of oxidative stress (testicular tissue malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, and total antioxidant capacity), and weight-related characteristics (absolute body, epididymis, testis, and relative testis to body weights). Most SYRCLE domains exhibited a high risk of bias in the included studies. Also, significant heterogeneity and small-study effects were detected.
CONCLUSION
In male rodents, melatonin therapy was related to improved testicular histopathology, reproductive hormones, testis and body weights, and reduced levels of oxidative markers in testicular tissues of male rodents. Future meticulous studies are recommended to provide a robust scientific backbone for human applications.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293, identifier CRD42022355293.
Topics: Humans; Male; Animals; Rats; Mice; Melatonin; Antioxidants; Iodine Radioisotopes; Semen; Thyroid Neoplasms; Oxidative Stress; Body Weight
PubMed: 37701901
DOI: 10.3389/fendo.2023.1184745 -
Cureus Nov 2023The gut microbiota is a community situated in the gastrointestinal tract that consists of bacteria thriving and contributing to the functions of our body. It is heavily... (Review)
Review
The gut microbiota is a community situated in the gastrointestinal tract that consists of bacteria thriving and contributing to the functions of our body. It is heavily influenced by what individuals eat, as the quality, amount, and frequency of food consumed can favor and inhibit specific bacteria. Type-2 diabetes mellitus (T2DM) is a common but detrimental condition that arises from excessive hyperglycemia, leading to either insulin resistance or damage to the B-cells that produce insulin in the pancreas. A poor diet high in sugar and fats leads to hyperglycemia, and as this persists, it can lead to the development of T2DM. Both insulin resistance and damage to B-cells are greatly affected by the diet an individual consumes, but is there a more involved relationship between the gut microbiota and T2DM? This paper aimed to evaluate the changes in the gut microbiota in patients with T2DM and the impacts of the changes in gut microbiota. and prevailed in patients with T2DM and healthy control, but their abundance varied greatly. There was also a significant decrease in bacteria like spp.and associated with insulin resistance. High levels of BMI in patients with T2DM have also been associated with increased levels of which has been associated with decreased fat metabolism and increased BMI. Metabolites such as butyrates and melatonin have also been identified as influencing the development and progression of T2DM. Testosterone levels have also been greatly influenced by the gut microbiota changes in T2DM, such that males with lower testosterone have a greater abundance of bacteria like and Identifying these changes and how they impact the body may lead to a treatment addressing insulin dysfunction and the changes that the altered gut microbiota leads to. Future research should address how treatment methods such as healthy diets, exercise, and anti-diabetics affect the gut microbiota and see if they influence sustained changes and reduced hyperglycemia.
PubMed: 38161953
DOI: 10.7759/cureus.49740 -
Systematic Reviews Mar 2023Pineal gland calcification is the formation of corpora arenacea predominantly composed of calcium and phosphorus. It plays an important role in regulating the light/dark... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pineal gland calcification is the formation of corpora arenacea predominantly composed of calcium and phosphorus. It plays an important role in regulating the light/dark circadian changes to synchronize their daily physiological activities like feeding, metabolism, reproduction, and sleep through the secretion of melatonin. Therefore, this study aimed to assess the pooled prevalence of pineal gland calcification.
METHODS
A systematic review was done using published research articles from different electronic databases. Cross-sectional studies were included for systematic review and only studies conducted on the human population were included for quantitative analysis. Published articles were selected by assessing the title and abstract for relevance to the review objectives. Finally, the full text was retrieved for further assessment.
RESULTS
The pooled prevalence of pineal gland calcification was 61.65% [95% CI: 52.81, 70.49], with a heterogeneity of I = 97.7%, P ≤ 0.001. According to the qualitative analysis, an increase in age, male sex, and white ethnicity are the major socio-demographic characteristics that increase the prevalence of pineal gland calcification.
CONCLUSION
The pooled prevalence of pineal gland calcification was higher compared with reports from previous studies. Different studies reported pineal gland calcification was most prevalent in the adult population compared with the pediatric age groups. According to the qualitative analysis, an increase in age, male sex, and white ethnicity are the major socio-demographic characteristics that increase the prevalence of pineal gland calcification.
Topics: Adult; Humans; Child; Male; Cross-Sectional Studies; Pineal Gland; Prevalence; Calcium; Databases, Factual
PubMed: 36879256
DOI: 10.1186/s13643-023-02205-5 -
Physical Activity and Nutrition Sep 2023Humans show near-24-h physiological and behavioral rhythms, which encompass the daily cycle of sleep and wakefulness. Exercise stimulates circadian rhythms, including...
PURPOSE
Humans show near-24-h physiological and behavioral rhythms, which encompass the daily cycle of sleep and wakefulness. Exercise stimulates circadian rhythms, including those of cortisol, melatonin, and core body temperature, and affects sleep quality. We systematically reviewed studies that examined the effects of exercise intensity and timing on physiological circadian rhythms and sleep quality.
METHODS
In this systematic review, we used the online databases PubMed, Science Direct, Web of Science, and Embase. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two independent and experienced systematic reviewers performed the search and selected relevant studies. The participant, intervention, comparison, and outcome characteristics were: (1) adults; (2) exercise treatment; (3) no exercise treatment or different types of exercise (pre-exercise baseline); (4) cortisol, melatonin, or core body temperature measurement, and subjective or objective sleep quality assessments.
RESULTS
We identified 9 relevant articles involving 201 participants (77.1% of whom were male). Our review revealed that short-term evening exercise delayed melatonin rhythm and increased nocturnal core body temperature; however, no negative effects on non-rapid eye movement sleep and sleep efficiency were observed. Moreover, no differences in sleep quality were observed between acute high-intensity and moderate-intensity exercises. With long exercise durations, the core body temperature tended to increase and return to baseline levels at 30-120 min.
CONCLUSION
Our review showed that short-term evening exercise and high-intensity exercise did not have a significant negative effect on sleep quality but physiological circadian rhythm tended to alter. Longterm morning exercise tended to decrease cortisol concentrations after awakening and improve sleep quality. Future studies should examine the effects of long-term exercise timing and intensity on circadian rhythm and sleep.
PubMed: 37946447
DOI: 10.20463/pan.2023.0029 -
BMC Anesthesiology Nov 2023Emergence agitation (EA) is a prevalent complication in children following general anesthesia. Several studies have assessed the relationship between melatonin or its... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Emergence agitation (EA) is a prevalent complication in children following general anesthesia. Several studies have assessed the relationship between melatonin or its analogs and the incidence of pediatric EA, yielding conflicting results. This meta-analysis aims to assess the effects of premedication with melatonin or its analogs on preventing EA in children after general anesthesia.
METHODS
PubMed, EMBASE, the Cochrane Library, ProQuest Dissertations & Theses Global, Web of Science, CNKI, Wanfang Data, clinicaltrials.gov, and WHO International Clinical Trials Registry Platform were searched until 25 November 2022. We included randomized controlled trials that assessed EA in patients less than 18 years old who underwent general anesthesia. We excluded studies that did not use a specific evaluation to assess EA.
RESULTS
Nine studies (951 participants) were included in this systematic review. Melatonin significantly reduced the incidence of EA compared with placebos (risk ratio 0.40, 95% CI 0.26 to 0.61, P < 0.01) and midazolam (risk ratio 0.48, 95% CI 0.32 to 0.73, P < 0.01). Dexmedetomidine remarkably decreased the incidence of EA compared with melatonin (risk ratio 2.04, 95% CI 1.11 to 3.73, P = 0.02).
CONCLUSIONS
Melatonin premedication significantly decreases the incidence of EA compared with placebos and midazolam. Dexmedetomidine premedication has a stronger effect than melatonin in preventing EA. Nevertheless, further studies are warranted to reinforce and validate the conclusion on the efficacy of melatonin premedication in mitigating EA in pediatric patients.
Topics: Child; Humans; Adolescent; Midazolam; Dexmedetomidine; Emergence Delirium; Melatonin; Sevoflurane; Methyl Ethers; Premedication
PubMed: 38037000
DOI: 10.1186/s12871-023-02356-x -
The Cochrane Database of Systematic... Feb 2018Fibromyalgia is a chronic widespread pain condition affecting millions of people worldwide. Current pharmacotherapies are often ineffective and poorly tolerated.... (Review)
Review
BACKGROUND
Fibromyalgia is a chronic widespread pain condition affecting millions of people worldwide. Current pharmacotherapies are often ineffective and poorly tolerated. Combining different agents could provide superior pain relief and possibly also fewer side effects.
OBJECTIVES
To assess the efficacy, safety, and tolerability of combination pharmacotherapy compared to monotherapy or placebo, or both, for the treatment of fibromyalgia pain in adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and Embase to September 2017. We also searched reference lists of other reviews and trials registries.
SELECTION CRITERIA
Double-blind, randomised controlled trials comparing combinations of two or more drugs to placebo or other comparators, or both, for the treatment of fibromyalgia pain.
DATA COLLECTION AND ANALYSIS
From all studies, we extracted data on: participant-reported pain relief of 30% or 50% or greater; patient global impression of clinical change (PGIC) much or very much improved or very much improved; any other pain-related outcome of improvement; withdrawals (lack of efficacy, adverse events), participants experiencing any adverse event, serious adverse events, and specific adverse events (e.g. somnolence and dizziness). The primary comparison was between combination and one or all single-agent comparators. We also assessed the evidence using GRADE and created a 'Summary of findings' table.
MAIN RESULTS
We identified 16 studies with 1474 participants. Three studies combined a non-steroidal anti-inflammatory drug (NSAID) with a benzodiazepine (306 participants); two combined amitriptyline with fluoxetine (89 participants); two combined amitriptyline with a different agent (92 participants); two combined melatonin with an antidepressant (164 participants); one combined carisoprodol, paracetamol (acetaminophen), and caffeine (58 participants); one combined tramadol and paracetamol (acetaminophen) (315 participants); one combined malic acid and magnesium (24 participants); one combined a monoamine oxidase inhibitor with 5-hydroxytryptophan (200 participants); and one combined pregabalin with duloxetine (41 participants). Six studies compared the combination of multiple agents with each component alone and with inactive placebo; three studies compared combination pharmacotherapy with each individual component but did not include an inactive placebo group; two studies compared the combination of two agents with only one of the agents alone; and three studies compared the combination of two or more agents only with inactive placebo.Heterogeneity among studies in terms of class of agents evaluated, specific combinations used, outcomes reported, and doses given prevented any meta-analysis. None of the combinations of drugs found provided sufficient data for analysis compared with placebo or other comparators for our preferred outcomes. We therefore provide a narrative description of results. There was no or inadequate evidence in any comparison for primary and secondary outcomes. Two studies only reported any primary outcomes of interest (patient-reported pain relief of 30%, or 50%, or greater). For each 'Risk of bias' item, only half or fewer of studies had unequivocal low risk of bias. Small size and selective reporting were common as high risk of bias.Our GRADE assessment was therefore very low for primary outcomes of pain relief of 30% or 50% or greater, PGIC much or very much improved or very much improved, any pain-related outcome, participants experiencing any adverse event, any serious adverse event, or withdrawing because of an adverse event.Three studies found some evidence that combination pharmacotherapy reduced pain compared to monotherapy; these trials tested three different combinations: melatonin and amitriptyline, fluoxetine and amitriptyline, and pregabalin and duloxetine. Adverse events experienced by participants were not serious, and where they were reported (in 12 out of 16 studies), all participants experienced them, regardless of treatment. Common adverse events were nausea, dizziness, somnolence, and headache.
AUTHORS' CONCLUSIONS
There are few, large, high-quality trials comparing combination pharmacotherapy with monotherapy for fibromyalgia, consequently limiting evidence to support or refute the use of combination pharmacotherapy for fibromyalgia.
Topics: 5-Hydroxytryptophan; Acetaminophen; Adult; Amitriptyline; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Benzodiazepines; Carisoprodol; Drug Therapy, Combination; Duloxetine Hydrochloride; Fibromyalgia; Fluoxetine; Humans; Magnesium; Malates; Melatonin; Monoamine Oxidase Inhibitors; Muscle Relaxants, Central; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 29457627
DOI: 10.1002/14651858.CD010585.pub2 -
Medicine Sep 2022As an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the common signs of coronavirus disease 2019 (COVID-19) are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
As an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the common signs of coronavirus disease 2019 (COVID-19) are respiratory symptoms, fever, cough, shortness of breath, and dyspnea, with multiple organ injuries in severe cases. Therefore, finding drugs to prevent and treat COVID-19 is urgently needed and expected by the public. Several studies suggested beneficial effects of melatonin for the relevant prevention and treatment. To explore the effect and safety of melatonin in the treatment and provide theoretical support and reference for seeking the most suitable drug for COVID-19, the meta-analysis was carried out accordingly.
METHODS
It included randomized clinical trials of patients with COVID-19 treated with melatonin. Total effective rate was the primary outcome, while C-reactive protein (CRP), arterial oxygen saturation (SaO2), white blood cell count (WBC) were the secondary measures. Random-effect and fixed-effect models were used to evaluate the effect size of some indicators in this meta-analysis.
RESULTS
Six eligible studies with 338 participants were included. One hundred seventy subjects were treated with melatonin adjuvant therapy and 168 subjects were assigned to the control group, with total excellent effective rate in subjects treated with melatonin [odds ratio = 3.05, 95 % confidence interval (CI) = 1.47, 6.31, P = .003]. Homogeneity was analyzed by fixed effect model (I2 = 0%). There was no significant difference in CRP between the melatonin group and the control group (weighted mean difference [WMD] = -0.36, 95% CI = -3.65, 2.92, P = .83). Significant difference was not existed in SaO2 between the melatonin treatment group and the control group (WMD = 1, 95% CI = -1.21, 3.22, P = .37). In terms of WBC, there was no significant difference between the 2 groups (WMD = -1.07, 95% CI = -2.44, 0.30, P = .13).
CONCLUSIONS
The meta-analysis showed that melatonin had the beneficial effects for COVID-19 prevention and treatment as an adjunctive agent in combination with basic treatment for the treatment.
Topics: C-Reactive Protein; Cough; Dyspnea; Humans; Melatonin; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 36181086
DOI: 10.1097/MD.0000000000030874 -
Journal of Clinical Hypertension... May 2022Oral melatonin is a potential alternative treatment for hypertension and nocturnal hypertension. However, high-quality and relevant meta-analyses are lacking. This... (Meta-Analysis)
Meta-Analysis
Oral melatonin is a potential alternative treatment for hypertension and nocturnal hypertension. However, high-quality and relevant meta-analyses are lacking. This meta-analysis aimed to investigate whether oral melatonin supplementation reduces daytime/asleep blood pressure and cardiovascular risk, improves sleep quality, and is well-tolerated compared with placebo. Relevant articles were searched in multiple databases, including MEDLINE, EMBASE, CINAHL Complete, and the Cochrane Library, from their inception to June 2021. The included studies were randomized controlled trials recruiting patients with hypertension, using oral melatonin as the sole intervention, and investigating its effect on blood pressure. The mean out-of-office (including 24-h, daytime, and asleep) systolic and diastolic blood pressures, sleep quality, and side effects were compared between the melatonin and placebo arms using pairwise random-effect meta-analyses. A risk of bias assessment was performed using the Cochrane risk-of-bias tool. Four studies were included in the analysis and only one study was considered to have a low risk of bias. No study reported on cardiovascular risk or outcomes. Only controlled-release melatonin (not an immediate-release preparation) reduced asleep systolic blood pressure by 3.57 mm Hg (95% confidence interval: -7.88 to .73; I = 0%). It also reduced asleep and awake diastolic blood pressure, but these differences were not statistically significant. Melatonin improves sleep efficacy and total sleep time and is safe and well-tolerated. Due to the limited number of high-quality trials, the quality of evidence was low to very low. Therefore, adequately powered randomized controlled trials on melatonin are warranted.
Topics: Blood Pressure; Delayed-Action Preparations; Dietary Supplements; Humans; Hypertension; Melatonin; Randomized Controlled Trials as Topic
PubMed: 35388609
DOI: 10.1111/jch.14482