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Effects of Melatonin Supplementation on Insulin Levels and Insulin Resistance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Li, Y, Xu, Z
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2021;(9):616-624
Abstract
Insulin resistance (IR) is a pivotal process in various metabolic diseases. The well-known treatment is lifestyle modification and medication therapy, which may result in poor compliance and side effects. Melatonin has been suggested to have a role in glucose metabolism, yet the results across studies have been inconsistent. Therefore, we performed a systematic review to evaluate the effects of melatonin supplementation on insulin levels and IR. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov, and identified randomized controlled trials (RCTs) published prior to August 2020. Articles were reviewed, selected and extracted by two reviewers independently. In total, 8 RCTs of 376 participants were included. Data were pooled using a random-effects model, with mean differences (MDs) and 95% confidence intervals (CIs). Our results showed that melatonin administration significantly reduced insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR), and increased the quantitative insulin sensitivity check index (QUICKI). We conclude that melatonin ameliorated hyperinsulinemia, insulin resistance, and insulin sensitivity, and the results are an update of a previous meta-analysis. Although more investigations are required, we clearly provide evidence for the use of melatonin as an adjuvant treatment for metabolic disorders involving IR.
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2.
The association between melatonin and episodic migraine: A pilot network meta-analysis of randomized controlled trials to compare the prophylactic effects with exogenous melatonin supplementation and pharmacotherapy.
Tseng, PT, Yang, CP, Su, KP, Chen, TY, Wu, YC, Tu, YK, Lin, PY, Stubbs, B, Carvalho, AF, Matsuoka, YJ, et al
Journal of pineal research. 2020;(2):e12663
Abstract
Although exogenous melatonin supplementation has been suggested to be effective for episodic migraine prophylaxis, there is no conclusive evidence comparing the efficacy of exogenous melatonin supplementation to the other FDA-approved pharmacotherapy for episodic migraine prophylaxis. The aim of the current network meta-analysis (NMA) was to compare the efficacy of exogenous melatonin supplementation in patients with episodic migraine. The randomized placebo-controlled trials or randomized controlled trials (RCTs) incorporating a placebo in the study designs were included in our analyses. All of the NMA procedures were conducted under the frequentist model. The primary outcome was changes in frequency of migraine days and response rate after migraine prophylaxis with melatonin supplementation or pharmacological interventions. We included 25 RCTs in total with 4499 patients (mean age = 36.0 years, mean female proportion = 78.9%). The NMA demonstrated that migraine prophylaxis with oral melatonin 3 mg/d (immediate-release) at bedtime was associated with the greatest improvement in migraine frequency [mean difference = -1.71 days, 95% confidence interval (CI): -3.27 to -0.14 days compared to placebo] and the second highest response rate (odds ratio = 4.19, 95% CI = 1.46 to 12.00 compared to placebo). Furthermore, oral melatonin 3 mg (immediate-release) at bedtime was the most preferred pharmacological intervention among all of the investigated interventions when improvements in migraine frequency, response rate, dropout rate, and rates of any adverse events were taken into account. This pilot NMA suggests the potential prophylactic role of exogenous melatonin supplementation in patients with episodic migraine.
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3.
Melatonergic agents in the prevention of delirium: A network meta-analysis of randomized controlled trials.
Yang, CP, Tseng, PT, Pei-Chen Chang, J, Su, H, Satyanarayanan, SK, Su, KP
Sleep medicine reviews. 2020;:101235
Abstract
Disruption of the sleep-wake cycle is a risk factor and a prodromal indicator of delirium. Melatonergic agents may thus play a role in the prevention of delirium. Based upon literature search on eight databases, this systemic review and frequentist model network meta-analysis (NMA) aimed to determine the efficacy and tolerability of melatonergic agents in delirium prevention. Six randomized controlled trials (RCTs) were included with a total of 913 adult participants (mean age = 78.8, mean female proportion = 59.4%) investigating the preventive effects of melatonergic agents in patients with high risks of developing delirium. The outcomes of NMA demonstrated significant preventive effects with 5 mg/day of melatonin [Odds Ratio (OR) = 0.21, 95% Confidence Intervals (CIs): 0.07 to 0.64], melatonin (0.5 mg/d) [OR = 0.16 (95% CIs: 0.03 to 0.75)], and ramelteon (8 mg/d) [OR = 0.28 (95% CIs: 0.12 to 0.65)] against placebo groups. According to the surface under the cumulative ranking curve (SUCRA), 0.5 mg/d of melatonin was associated with the best preventive effect. Our findings provided the rationale for recommending low-dose melatonergic agents for delirium prevention in the practice guidelines.
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4.
The effect of melatonin supplementation on liver indices in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized clinical trials.
Mansoori, A, Salimi, Z, Hosseini, SA, Hormoznejad, R, Jafarirad, S, Bahrami, M, Asadi, M
Complementary therapies in medicine. 2020;:102398
Abstract
Several randomized clinical trials (RCTs) evaluated the effect of melatonin supplementation on liver enzymes in patients with non-alcoholic fatty liver disease (NAFLD) and reported conflicting results. To meet these discrepancies, a meta-analysis was conducted to evaluate the eff ;ect of melatonin on liver indices in patients with NAFLD. To collect the required data, a thorough search was conducted through Web of science, Pubmed, Cochrane database, Embase, Google Scholar, ProQuest, and Scopus databases. The aim was to find clinical trials over the effect of melatonin supplementation on liver indices up to 16 May 2019. As a result, five eligible articles were selected and analysed in this meta-analysis using a fixed-effects model. Heterogeneity test was performed by I2 statistics and Cochrane Q test. The results showed that melatonin had a significant effect on aspartate aminoteransferase (AST) (WMD = 2.29, [95 %CI: 1.14, 3.43] IU/L, p = <0.001), alkaline phosphatase (ALP) (WMD = -8.40, [95 %CI -11.33, -5.48] IU/L, p < 0.001), and gamma-glutamyltransferase (GGT) (WMD = -33.37, [95 %CI: -37.24, -29.49] IU/L, p= < 0.001). Melatonin had no significant effect on alanine aminotransferase (ALT) regarding the overall effect size. Based on this meta-analysis, melatonin supplementation can improve liver indices. However, more RCTs are required with larger sample sizes and better control of confounding variables such as weight, body mass index, and gender to determine the effect of melatonin on patients with non-alcoholic fatty acid disease.
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The effect of melatonin supplementation on lipid profile and anthropometric indices: A systematic review and meta-analysis of clinical trials.
Loloei, S, Sepidarkish, M, Heydarian, A, Tahvilian, N, Khazdouz, M, Heshmati, J, Pouraram, H
Diabetes & metabolic syndrome. 2019;(3):1901-1910
Abstract
BACKGROUND Epidemiological evidence suggests that melatonin has some effects on the serum lipid. However, these results are controversial. The aim of this systematic review and meta-analysis is to examine the effect of melatonin supplement on dyslipidemia and anthropometric indices. METHODS We searched electronic databases including Medline, Embase, Scopus, Web of Science and Cochrane Library up to Des 2018 without any language restriction. To compare the effects of melatonin with placebo, differences in standardized means difference (SMD) with 95% confidence intervals (95% CI) were pooled using random effects model. RESULTS Twelve trials including 641 participants included in meta-analysis finally. The dose of melatonin was reported at 0.8-30 mg. Comparing with the control group, melatonin may improve low density lipoprotein cholesterol (LDL-C) (-0.31 mmol/L, 95% CI (-0.61, 0.01), P = 0.049, I2 = 42%) and triglyceride (TG) level (SMD = -0.45 mmol/L; 95% CI, -0.77, -0.13, P = 0.006, I2 = 47%). No significant effect of melatonin on high density lipoprotein cholesterol (HDL-C) and anthropometric indices was found. CONCLUSIONS The results of our systematic review and Meta-analyzes showed that supplementation of melatonin could be effective in improving lipid parameters and should be considered in the prevention of cardiovascular disease, although the effect of this supplement on anthropometric indices needs further investigation.
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6.
The Effects of Melatonin Supplementation on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Doosti-Irani, A, Ostadmohammadi, V, Mirhosseini, N, Mansournia, MA, Reiter, RJ, Kashanian, M, Rahimi, M, Razavi, M, Asemi, Z
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2018;(11):783-790
Abstract
This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to clarify the effect of melatonin supplementation on glycemic control. Databases including PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched until July 30th, 2018. Two reviewers independently assessed study eligibility, extracted data, and evaluated the risk of bias for included trials. Heterogeneity among included studies was assessed using Cochran's Q test and I-square (I2) statistic. Data were pooled using random-effect models and standardized mean difference (MD) was considered as the overall effect size. Twelve trials out of 292 selected reports were identified eligible to be included in current meta-analysis. The pooled findings indicated that melatonin supplementation significantly reduced fasting glucose (SMD=-6.34; 95% CI, -12.28, -0.40; p=0.04; I2: 65.0) and increased the quantitative insulin sensitivity check index (QUICKI) (SMD=0.01; 95% CI, 0.00, 0.02; p=0.01; I2: 0.0). However, melatonin administration did not significantly influence insulin levels (SMD=-1.03; 95% CI, -3.82, 1.77; p=0.47; I2: 0.53), homeostasis model assessment of insulin resistance (HOMA-IR) (SMD=-0.34; 95% CI, -1.25, 0.58; p=0.37; I2: 0.37) or HbA1c levels (SMD=-0.22; 95% CI, -0.47, 0.03; p=0.08; I2: 0.0). In summary, the current meta-analysis showed a promising effect of melatonin supplementation on glycemic control through reducing fasting glucose and increasing QUICKI, yet additional prospective studies are recommended, using higher supplementation doses and longer intervention period, to confirm the impact of melatonin on insulin levels, HOMA-IR and HbA1c.
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7.
The effects of melatonin supplementation on inflammatory markers among patients with metabolic syndrome or related disorders: a systematic review and meta-analysis of randomized controlled trials.
Akbari, M, Ostadmohammadi, V, Tabrizi, R, Lankarani, KB, Heydari, ST, Amirani, E, Reiter, RJ, Asemi, Z
Inflammopharmacology. 2018;(4):899-907
Abstract
OBJECTIVE This systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out to determine the effect of melatonin supplementation on the inflammatory markers among individuals with metabolic syndrome (MetS) and related disorders. METHODS We searched the following databases up to March 2018: PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Three reviewers independently assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies. Statistical heterogeneity was assessed using Cochran's Q test and I-square (I2) statistic. Data were pooled using the random effect model and standardized mean difference (SMD) was considered as the summary effect size. RESULTS Six trials of 317 potential reports were identified to be suitable for our meta-analysis. The pooled results using random effects model indicated that melatonin supplementation significantly reduced C-reactive protein (CRP) (SMD = - 1.80; 95% CI - 3.27, - 0.32; P = 0.01; I2: 95.2) and interleukin 6 (IL-6) concentrations (SMD = - 2.02; 95% CI - 3.57, - 0.47; P = 0.01; I2: 91.2) among patients with MetS and related disorders; however, it did not affect tumor necrosis factor-α (TNF-α) concentrations (SMD = - 1.87; 95% CI - 3.81, 0.07; P = 0.05; I2: 94.4). CONCLUSIONS In summary, the current meta-analysis showed the promising effect of melatonin administration on reducing CRP and IL-6, but not TNF-α levels among patients with MetS and related disorders. Additional prospective studies are recommended using higher supplementation doses and longer intervention period.