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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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... According to Reiter et al. 3 and Loloei et al. 53 , melatonin plays an important role in phase shifting/synchronizing the circadian rhythm of energy metabolism, in which the anti-obesogenic effect of melatonin can lead to a reduction in body weight 17,54 . Therefore, the melatonin antiobesogenic effect would be linked to its phase shifting effect. ...
... In a review, Loloei et al. 53 analyzed the effect of melatonin supplementation on anthropometric parameters and found no statistically significant reduction in BMI, body weight and waist circumference after melatonin supplementation. Of a total of six reviewed articles, only one, performed with postmenopausal women, reported a decrease in BMI with melatonin (5 mg, 24 weeks). ...
Article
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Shift workers experience chronic circadian misalignment, which can manifest itself in reduced melatonin production, and has been associated with metabolic disorders. In addition, chronotype modulates the effect of night shift work, with early types presenting greater circadian misalignment when working night shift as compared to late types. Melatonin supplementation has shown positive results reducing weight gain in animal models, but the effect of exogenous melatonin in humans on body weight in the context of shift work remains inconsistent. The aim of this study was thus to evaluate the effects of exogenous melatonin on circadian misalignment and body weight among overweight night shift workers, according to chronotype, under real life conditions. We conducted a double-blind, randomized, placebo-controlled, crossover trial where melatonin (3 mg) or placebo was administered on non-night shift nights for 12 weeks in 27 female nurses (37.1 yo, ±5.9 yo; BMI 29.9 kg/m 2 , ±3.3 kg/m 2). Melatonin (or placebo) was only taken on nights when the participants did not work night shifts, that is, on nights when they slept (between night shifts and on days-off). Composite Phase Deviations (CPD) of actigraphy-based midsleep timing were calculated to measure circadian misalignment. The analyses were performed for the whole group and by chronotype. We found approximately 20% reduction of circadian misalignment after exogenous melatonin administration considering all chronotypes. Moreover, melatonin supplementation in those who presented high circadian misalignment, as observed in early chronotypes, reduced body weight, BMI, waist circumference, and hip circumference, without any change in the participants' calorie intake or physical activity levels.
... Melatonin (N-acetyl-5-methoxytryptamine) is an endogenous indoleamine that is mainly secreted by the pineal gland and has a remarkable range of physiological functions and effects, such as circadian rhythm regulation [11], anti-atherosclerosis [12], anti-inflammation [13], anti-oxidation [14], and immune regulation [15]. Two separate meta-analysis studies have shown that melatonin supplementation could reduce the level of triglycerides (TGs), but its effects on LDL-C are inconsistent [16,17]. Koziróg et al. demonstrated that patients with metabolic syndrome who received melatonin (5 mg/day) for 2 months showed a significant reduction in LDL-C [18]. ...
... A growing body of clinical data has revealed that melatonin could improve dyslipidemia and reduce the risk of cardiovascular events in patients with hyperlipidemia [16,17]. Melatonin can also improve lipid dysmetabolism in high-fat-diet-fed mice by reprogramming gut microbiota [36]. ...
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Background: Cigarette smoke (CS) exposure impairs serum lipid profiles and the function of vascular endothelial cells, which accelerates the atherosclerosis. However, the precise mechanism and effect on the expression of low-density lipoprotein receptor (LDLR) in the liver by CS exposure is still unclear. Methods: In this study, adult male C57BL/6 J mice were divided into three groups, with one group being exposed to CS for 6 weeks. HepG2 cells were treated with CS extract at concentrations of 1, 2.5, 5, and 10%. Results: The serum levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) for the CS-exposure group were significantly higher than those in the control group (P < 0.05). Moreover, CS exposure decreased the LDLR expression in the hepatocytes and promoted inflammation in the blood vessel walls. Melatonin was intraperitoneally injected at 10 mg/kg/d for 6 weeks alongside CS exposure, and this significantly decreased the levels of TC, TGs, and LDL-C and decreased the expression of intercellular adhesion molecule-1 and the infiltration of cluster determinant 68-cells. In vitro, CS extract prepared by bubbling CS through phosphate-buffered saline decreased the LDLR expression in HepG2 cells in a time- and concentration-dependent manner, and this effect was prevented by pretreatment with 100 μM melatonin. Conclusions: In conclusion, CS exposure impaired lipid metabolism and decreased LDLR expression in hepatocytes, and these effects could be prevented by melatonin supplementation. These findings implied that melatonin has the potential therapeutic applicability in the prevention of lipid metabolic disorder in smokers.
... A meta-analysis of 12 randomized controlled trials found that melatonin ameliorates dyslipidemia and reduces LDL-C and triglyceride levels (43). In addition, studies have shown that treatment with melatonin regulates dyslipidemia in rats (44)(45)(46) and can reprogram the gut microbiota to improve lipid dysmetabolism in mice fed a high-fat diet (47). ...
Article
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Cigarette smoke (CS) exposure is a risk factor for dyslipidemia and atherosclerosis. Reduced expression of low‑density lipoprotein receptor (LDLR) in hepatocytes may be one of the underlying mechanisms for these disorders. The aim of the present study was to investigate the molecular mechanism underlying the regulatory effect of CS extract (CSE) on proprotein convertase subtilisin/kexin type 9 (PCSK9) and low LDLR expression in HepG2 cells. PCSK9 and LDLR mRNA and protein expression levels in HepG2 cells were evaluated after CSE treatment via reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. In addition, total intracellular reactive oxygen species (ROS) production was determined via 2,7‑dichlorofluorescein diacetate fluorescence. CSE significantly increased PCSK9 expression and inhibited LDLR expression in a time‑ and concentration‑dependent manner. Furthermore, CSE significantly induced ROS production and nuclear factor κB (NF‑κB) activation. However, pretreatment with a ROS scavenger or an NF‑κB inhibitor significantly attenuated the CSE‑induced changes in PCSK9 and LDLR expression. In addition, pretreatment with melatonin markedly reduced ROS production, NF‑κB activation and PCSK9 expression, and increased LDLR expression in the CSE‑treated cells. These data suggest that melatonin inhibits CSE‑regulated PCSK9 and LDLR production in HepG2 cells via ROS/NF‑κB signaling.
... В нашем исследовании преобладали пациенты в возрасте от 40 до 59 лет (73 человека, 72,3%), средний возраст пациентов в группах составил 44,2±9,2; 49,9±9,3; 50,2±6,8 и 41,9±9,1 года, что позволяет исклю-чить выраженные колебания уровня мелатонина, связанные с возрастом. Также данные систематических обзоров показывают влияние мелатонина на массу тела, но не зависимость его уровня от массы тела [16]. ВЫВОДЫ 1. У пациентов с гастроэзофагеальной рефлюксной болезнью, ассоциированной с синдромом обструктивного апноэ/гипопноэ сна, повышен уровень 6-сульфатоксимелатонина в суточной моче, а также в дневной и ночной её порциях по отношению к пациентам с гастроэзофагеальной рефлюксной болезнью без сопутствующего синдрома обструктивного апноэ/гипопноэ сна (р=0,0000, р=0,0000 и р=0,015 соответственно), а также в дневной порции мочи по отношению к группе сравнения (р=0,029). ...
Article
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Aim. To evaluate the features of melatonin cyrcadian production in patients with gastroesophageal reflux disease associated with obstructive sleep apnea/hypopnea syndrome. Methods. We examines 29 patients with gastroesophageal reflux disease were examined (group 1), 29 patients with gastroesophageal reflux disease associated with obstructive sleep apnea/hypopnea syndrome (group 2), and 22 patients with obstructive sleep apnea/hypopnea syndrome (group 3). The comparison group included 21 people without gastroesophageal reflux disease and obstructive sleep apnea/hypopnea syndrome (group 4). The content of 6-sulfatoxymelatonin was determined in 24-hour urine and separately in its daytime and night portions by enzyme immune assay. The night/day index was calculated. The compared groups were comparable by gender but the patients with obstructive sleep apnea/hypopnea syndrome and gastroesophageal reflux disease associated with this syndrome differed from the patients from comparison group by older age, which is consistent with epidemiology of sleep apnea. The analysis of the data obtained was performed using the program Statistica 10.0. When comparing quantitative indicators between four independent samples, KruskelWallis test was used. In order to study the relationship between the phenomena, the Spearman rank correlation coefficient was calculated. Results. A significantly increased level of 6-sulfatoxymelatonin in 24-hour urine was determined in group 2 (p=0.0000), as well as in day (0.0000) and night portions (0.015) compared to group 1, in 24-hour urine (p=0.0007) and its day portion (p=0.0001) compared to group 3, in day portion of urine compared to group 4 (p=0.029). In group 2 compared to group 4 a significant shift in melatonin synthesis peak during daytime hours was observed, which is expressed in a statistically significant decrease in the night/day index (p=0.0003). Correlation analysis revealed statistically significant relations between the level of 6-sulfatoxymelatonin in urine and the severity of sleep apnea (in 24-hour urine: r=0.64, p=0.0000; in daytime portion: r=0.62, p=0.0000; in night portion: r=0.40, p=0.003), as well as respiratory monitoring indicators indicating sleep fragmentation due to apnea (the number of awakenings associated with respiratory events: r=0.58; p=0.00001; activation of the central nervous system associated with respiratory efforts: (r=0.50; p=0.0002). Conclusion. The patients with gastroesophageal reflux disease associated with obstructive sleep apnea/hypopnea syndrome have an increased level of 6-sulfatoxymelatonin in urine associated with the shift of its peak synthesis to daytime hours; the identified changes correlate with apnea/hypopnea index reflecting the severity of apnea and sleep disturbance.
... Кореляційний аналіз показав, що збільшення ІМТ та об'єму талії у хворих, яким проводять ГД, поєднується зі зниженням концентрації мелатоніну в ден- [11,14]. Встановлено зворотний кореляційний зв'язок між показником центральної гемодинаміки -рівнем САТ та концентрацією мелатоніну в денний та сильніший -у нічний час (рис. ...
... Therefore, melatonin is antioxidant, anti-inflammatory, as well as regulator of insulin secretion and lipid metabolism that reduces liver fat accumulation [6]. Two systematic reviews and meta-analysis showed improving effect of melatonin supplementation on lipid profile [7,8]. In the liver, melatonin scavenges free radicals to prevent lipid peroxidation and lipid membrane peroxidation, which has a main role in progression of steatosis to steatohepatitis, necrosis of liver cells, inflammation, stress oxidative, rising transaminases, and fibrosis. ...
Article
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 effect 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.
... mmol / L; 95% CI, -0.77, -0.13, P = 0.006, I2 = 47%). There was no significant effect of MEL on HDL-C and anthropometric indices [152][153][154][155]. ...
Article
Significance Obesity is a multifactorial disease with many risks to public health, affecting 39.6% of American adults and 18.5% of young people. Brazil ranks fifth in the world ranking, with about 18 million obese people. It is estimated that 415 million people live with diabetes in the world, which is roughly 1 in 11 of the world's adult population. This is expected to rise to 642 million people living with diabetes worldwide by 2040. In this scenario, Melatonin has evidenced an important function in the regulation of energy metabolism. Objective to carry out a broad narrative review of the literature on the main aspects of the influence of melatonin on Diabetes Mellitus and obesity. Methods Article reviews, systematic reviews, prospective studies, retrospective studies, randomized, double-blind, placebo-controlled trials in humans recently published were selected and analyzed. A total of 368 articles were collated and submitted to the eligibility analysis. Subsequently, 215 studies were selected to compose the textual part of the manuscript and 153 to compose the Narrative Review. Results and final considerations Studies suggest a possible role of melatonin in metabolic diseases such as obesity, T2DM and metabolic syndrome. Intervention studies using this hormone in metabolic diseases are still unclear regarding a possible benefit of it. There is so far no consensus about a possible role of melatonin as an adjuvant in the treatment of metabolic diseases. More studies are necessary to define possible risks and benefits of melatonin as a therapeutic agent.
... In the meta-analysis of Mostafavi and colleagues published in 2017 [89], which covered seven clinical trials and a total of 244 participants based on Mostafavi's inclusion criteria, melatonin supplementation alone was ineffective in inducing weight loss, but showed a positive effect when combined with other strategies. A more recent meta-analysis, published in 2019, showed that melatonin supplementation alone improved selected lipid biomarkers but was ineffective in inducing weight loss [90]. Such result was found based on their inclusion criteria, which selected 12 trials, from whom a subset of 6 trials was examined for effects on weight loss, covering a population of 338 individuals. ...
Article
Despite the evolving advances in clinical approaches to obesity and its inherent comorbidities, the therapeutic challenge persists. Among several pharmacological tools already investigated, recent studies suggest that melatonin supplementation could be an efficient therapeutic approach in the context of obesity. In the present review, we have amalgamated the evidence so far available on physiological effects of melatonin supplementation in obesity therapies, addressing its effects upon neuroendocrine systems, cardiometabolic biomarkers and body composition. Most studies herein appraised employed melatonin supplementation at dosages ranging from 1 to 20 mg/day, and most studies followed up participants for periods from 3 weeks to 12 months. Overall, it was observed that melatonin plays an important role in glycaemic homeostasis, in addition to modulation of white adipose tissue activity and lipid metabolism, and mitochondrial activity. Additionally, melatonin increases brown adipose tissue volume and activity, and its antioxidant and anti-inflammatory properties have also been demonstrated. There appears to be a role for melatonin in adiposity reduction; however, several questions remain unanswered, for example melatonin baseline levels in obesity, and whether any seeming hypomelatonaemia or melatonin irresponsiveness could be clarifying factors. Supplementation dosage studies and more thorough clinical trials are needed to ascertain not only the relevance of such findings but also the efficacy of melatonin supplementation.
... Due to its prominent role in the etiology of many chronic diseases, OS has become a widely studied phenomenon and researchers are constantly looking for an ideal, safe and effective antioxidant to combat it. Melatonin is one of these compounds that has been widely considered as an effective antioxidant for the treatment of OS [8]. ...
Article
Background Oxidative stress, defined as an imbalance between pro-oxidants and neutralizing antioxidants within the body, is a growing public health concern. Oxidative stress is involved in the progression of nearly all chronic diseases. Melatonin has been suggested to reduce oxidative stress by its potential radical scavenging properties. Objective To determine the efficacy and safety of melatonin as a therapy for the improvement of oxidative stress parameters in randomized controlled trials. Methods A systematic database search using Scopus, PubMed/Medline, EMBASE, Web of Science, the Cochrane Controlled Register of Trials and clinicaltrials.gov (https://clinicaltrials.gov) for studies published up to July 2020 was conducted. We included studies which investigated the effect of supplemental melatonin compared to placebo on oxidative stress parameters in unhealthy patients. Quantitative data synthesis was conducted using a random-effects model with standard mean difference (SMD) and 95 % confidence intervals (CI). Cochrane’s Q and I² values were used to evaluate heterogeneity. Results A total of 12 randomized controlled trials (RCTs) were eligible. The meta-analysis indicated an association between melatonin intake and a significant increase in total antioxidant capacity (TAC) (SMD: 0.76; 95 % CI: 0.30, 1.21; I² = 80.1 %), glutathione (GSH) levels (SMD: 0.57; 95 % CI: 0.32, 0.83; I² = 15.1 %), superoxide dismutase (SOD) (SMD: 1.38; 95 % CI: 0.13, 2.62; I² = 86.9 %), glutathione peroxidase (GPx) (SMD: 1.36; 95 % CI: 0.46, 2.30; I² = 89.3 %), glutathione reductase (GR) (SMD: 1.21; 95 % CI: 0.65, 1.77; I² = 00.0 %) activities, and a significant reduction in malondialdehyde (MDA) levels (SMD: -0.79; 95 % CI: -1.19, -0.39; I² = 73.1 %). Melatonin intake was not shown to significantly affect nitric oxide (NO) levels (SMD: -0.24; 95 % CI: -0.61, 0.14; I² = 00.0 %) or catalase (CAT) activity (SMD: -1.38; 95 % CI: -1.42, 4.18; I² = 96.6 %). Conclusion Melatonin intake was shown to have a significant impact on improving Oxidative stress parameters. However, future research through large, well-designed randomized controlled trials are required to determine the effect of melatonin on oxidative stress parameters in different age groups and different disease types.
... It is worth mentioning that the bioavailability of NAC is reported to be reduced in case of NAC oral administration [19]. However, there are some other meta-analysis in line with our results that did not demonstrate any impact of antioxidants on weight changes [49][50][51]. Overall, it seems that the results are controversial among different studies [32]. ...
Article
Background: N-acetyl cystatin (NAC) potentially can contribute to weight changes due to its antioxidant activities. Aim of the review: we carried out a systematic review and meta-analysis of randomized clinical trials in order to examine whether NAC consumption can result in any changes in anthropometric indices. Methods: Using appropriate keywords, we searched online databases of PubMed-Medline, SCOPUS, Web of Science, Embase databases and Google Scholar published for relevant articles up to Nov 2019. Random-effect model was employed to report weighted mean differences. Sensitivity and subgroup analyses were carried out. Results: A number of 7 eligible studies were identified. The results indicated no significant effect of NAC on BMI, weight and WC (SMD=-0.08 Kg/m2 ; CI: -0.25, 0.08; P = 0.335, I2 = 0.0 %, P = 0.967), (SMD= -0.38 Kg; 95 % CI: -2.11, 2.87; P = 0.766, I2 = 0.0 %, P = 0.691) and (SMD= -0.22 Cm; 95 % CI: 0.52, 0.08; p = 0.153, I2 = 0.0 %, P = 0.826), respectively. No effect of sensitivity and subgroup analyses were observed. Conclusion: There was no significant effect of NAC supplementation on obesity indices. As far as we assessed anthropometric factors mainly as the secondary outcome in these studies rather than the main outcome, more specific trials are suggested to assess this relationship precisely.
... There is no data available regarding the effect of melatonin on the nicotineinduced changes in lipid profile, but Agil et al. (2011) andNduhirabandi et al. (2014) reported that melatonin administration decreased plasma triglyceride and cholesterol and increased plasma HDL levels in obese rats. Moreover, Loloei et al. (2019) found that administration of melatonin could be effective in the improvement of the lipid profile through decreasing triglycerides and LDL levels of smokers. ...
Article
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The present study was carried out to investigate the ameliorative effects of melatonin against nicotine-induced heart and lung toxicity. For this purpose, 75 mature male Sprague Dawley (SD) rats weighing 150–170 g were randomly divided into five groups (15 rats each): control group (rats were I/P injected with 1% ethanol in saline), nicotine group (rats were I/P injected with 0.6 mg/kg body weight), and combined nicotine and melatonin groups (rats received nicotine as in the previous group and melatonin at a dose of 1, 5, or 10 mg/kg body weight, respectively); all treatments were continued for 21 days. Fasting blood samples were collected from each rat at the 11th day and one day after the end of the last injection (22nd day) for complete blood count (CBC) determination, while sera were collected for the determination of lipid profiles. Malondialdehyde (MDA) concentration, superoxide dismutase (SOD) activity, and reduced glutathione (GSH) as well as DNA fragmentation percentage were assessed in cardiac tissue. Heart and lung samples were collected for estimation of caspase-3 expression and histopathological examination. The results revealed that nicotine increased the number of RBCs, Hb concentration, total cholesterol, and low density lipoprotein (LDL) and decreased high density lipoprotein (HDL). In addition, it decreased SOD activity and GSH concentration with increased MDA concentration, and DNA fragmentation in the heart, as well as caspase-3 expression in both heart and lungs. It also induced histopathological changes in the heart and lung tissues. Melatonin could ameliorate the deleterious effect of nicotine on the previous parameters either partially or completely, where melatonin restored complete blood count, improved lipid profile, mended lipid peroxidation and antioxidant parameters in the cardiac tissue, rectified caspase-3 expression in the heart and lungs, ameliorated DNA fragmentation percentage in the heart, and protected both heart and lung tissue against the harmful effect of nicotine. It is concluded that melatonin has a protective effect on the heart and lungs against the harmful effect of nicotine.
... It is known that dyslipidemia triggered by obesity plays an important role in the development and worsening of the inflammatory state [41]. Here, we have shown that melatonin supplementation was effective in partially preventing the increase in total cholesterol, LDL-cholesterol and triglycerides characteristic of DIO. ...
Article
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Obesity is defined as a condition of abnormal or excessive fat accumulation in white adipose tissue that results from the exacerbated consumption of calories associated with low energy expenditure. Fat accumulation in both adipose tissue and other organs contributes to a systemic inflammation leading to the development of metabolic disorders such as type 2 diabetes, hypertension, and dyslipidemia. Melatonin is a potent antioxidant and improves inflammatory processes and energy metabolism. Using male mice fed a high-fat diet (HFD—59% fat from lard and soybean oil; 9:1) as an obesity model, we investigated the effects of melatonin supplementation on the prevention of obesity-associated complications through an analysis of plasma biochemical profile, body and fat depots mass, adipocytes size and inflammatory cytokines expression in epididymal (EPI) adipose depot. Melatonin prevented a gain of body weight and fat depot mass as well as adipocyte hypertrophy. Melatonin also reversed the increase of total cholesterol, triglycerides and LDL-cholesterol. In addition, this neurohormone was effective in completely decreasing the inflammatory cytokines leptin and resistin in plasma. In the EPI depot, melatonin reversed the increase of leptin, Il-6, Mcp-1 and Tnf-α triggered by obesity. These data allow us to infer that melatonin presents an anti-obesity effect since it acts to prevent the progression of pro-inflammatory markers in the epididymal adipose tissue together with a reduction in adiposity.
... 24 Moreover, it remains unclear whether the long-term use of melatonin reduces cardiovascular events. However, long-term use of CR melatonin may reduce cardiovascular risk and events because it also reduces hyperglycemia and hyperlipidemia, which are important comorbidities and cardiovascular risk factors in patients with HT. 25,26 For researchers, an adequately powered RCT is urgently needed to confirm the effect of melatonin on both daytime and asleep BP. Second, the characteristics of responders to melatonin remain unknown. ...
Article
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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; I2 = 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.
... A 2017 meta-analysis that included six unique studies and 244 patients found null results for body weight [15]. Another meta-analysis with six studies and 338 individuals was unable to demonstrate significant effects of melatonin supplementation on body weight compared with placebo [43]. We included 16 studies and >1065 individuals between the intervention and control groups, which can explain the difference between the results. ...
Article
Objective According to in vivo and in vitro studies, melatonin appears as a potential supplement for obesity reduction. This study aimed to review the literature on randomized clinical trials that evaluated the effects of melatonin supplementation on anthropometric indicators of obesity in humans. Research Methods & Procedures We conducted a systematic review with meta-analysis in the following databases: Pubmed, LILACS, Scielo, Scopus, Web of Science, Cochrane, and Embase. We included studies that evaluated melatonin supplementation's effects, compared to placebo, on anthropometric measures, including body weight, BMI, and waist circumference, in people aged 18 and over. This systematic review and meta-analysis were registered on PROSPERO: CRD42021241079. Results Twenty-three studies were included, of which eleven showed significant results from melatonin supplementation on weight loss, BMI, or waist circumference, compared to placebo. In the meta-analysis, melatonin supplementation significantly reduced body weight [SMD: -0.48; 95% CI: -0.94, -0.02; p = <0.01; I² = 92%]. Results for BMI and waist circumference were null. The I² tests were significant for the analyses with significant results. Conclusion Our results demonstrated that melatonin supplementation was responsible for significantly reducing body weight. More studies are needed until melatonin can be recommended for weight loss.
... However, the current data are mainly focused on short-term effects on BP, 146,147 whereas the evidence on the long-term prognostic impact of such approaches is rather scarce. 148 Dietary melatonin supplementation is associated with favorable cardiometabolic changes, including improved lipid profile 149,150 and glucose metabolism. 151 Experimental studies show that melatonin can ameliorate insulin resistance and reverse cardiovascular remodeling. ...
Article
Sleep is essential for healthy being and healthy functioning of human body as a whole, as well as each organ and system. Sleep disorders, such as sleep-disordered breathing, insomnia, sleep fragmentation, and sleep deprivation are associated with the deterioration in human body functioning and increased cardiovascular risks. However, owing to the complex regulation and heterogeneous state sleep per se can be associated with cardiovascular dysfunction in susceptible subjects. The understanding of sleep as a multidimensional concept is important for better prevention and treatment of cardiovascular diseases.
... Melatonin can regulate the activation of the immune system, thus ameliorating oxidative stress by scavenging reactive chemical species or upregulating the activities of antioxidant defense systems (Calvo et al., 2013;García et al., 2014). Melatonin supplementation can also improve the management of obesity and obesity-associated disorders (Loloei et al., 2019), prevent cardiovascular diseases (Genario et al., 2021), and have multiple therapeutic effects against tumors (Kong et al., 2020), amongst others. ...
Article
Melatonin is produced by plants, algae, and animals. Worldwide studies show diverse positive effects of exogenous melatonin on plants, edible plant products, and algae, but the potential of melatonin to enhance food and feed systems through these positive effects remains largely unexplored. Through a meta-analysis of about 25,000 observations, we show for the first time that exogenous application of melatonin significantly increases crop productivity and yields, and enhances the nutritional and nutraceutical value of edible plant products and algae by regulating diverse biological functions. We demonstrate that melatonin can improve plants, edible plant products, and algae under various current climate change scenarios, environmental pollution factors, and other stresses by about 7% to nearly 30%, on average, depending on the stressor. We also analyze various technical/methodological factors influencing the desired outcomes and identify conditions that offer optimal enhancement. We show that the positive effect of melatonin on plants and edible plant products varies among species, genera, and families, and strongly depends on the concentration of melatonin and treatment duration. The effect of melatonin is slightly lower on the monocot clade Commelinids than on the eudicot clades Asterids and Rosids. We also show that its stimulatory effect on plants depends on cultivation system, with a larger effect obtained in hydroponic systems. However, it does not depend on application stage (seed or vegetative), application route (foliage, roots, or seed), and whether the cultivation system is ex vivo or in vivo. This is the first meta-analysis examining the effects of melatonin on plants, edible plant products, and algae, and offers a scientific and technical roadmap facilitating sustainable food and feed production through the application of exogenous melatonin.
... Nevertheless, a recent meta-analysis on clinical trial studies showed that daily melatonin intake did not impact anthropometric parameters including body weight, BMI, and WC [40]. One of the studies included in this metaanalysis is a study conducted in 2015 in Poland. ...
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Obesity, as the most common metabolic disorder in the world, is characterized by excess body fat. This study is aimed at determining the effects of melatonin supplementation on body weight, nody mass index (BMI), waist circumference (WC), and body fat mass percentage (BFMP) in people with overweight or obesity. Thirty eight overweight or class-I obese adult individuals were recruited in the study (8 men and 30 women). Participants prescribed a weight-loss diet and then randomly were allocated to melatonin or placebo groups. Participants received either a 3-milligram melatonin or placebo tablet per day for 12 weeks. In order to assess differences at the significance level of 0.05, repeated measure ANOVA and paired t-test were used. According to the results, a significant reduction was found in participants’ body weight, WC, and BMI in both groups (p=0.001). However, for the last six weeks, significant reductions of these parameters were observed only in the melatonin group (p=0.01). The BFMP of participants in the melatonin group showed a significant reduction at the end of the study compared to the initial measurements (p=0.008). Nevertheless, the results of the present study alone are not sufficient to conclude on the effects of melatonin consumption on anthropometric indices, and it seems that further studies are required in this regard.
... In addition, melatonin may have favorable effects on BP as a meta-analysis of 5 RCTs showed that melatonin resulted in a lower systolic and diastolic BP (by 3.43 and 3.33 mmHg) (Hadi et al., 2019). Meta-analyses found that melatonin did not result in weight reduction (Mostafavi et al., 2017), but a reduction in LDL cholesterol (-0.31 mmol/L) and triglycerides (-0.45 mmol/L) were seen (Loloei et al., 2019). Inflammatory markers were significantly reduced after melatonin supplementation (Zarezadeh et al., 2020). ...
Chapter
The circadian system involves a 24 hr pacemaker that organizes daily rhythms and synchronizes physiological functions. Circadian misalignment can occur between internal clocks and external influences (e.g., light-dark cycle, food intake) or internally between the central and peripheral clocks. Misalignment is common in shift workers and those with abnormal meal and/or sleep timing. Experimental and observational studies have linked circadian misalignment to adverse cardiometabolic health including elevated glucose levels, elevated blood pressure, dyslipidemia and cardiovascular disease. This article discusses recent findings, including emerging interventions to reduce cardiometabolic consequences of circadian misalignment such as light therapy, melatonin, sleep and meal timing interventions.
... The similar results in male C57BL/6 mice [36], Wistar rats [37], and Syrian hamsters [38] fed a high-fat diet (HFD) had shown that melatonin significantly reduced the levels of serum triglyceride (TG), TC, and low-density lipoprotein-cholesterol (LDL-C). Besides, epidemiological evidence and Meta-analyses also support the improved effects of melatonin on serum lipid profile, and suggest the preventive role in cardiovascular disease [39][40][41], but not in menopausal women [42]. The hypocholesterolemic effect of melatonin works through the augmentation of endogenous cholesterol clearance mechanisms, via the synthesis of bilirubin acid and inhibition of low-density lipoprotein receptor activity [43,44]. ...
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Obesity and its complications have become a prominent global public health problem that severely threatens human health. Melatonin, originally known as an effective antioxidant, is an endogenous hormone found throughout the body that serves various physiological functions. In recent decades, increasing attention has been paid to its unique function in regulating energy metabolism, especially in glucose and lipid metabolism. Accumulating evidence has established the relationship between melatonin and obesity; nevertheless, not all preclinical and clinical evidence indicates the anti-obesity effect of melatonin, which makes it remain to conclude the clinical effect of melatonin in the fight against obesity. In this review, we have summarized the current knowledge of melatonin in regulating obesity-related symptoms, with emphasis on its underlying mechanisms. The role of melatonin in regulating the lipid profile, adipose tissue, oxidative stress, and inflammation, as well as the interactions of melatonin with the circadian rhythm, gut microbiota, sleep disorder, as well as the α7nAChR, the opioidergic system, and exosomes, make melatonin a promising agent to open new avenues in the intervention of obesity.
... Melatonin is supposed to improve serum lipid profile in various target populations, possibly by directly regulating lipid metabolism and reducing the detrimental effect of oxidizing lipoproteins on the cardiovascular system. 28 Our insignificant results despite substantial improvement of total cholesterol, triglyceride, and LDL might be due to low sample size or lower levels of baseline lipids in our patients, as ...
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Introduction Previous studies have shown that low serum lipids and statins may be related to cerebral hemorrhage. We made the meta-analysis to evaluate the associations between serum lipid levels or statins treatment and cerebral microbleeds (CMBs) to identify whether the similar correlation also existed. Method We comprehensively searched the Medline, Embase, Cochrane library, Web of Science, only included English journal articles, and systematically collected the observational studies and randomized controlled trials (RCTs) from September 1975 to August 2021. Random-effects model was used to pool data. Statistical heterogeneity was assessed by I² statistic and chi-square. 11 items checklists recommended by the Agency for Healthcare Research and Quality (AHRQ), Newcastle–Ottawa Scale (NOS), and Cochrane Risk of Bias tool (ROB) were used to evaluate the methodological quality of cross-sectional studies, cohort studies and randomized controlled trial, respectively. Results Five cohort studies, two RCTs, and ten cross-sectional studies, including 16,637 subjects and 2663 CMBs patients, were included in our quantitative synthesis. Our study found that after adjusting the covariates, total cholesterol (TC) was significantly inversely correlated with the prevalent CMBs in any location, while total triglycerides (TG) and High-density lipoprotein (HDL) were significantly inversely associated with prevalent deep CMBs. Low-density lipoprotein (LDL) was negatively associated with incident CMBs after adjusted confounders. We did not found statistical differences between statin and CMBs after adjusted covariates. Conclusion Serum major lipid (TC TG HDL LDL) levels may be inversely associated with CMBs. Currently, no sufficient evidence proves that statin therapy is the risk factor of CMBs.
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Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
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The metabolic syndrome (MetS) is a cluster of metabolic abnormalities associated with increased risk for cardiovascular diseases. Apart from its powerful antioxidant properties, the pineal gland hormone melatonin has recently attracted the interest of various investigators as a multifunctional molecule. Melatonin has been shown to have beneficial effects in cardiovascular disorders including ischaemic heart disease and hypertension. However, its role in cardiovascular risk factors including obesity and other related metabolic abnormalities is not yet established, particularly in humans. New emerging data show that melatonin may play an important role in body weight regulation and energy metabolism. This review will address the role of melatonin in the MetS focusing on its effects in obesity, insulin resistance and leptin resistance. The overall findings suggest that melatonin should be exploited as a therapeutic tool to prevent or reverse the harmful effects of obesity and its related metabolic disorders.
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Human and rat pineal melatonin secretion decline with aging, whereas visceral fat and plasma insulin levels increase. Melatonin modulates fat metabolism in some mammalian species, so these aging-associated melatonin, fat and insulin changes could be functionally related. Accordingly, we investigated the effects of daily melatonin supplementation to male Sprague-Dawley rats, starting at middle age (10 months) and continuing into old age (22 months). Melatonin was added to the drinking water (92% of which was consumed at night) at a dosage (4 microg/ml) previously reported to attenuate the aging-associated decrease in survival rate in male rats, as well as at a 10-fold lower dosage. The higher dosage produced nocturnal plasma melatonin levels in middle-aged rats which were 15-fold higher than in young (4 months) rats; nocturnal plasma melatonin levels in middle-aged rats receiving the lower dosage were not significantly different from young or middle-aged controls. Relative (% of body wt) retroperitoneal and epididymal fat, as well as plasma insulin and leptin levels, were all significantly increased at middle age when compared to young rats. All were restored within 10 weeks to youthful (4 month) levels in response to both dosages of melatonin. Continued treatment until old age maintained suppression of visceral (retroperitoneal + epididymal) fat levels. Plasma corticosterone and total thyroxine (T4) levels were not significantly altered by aging or melatonin treatment. Plasma testosterone, insulin-like growth factor I (IGF-I) and total triiodothyronine (T3) decreased by middle age; these aging-associated decreases were not significantly altered by melatonin treatment. Thus, visceral fat, insulin and leptin responses to melatonin administration may be independent of marked changes in gonadal, thyroid, adrenal or somatotropin regulation. Since increased visceral fat is associated with increased insulin resistance, diabetes, and cardiovascular disease, these results suggest that appropriate melatonin supplementation may potentially provide prophylaxis or therapy for some prominent pathologies associated with aging.
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Glycemic control and prevention of secondary complications are the most important goals of using pharmacologic treatment of diabetes mellitus (DM). The inadequate responses to oral hypoglycemic agents may be attributed to inadequate postreceptor events even when insulin levels are quite sufficient, and associated with oxidative stress induced by long-term hyperglycemia. The administration of antioxidants such as melatonin and zinc may improve tissue responses to insulin and increase the efficacy of drugs, e.g. metformin, which act through this pathway. This project was designed to evaluate the effects of melatonin and zinc on the lipid profile and renal function in type 2 DM patients poorly controlled with metformin. A placebo-controlled, double-blind clinical trial was performed in which 46 type 2 diabetic patients were selected and allocated into three groups. These groups were treated with single daily oral doses of both 10 mg of melatonin and 50 mg of zinc acetate alone: 10 mg of melatonin and 50 mg of zinc acetate in addition to the regularly used metformin or placebo, given at bedtime for 90 days. Fasting lipid profiles and microalbuminuria (MAU) were measured before initiating the treatments (zero time) and after 30 and 90 days of treatment. Daily administration of melatonin and zinc improved the impaired lipid profile and decreased the level of MAU; the addition of this treatment regimen in combination with metformin improved the tissue responses to this oral hypoglycemic agent. In conclusion, the combination of melatonin and zinc acetate, when used alone or in combination with metformin, improves DM-related complications such as the impaired lipid profile and MAU in type 2 DM patients.
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This study evaluated the influence of melatonin on cholesterol absorption in rats fed on high cholesterol diet (HCD). HCD induced a remarkable increase in hepatic and plasma total cholesterol, plasma very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol, a decrease in high density lipoprotein (HDL) cholesterol and an elevation in triacylglyceride (TG) levels in plasma and in the liver. Melatonin suspension (10 mg/kg), specially prepared for this purpose, cholestyramine (230 mg/kg) and ezetimibe (145 microg/kg) were administered orally to the rats fed HCD for 30 days. Melatonin significantly reduced cholesterol absorption in rats fed on HCD and caused significant decreases in total cholesterol, TG, VLDL- and LDL-cholesterol in the plasma and contents of cholesterol and TG in the liver. The level of HDL cholesterol was significantly increased after melatonin. These results suggested that inhibition of cholesterol absorption caused by melatonin could be a mechanism contributing to the positive changes in plasma cholesterol, lipoprotein profile and the lipid contents in the liver.
Article
Background & aims: Melatonin may benefit diabetic people with coronary heart disease (CHD) through its beneficial effects on biomarkers of oxidative stress and cardio-metabolic risk. This investigation evaluated the effects of melatonin administration on metabolic status in diabetic patients with CHD. Methods: This randomized, double-blind, placebo-controlled trial was conducted and involved 60 diabetic patients with CHD. Subjects were randomly allocated into two groups to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 30) or placebo (n = 30) once a day for 12 weeks. Results: Compared with the placebo, melatonin supplementation resulted in significant increases in plasma glutathione (GSH) (+64.7 ± 105.7 vs. -11.1 ± 137.6 mmol/L, P = 0.02) and nitric oxide (NO) (+0.9 ± 4.7 vs. -3.3 ± 9.6 mmol/L, P = 0.03), and significant decreases in malondialdehyde (MDA) (-0.2 ± 0.3 vs. +0.1 ± 0.5 mmol/L, P = 0.007), protein carbonyl (PCO) (-0.12 ± 0.08 vs. +0.03 ± 0.07 mmol/mg protein, P < 0.001) and serum high sensitivity C-reactive protein (hs-CRP) levels (-1463.3 ± 2153.8 vs.+122.9 ± 1230.4 ng/mL, P = 0.001). In addition, taking melatonin, compared with the placebo, significantly reduced fasting plasma glucose (-29.4 ± 49.0 vs. -5.5 ± 32.4 mg/dL, P = 0.03), serum insulin concentrations (-2.2 ± 4.1 vs. +0.7 ± 4.2 mIU/mL, P = 0.008), homeostasis model of assessment-estimated insulin resistance (-1.0 ± 2.2 vs. +0.01 ± 1.6, P = 0.04), total-/HDL-cholesterol ratio (-0.18 ± 0.38 vs. +0.03 ± 0.35, P = 0.02) and systolic (-4.3±9.6 vs.+1.0±7.5mmHg, P=0.01) and diastolic blood pressure (-2.8±7.3 vs.-0.1±3.6 mmHg, P = 0.04). Melatonin treatment also significantly increased quantitative insulin sensitivity check index (+0.006 ± 0.01 vs. -0.004 ± 0.01, P = 0.01) and serum HDL-cholesterol (+2.6 ± 5.5 vs. -0.01 ± 4.4 mg/dL, P = 0.04). Supplementation with melatonin had no significant effect on other metabolic parameters. Conclusions: Overall, melatonin intake for 12 weeks to diabetic patients with CHD had beneficial effects on plasma GSH, NO, MDA, PCO, serum hs-CRP levels, glycemic control, HDL-cholesterol, total-/HDLcholesterol ratio, blood pressures and parameters of mental health. Registered under ClinicalTrials.gov Identifier no. http://www.irct.ir: IRCT2017051333941N1.
Article
Background & aims: Melatonin supplementation may be associated with blood lipids improvement; however, the current evidence from randomized controlled trials (RCTs) is inconsistent. The present study aimed to systematically review and analyze RCTs assessing the effects of melatonin supplementation on blood lipids. Methods: A comprehensive literature search in several database was performed up to January 2017. Quantitative data synthesis was performed using a fixed or random-effects model, with weight mean difference (WMD) and 95% confidence intervals (CI). Standard methods were used for assessment of heterogeneity, meta-regression, sensitivity analysis and publication bias. Results: A total of 8 RCTs were eligible. Meta-analysis suggested a significant association between melatonin supplementation and a reduction in triglycerides (WMD: -31.54 mg/dL, 95% CI: -50.71, -12.38, p = 0.001), and total cholesterol levels (WMD: -18.48 mg/dL, 95% CI: -35.33, -1.63, p = 0.032), while no significant effect on LDL-C (WMD: -2.37 mg/dL, 95% CI: -11.61, -6.86, p = 0.615) and HDL-C (WMD: 1.28 mg/dL, 95% CI: -0.66, 3.23, p = 0.197) was found. In sub-group analysis, a significant decrease in triglycerides was found at doses ≥8 mg/d and when trials last ≥8 weeks. In addition, a significant decrease of total cholesterol was found at doses ≥8 mg/d and when total cholesterol baseline levels were ≥200 mg/dL. Conclusions: Melatonin supplementation has significant effects on triglycerides and total cholesterol levels, which was more evident in higher dose and longer duration and also in a higher concentration of cholesterol levels. Further studies are required to determine the benefits of melatonin on lipid profile.
Article
Pineal melatonin secretion declines with aging, whereas visceral fat, plasma insulin, and plasma leptin tend to increase. We have previously demonstrated that daily melatonin administration at middle age suppressed male rat intraabdominal visceral fat, plasma leptin, and plasma insulin to youthful levels; the current study was designed to begin investigating mechanisms that mediate these responses. Melatonin (0.4 μg/ml) or vehicle was administered in the drinking water of 10-month-old male Sprague Dawley rats (18/treatment) for 12 weeks. Half (9/treatment) were then killed, and the other half were submitted to cross-over treatment for an additional 12 weeks. Twelve weeks of melatonin treatment decreased (P < 0.05) body weight (BW; by 7% relative to controls), relative intraabdominal adiposity (by 16%), plasma leptin (by 33%), and plasma insulin (by 25%) while increasing (P < 0.05) locomotor activity (by 19%), core body temperature (by 0.5 C), and morning plasma corticosterone (by 154%), restoring each of ...
Article
Smoking is one of the most harmful lifestyles in the world. Very few studies have investigated the effects of melatonin in smoke-induced vascular injury. This study was designed to investigate whether melatonin could protect rats and humans from smoke-induced vascular injury. 32 male rats and a double-blind randomized controlled trial (RCT) containing 63 participants formed the subjects of this study. In rats, 10mg/kg of melatonin was intraperitoneally injected. Blood samples and abdominal artery were harvested 2 weeks later. Melatonin decreased the expression of platelet endothelial cell adhesion molecule-1 (CD31), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelin-1 (ET-1) compared with the smoke exposed group (P < 0.05), whereas endothelial nitric oxide synthase (eNOS), nuclear erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO-1), catalytic glutamate cysteine ligase (GCLC) and heme oxygenase-1 (HO-1) recovered markedly (P < 0.05). In humans, 3 mg/day of melatonin was taken orally by the participants. Blood samples were drawn at baseline and after 2 weeks of treatment. Compared with the oral placebo group, melatonin decreased the concentration of fibrinogen (Fbg) (P = 0.04) and free fatty acids (FFA) (P = 0.04) in smokers, along with the decreased expression of ICAM-1, VCAM-1 and ET-1 (P = 0.004, P = 0.001, P < 0.0001, respectively). In contrast, Nrf2 and HO-1 expression were markedly increased (P = 0.0001, P = 0.0049, respectively) after smokers took melatonin orally. In summary, our present data suggests that melatonin could ameliorate smoke-induced vascular injury. This article is protected by copyright. All rights reserved.
Article
Frequent mood and sleep disorders and increased appetite leading to obesity are observed in postmenopausal women. Due to the limitations of hormone replacement therapy the researchers look for other treatment regimes. The aim of the study was to evaluate the efficacy of fluoxetine and melatonin in the treatment of these disorders. The study included 64 overweight postmenopausal women, aged 54 - 65 years, with increased appetite. They were randomly assigned in 2 groups. In group I (n = 30) fluoxetine (20 mg in the morning) and placebo (in the evening) were administered for 24 weeks. Group II (n = 34) received fluoxetine (20 mg in the morning) and melatonin (5 mg in the evening) in the same period of time. Hamilton anxiety rating scale (HARS), Beck depression scale (BDI), the insomnia severity index (ISI) and body mass index (BMI) were used to assess the health status and the treatment efficacy. After 24 weeks, comparable and statistically significant reduction in the level of anxiety and depression was obtained in both groups. In group I, the ISI decreased from 14.9 ± 2.5 points to 10.9 ± 1.9 points (P < 0.05) and in group II from 15.8 ± 2.4 points to 7.7 ± 1.5 points (P < 0.001). In group I no reduction in BMI was achieved whereas in group II this index decreased from 30.9 ± 3.1 to 26.3 ± 3.2 (P < 0.05). We conclude that combined administration of fluoxetine and melatonin was useful option to treat mood, sleep and appetite disorders in postmenopausal women.
Article
Improving the world health has resulted in increasing some kind of debilitating diseases. Among these debilitating diseases, the type 2 diabetes is one of the major concerns. In the recent years, new treatment options such as herbal products have emerged to improve glycemic control in these patients. However, the efficacy and safety of these new remedies are still a concern. Recent updates prove benefit of some herbal medicines like Citrullus Colocynthis, Silybum marianum, Plantago ovata, Teucrium polium, Vaccinium myrtillus, Urtica dioica, Medicago sativa, Punica granatum, Panax ginseng, Aloe vera, Allium sativum, Satureja khuzestanica and Trigonella foenum-graecum. Although, animal studies seem complete in demonstrating benefit of these medicines but clinical trials are not complete yet. Standardization of genus and type of the plant, higher sample size trials to specify the dosage and time treatment, or synergistic effects when used in mixtures with other herbs/drugs and profiling adverse effects/toxicities are the issues that should be taken into account in future. The constituents of these medicinal herbs should be targeted for new anti-diabetic drugs.
Article
Unlabelled: We aimed to determine the efficacy of melatonin 3 mg/day in prevention of olanzapine-induced metabolic side-effects. In a randomized double-blind placebo-controlled study, 48 patients with first-episode schizophrenia who were eligible for olanzapine treatment, were randomly assigned to olanzapine plus either melatonin 3 mg/day or matched placebo for eight weeks. Anthropometric and metabolic parameters as well as psychiatric symptoms using The Positive and Negative Syndrome Scale (PANSS) were assessed at baseline, week 4, and 8. Primary outcome measure was the change from baseline in weight at week 8. Data were analyzed using t-test, Mann-Whitney U test, and mixed-effects model. Thirty-six patients had at least one post-baseline measurement. At week eight, melatonin was associated with significantly less weight gain [mean difference (MD) = 3.2 kg, P = 0.023], increase in waist circumference [MD = 2.83 cm, P = 0.041] and triglyceride concentration [MD = 62 mg/dl, P = 0.090 (nearly significant)] than the placebo. Changes in cholesterol, insulin, and blood sugar concentrations did not differ significantly between the two groups. Patients in the melatonin group experienced significantly more reduction in their PANSS scores [MD = 12.9 points, P = 0.014] than the placebo group. No serious adverse events were reported. To summarize, in patients treated with olanzapine, short-term melatonin treatment attenuates weight gain, abdominal obesity, and hypertriglyceridemia. It might also provide additional benefit for treatment of psychosis. The study was registered in the ClinicalTrials.gov ( Registration number: NCT01593774).
Article
Metabolic syndrome is characterised by symptoms of obesity, insulin resistance, hypertension, dyslipidemia and diabetes mellitus. The pathophysiological mechanisms involved in MetS are complex and involve dysregulation of many biochemical and physiological regulatory mechanisms of the body. Elevated levels of low density lipoproteins like VLDL, and LDL with reduction of HDL seen in patients with MetS contribute to atherogenic dyslipedemia. Melatonin has been suggested to be effective in improving MetS through its anti-hyperlipidemic action .Melatonin reduced both adiposity, and body weight in experimental animal studies and also attenuated weight gain and obesity induced metabolic alterations and this effect of melatonin is attributed to its anti-oxidative effects. Melatonin administration has been shown to inhibit insulin release by acting through both MT1and MT2 melatonin receptors present in pancreatic β-cells. Melatonin also increased insulin sensitivity and glucose tolerance in animals fed with either high fat or high sucrose diet .Melatonin exerts most of its beneficial actions by acting through MT1 and MT2 melatonin receptors present in various tissues of the body and some of the metabolic actions of melatonin have been blocked by melatonin antagonist like luzindole. Ramelteon,the newly available melatonin agonist will have also more promising role in the control of MetS. Numbers of patents are available with regard to treatment of MetS. Drug related to antidepressant fluoxetine is used for treatment of MetS (US patent No. 2008001400450). Antioxidants like S adenosylmethionine, vitamin-E, and vitamin C have been found beneficial in treating Mets (US patent No. 8063024). Melatonin being a powerful antioxidant will have a promising role in treating patients with metabolic syndrome.
Article
Dyslipidemia and following atherosclerosis as a chronic affection remain one major cause of death all over the world. Given multiple reports on positive effects of melatonin on dyslipidemia, there is a need for reviewing all these studies in order to reach a convincing conclusion. Towards this goal, we have reviewed all previous investigations on use of melatonin in dyslipidemia found from PubMed, Cochrane, Google Scholar, Scopus and web of Science up to January 2012. Of the publications identified in the initial database, 11 clinical trials and 43 nonclinical trials (18 in vitro and 25 animal studies) were included and reviewed. Most of the results reveal the potency of melatonin as an antioxidant in preventing lipid peroxidation through different mechanisms and therefore, improving the lipid profile. Melatonin has anti-inflammatory and antioxidative effects, neutralizes free radicals, increases antioxidative enzymes and glutathione levels, prevents electron leakage from the mitochondrial respiratory chain, acts synergistically with vitamin C, E and glutathione, reduces levels of pro-inflammatory cytokines and therefore prevents Low-density Lipoprotein (LDL) oxidation and decreases lipid peroxidation. The results indicate a need for further studies on safety/efficacy measures if melatonin was used in long-term.
Article
Experimental studies have proven that melatonin has many beneficial pleiotropic actions. The aim of this study was to assess melatonin efficacy in patients with metabolic syndrome (MS). The study included 33 healthy volunteers (who were not treated with melatonin) and 30 patients with MS, who did not respond to 3-month lifestyle modification. Patients with MS were treated with melatonin (5 mg/day, 2 hr before bedtime) for 2 months. The following parameters were studied: systolic and diastolic blood pressure (SBP, DBP), levels of glucose, serum lipids, C-reactive protein, fibrinogen, activities of antioxidative enzymes: catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), thiobarbituric acid reactive substrates (TBARS). After 2-month therapy in comparison with baseline, the following significant changes were measured: systolic blood pressure (132.8±9.8 versus 120.5±11.0 mmHg, P<0.001), DBP (81.7±8.8 versus 75±7.4 mmHg, P<0.01), low-density lipoprotein cholesterol (LDL-C) (149.7±26.4 versus 139.9±30.2 mg/dL, P<0.05), TBARS (0.5±0.2 versus 0.4±0.1 μm/gHb, P<0.01), and CAT (245.9±46.9 versus 276.8±39.4 U/gHb). Melatonin administered for 2 months significantly improved antioxidative defense (increase in CAT activity, decrease in TBARS level) and lipid profile (decrease in LDL-C), and lowered blood pressure. We conclude that melatonin therapy may be of benefit for patients with MS, particularly with arterial hypertension. Further studies with higher doses of melatonin or prolonged supplementation are awaited.
Article
The study objective was to investigate the effects of melatonin on obesity and obesity-associated systolic hypertension and dyslipidemia in young male Zucker diabetic fatty (ZDF) rats, an experimental model of the metabolic syndrome. ZDF rats (n=30) and lean littermates (ZL) (n=30) were used. At 6wk of age, both lean and fatty animals were subdivided into three groups (n=10): naive (N), vehicle-treated (V), and melatonin-treated (M) (10mg/kg/day) for 6wk. Vehicle and melatonin were added to the drinking water. Melatonin reduced mean weight gain (51±2/100g BW) versus N-ZDF group (58±3, P<0.05) without food intake differences. M-ZDF rats showed an apparent reduction in systolic hypertension that proved not to be statistically significant, and a significant improvement in dyslipidemia, with a reduction in hypertriglyceridemia from 580±40 to 420.6±40.9mg/dL (P<0.01). Melatonin raised high-density-lipoprotein (HDL) cholesterol in ZDF (from 81.6±4.9 to 103.1±4.5mg/dL, P<0.01) and ZL rats (from 62.8±4.8 to 73.5±4.8mg/dL, P<0.05) and significantly reduced low-density-lipoprotein (LDL) cholesterol in ZDF rats from 5.20±0.4 to 4.14±0.3 mg/dL (P<0.05) but had no effect on total cholesterol levels. To our knowledge, this is the first evidence of a positive effect of melatonin on overweight and lipid pattern of obese Zucker diabetic rats, supporting the proposition that melatonin administration may ameliorate overweight and lipid metabolism in humans. Because these benefits occurred in youth, before advanced metabolic and vascular complications, melatonin might help to prevent cardiovascular disease associated with obesity and dyslipidemia.
Article
The present study was designed to investigate the cardioprotective effect of melatonin against isoproterenol induced myocardial infarction in rats by studying myocyte injury markers, antioxidant defense system, serum and heart lipid profile, inflammatory markers, electrocardiographic and histopathological changes. Male Sprague Dawley (SD) rats were randomly divided into four groups, namely control, melatonin, isoproterenol and melatonin+isoproterenol treated group. Melatonin treatment group received melatonin (10mg/kg/day, i.p.) for 7days. Myocardial infarction in rats was induced by isoproterenol administration (150mg/kg, s.c.) at an interval of 24h on 6th and 7th day. On 8th day ECG, gravimetric, biochemical and histopathological parameters were assessed. Isoproterenol administration showed changes in ECG pattern, including ST-segment elevation (diagnostic of myocardial infarction) increase in the serum levels of cardiac injury markers (creatine kinase-MB, lactate dehydrogenase, aspartate transaminase and alanine transaminase), decreased antioxidant defense system in the heart and altered lipid profile in the serum and heart. Isoproterenol administration also resulted in release of inflammatory markers and neutrophil infiltration along with histopathological changes. Melatonin pre-co-treatment prevented almost all the parameters of isoproterenol induced myocardial infarction in rats. The above finding was confirmed by the histopathological examination. In the baseline group (melatonin alone treated group) no significant change was observed. Results of the present study suggest that melatonin has a significant effect on the protection of the heart against isoproterenol induced myocardial infarction through maintaining endogenous antioxidant enzyme activities.
Article
Melatonin is an evolutionarily conserved molecule that serves a time-keeping function in various species. In vertebrates, melatonin is produced predominantly by the pineal gland with a marked circadian rhythm that is governed by the central circadian pacemaker (biological clock) in the suprachiasmatic nuclei of the hypothalamus. High levels of melatonin are normally found at night, and low levels are seen during daylight hours. As a consequence, melatonin has been called the "darkness hormone". This review surveys the current state of knowledge regarding the regulation of melatonin synthesis, receptor expression, and function. In particular, it addresses the physiological, pathological, and therapeutic aspects of melatonin in humans, with an emphasis on biological rhythms.
Article
There is some indirect evidence that the pineal hormone melatonin can suppress plasma levels of cholesterol in hypercholesterolemic rats. We have examined the effects of the hormone on cellular cholesterol metabolism in freshly isolated human mononuclear leukocytes. Incubation of cells for up to 20 h in a lipid-free medium resulted in an increase in the rate of cholesterol synthesis from [14C]acetate and the high affinity accumulation and degradation of [125I]labeled low density lipoprotein (LDL). Addition of melatonin in increasing concentrations to the incubation medium at zero time inhibited cholesterol synthesis and the specific accumulation and degradation of [125I]labeled LDL; at a concentration of 100 microM, the inhibitions were 38%, 42%, and 48%, respectively. Similar results were obtained using [14C]mevalonate as precursor. Fatty acid synthesis was not altered under these conditions. In contrast to cholesterol, the synthesis of the first cyclic compound lanosterol was not affected by the pineal hormone. These results implicate that melatonin inhibits this pathway between lanosterol and cholesterol. The action of melatonin on LDL receptor activity appeared to be mediated by a decrease in the number of LDL receptors and not by a change in binding affinity. Pharmacological characterization of the potential melatonin receptor site using several analogs like tryptamine, 5-hydroxytryptamine,N-acetyl-5-hydroxytryptamine, 5-methoxytryptamine, and 6-chloromelatonin indicated that the 5-methoxy group is indispensible for the hormone action on cholesterol synthesis. The data provide evidence that melatonin can modulate cholesterol metabolism in human cells.
Article
The purpose of this study was to investigate the effect of melatonin, at pharmacological doses, on serum lipids of rats fed with a hypercholesterolemic diet. Therefore, different groups of animals were fed with either the regular Sanders Chow diet or a diet enriched in cholesterol. Moreover, animals were treated with or without melatonin in the drinking water for 3 months. We show that melatonin treatment did not affect the levels of cholesterol or triglycerides in rats fed with a regular diet. However, the increase in total cholesterol and low-density lipoprotein (LDL)-cholesterol induced by a cholesterol-enriched diet was reduced significantly by melatonin administration. On the other hand, melatonin administration prevented the decrease in high-density lipoprotein (HDL)-cholesterol induced by the same diet. No differences in the levels of very low-density lipoprotein (VLDL)-cholesterol and triglycerides were found. We also found that melatonin administration slightly decreased serum uric, bilirubin and increased serum glucose levels. Other biochemical parameters, including total proteins, creatinine, urea, phosphorus, calcium, glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma-glutamyltranspeptidase (gamma-GT), acetyl cholinesterase (AcCho), and alkaline phosphatase (ALP) were not modified by melatonin treatment. Finally, lipid peroxidation (LPO) was studied in membranes of liver, brain, spleen, and heart as an index of membrane oxidative damage. Results show that hypercholesterolemic diet did not modify the LPO status in any of the tissues studied. However, chronic melatonin administration significantly decreased LPO. Results confirm that melatonin participates in the regulation of cholesterol metabolism and in the prevention of oxidative damage to membranes.
Article
The objective of this study was to investigate the effect of long-term melatonin administration on plasma levels of triglycerides, insulin and leptin, and on the fatty-acid metabolism of plasma and hepatic lipids in type 2 diabetic rats. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes mellitus, were divided into two groups: one untreated (n=6), and one implanted with time-releasing melatonin pellets (1.1 mg/day for 30 wk) under the abdominal skin (n=6). Age-matched Long-Evans Tokushima Otsuka (LETO) rats (n=6) were used as healthy controls. The untreated diabetic rats had the increased plasma levels of triglycerides, cholesterol, insulin and leptin at 35 wk, as compared with the healthy control rats (n=6). The diabetic rats also had augmented ratios of 20:3n-6/20:4n-6 fatty acids, owing to diminished activity of Delta-5 desaturase, an insulin-permissive enzyme, in the liver. Melatonin administration to OLETF rats reduced the hypertriglyceridemia (-39%, P < 0.05), hyperinsulinemia (-33%, P < 0.01) and hyperleptinemia (-43%, P < 0.01), and restored hepatic Delta-5 desaturase activity (148%, P < 0.005). This resulted in a return to normal ratios of 20:3n-6/20:4n-6 fatty acids in plasma and hepatic lipids. There was a significant correlation (r=0.64, P < 0.005) between plasma levels of insulin and the ratios of 20:3n-6/20:4n-6 in plasma phospholipids of all rats in the three groups. Thus, subcutaneous implantation of a melatonin-releasing pellet thus resulted in improved lipid metabolism in diabetic rats, probably through restored insulin resistance.
Article
This study was designed to investigate the effect of melatonin on the fatty acid composition of plasma and tissue lipids. Melatonin administration to rats fed with a standard diet only increased long-chain n-6 polyunsaturated fatty acids (PUFA) in total plasma lipids and liver phospholipids but induced significant changes in hypercholesterolemic rats. In plasma, palmitoleic and oleic acids increased and n-6 and n-3 PUFA decreased in hypercholesterolemic rats; theses changes were reversed by melatonin administration. The analysis of lipid fractions revealed that only the cholesteryl ester fraction was affected by melatonin. Histological studies of the carotid artery intima revealed the appearance, in hypercholesterolemic rats, of fatty streaks produced by a mass of foam cells covered by the endothelium and by a thin layer of mononucleated cells. These changes were prevented by melatonin. We conclude that long-term melatonin administration modifies the fatty acid composition of rat plasma and liver lipids and ameliorates the arterial fatty infiltration induced by cholesterol.
Article
In human beings, cardiovascular activity has a distinct circadian variation: Heart rate, blood pressure, and vascular tone decrease at night. Nocturnal cardiovascular blunting is at least partially linked to the autonomic activity and increased risk of cardiac and cerebral events. To assess whether decreased nocturnal melatonin synthesis and secretion in coronary artery disease (CAD), we investigated nocturnal secretion pattern of melatonin in patients with CAD and healthy subjects. The present study performed in 16 patients with angiographically documented CAD (aged 46-71 years) and in nine healthy controls (aged 36-66 years). Blood samples were collected every 2 h between 22:00 and 08:00 h. Melatonin levels were measured with a commercially available radioimmunoassay kit. We found large interindividual variation in the pattern of melatonin secretion in both groups. Patients with CAD secreted less nocturnal melatonin at 02:00, 04:00 and 08:00 h than control subjects (P=0.014, P=0.04 and P=0.025, respectively). Peak and Delta melatonin (peak-lowest melatonin) were found lower in patients with CAD (48.6 [19.1-75.4] vs. 131.4 [67.8-137.2] pg/ml, P=0.006 and 43 [10.5-68.5] vs. 107.6 [55.7-113.1] pg/ml, P=0.002, respectively). Peak time of melatonin secretion was observed earlier in patients with CAD (02:00 h [23:00-02:00 h] vs. 03:45 h [02:00-05:00 h], P=0.04). Our study provides useful and preliminary information about decreased nocturnal melatonin synthesis and release in patients with CAD might help physicians in managing these patients.
Article
The present study has been designed to determine melatonin levels in type 2 diabetic patients and test the relationship between the autonomic nervous system and melatonin dynamics. Thirty-six type 2 diabetic patients and 13 age-matched healthy subjects were recruited for the study. Circadian rhythm of melatonin secretion was assessed by measuring serum melatonin concentrations between 02:00-04:00 and 16:00-18:00 hr. Melatonin dynamics were re-evaluated with respect to autonomic nervous system in diabetic patients with autonomic neuropathy who were diagnosed by the cardiovascular reflex tests, heart rate variability (HRV), and 24-hr blood pressure monitoring. Nocturnal melatonin levels and the nocturnal melatonin surge were low in the diabetic group (P = 0.027 and 0.008 respectively). Patients with autonomic neuropathy revealed decreased melatonin levels both at night and during day when compared with healthy controls (P < 0.001 and 0.004 respectively) while the melatonin dynamics were similar to controls in patients without autonomic neuropathy. Nocturnal melatonin level was positively correlated with nocturnal high and low frequency components of HRV (P = 0.005 and 0.011 respectively) and systolic and diastolic blood pressures at night (P = 0.002 and 0.004 respectively) in patients with autonomic neuropathy. We found a negative correlation between nocturnal melatonin levels and the degree of systolic blood pressure decrease at night (r = -0.478, P = 0.045). As a conclusion this study has shown that circadian rhythm of melatonin secretion is blunted in type 2 diabetic patients and there is a complex relationship between various components of autonomic nervous system and melatonin secretion at night. Among the patients with autonomic neuropathy those with more preserved HRV and the systolic nondippers (<10% reduction in blood pressure during the night relative to daytime values) have more pronounced melatonin surge at night.
Article
Obesity and its associated metabolic pathologies are the most common and detrimental diseases, affecting over 50% of the adult population. Our knowledge about the protective effects of melatonin against high-fat diet (HFD)-induced obesity is still marginal. In this investigation, we hypothesized that melatonin can minimize the metabolic pathologies and morphological changes associated with obesity in animals receiving an HFD. To examine these effects, and to test our hypothesis, an animal model formed of male Boscat white rabbits was established. The animals were divided into three groups: (i) a control group fed regular diet; (ii) an obesity group fed an HFD for 12 weeks; and (iii) a treated group fed HFD for 12 weeks and then treated with melatonin for 4 weeks. The animals were killed and their serum and tissues were evaluated for: (i) lipid profile (cholesterol, triglycerides and low-density lipoprotein) and glucose; (ii) antioxidant enzyme (serum glutathione peroxidase, GSH-PX); and (iii) fatty changes (liver, kidney and blood vessels). Compared with the control group, intake of HFD (obesity group) was associated with: (i) a statistically significant increase in blood pressure, heart rate, sympathetic nerve activity, body weight, food consumption, serum lipids, blood glucose levels and atherogenic index; (ii) decreased level of GSH-PX and high-density lipoprotein (HDL); and (iii) fatty changes in the liver and kidney as well as atheromatous changes in the blood vessels. Compared with the obesity group, intake of melatonin (treated group) was associated with: (i) a statistically significant decrease in blood pressure, heart rate, sympathetic nerve activity, body weight, food consumption, serum lipids, blood glucose levels and atherogenic index; (ii) increased level of GSH-PX and HDL; and (iii) disappearance of fatty changes in the liver and kidney as well as atheromatous changes in the blood vessels. The administration of melatonin reduced the metabolic pathologies associated with the intake of HFD, suggesting a protective role. Although the underlying mechanisms are unclear, they may include its antioxidant and receptor-mediated effects. The clinical ramifications of these effects await further investigations.
Article
A growing number of reports demonstrate that a pro-inflammatory and oxidative condition is related to the pathogenesis and the progression of endotoxin-induced septic shock and that antioxidants may have therapeutic potential in lipopolysaccharide (LPS)-induced sepsis. Melatonin has been shown to possess potent antioxidant properties in several models of inflammation in mice and rats. In the present study we focused on the possible protective mechanism of melatonin in preventing gastrointestinal (GI) disturbances induced by LPS in mice. In fact, mice treated with LPS showed a reduced gastric emptying of solid beads. Also the geometric center, representing the relative distribution of the solid beads throughout the entire GI tract, was significantly reduced in LPS-treated mice confirming that sepsis leads to a disturbed GI motility in mice. Melatonin completely reversed the LPS-induced motility disturbance. This beneficial effect of melatonin is associated with a reduction in lipid peroxidation, MAPK activation, NF-kappaB activation, iNOS transcription and expression and nitrite production in intestinal tissue from septic mice. These results demonstrate that melatonin prevents the LPS-induced GI disturbances in mice switching off the pro-oxidant pathways induced by the endotoxin. Therefore, it is reasonable to propose melatonin as a molecule with therapeutic potential for the treatment of systemic inflammation by interfering at the earliest steps of activation of the oxidative and pro-inflammatory cascade.
Article
The purpose of this study was to investigate the effects of melatonin on lipid metabolism in peri- and postmenopausal women. Forty-six women were enrolled in these studies. The relationship between night-time serum melatonin levels and serum total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol was investigated in 36 women. Night-time serum melatonin levels had a negative correlation with serum total cholesterol and LDL-cholesterol, and a loose positive correlation with HDL-cholesterol. To examine the effects of exogenous melatonin on lipid metabolism, serum levels of total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides were determined in 10 women before the onset of therapy and after 1 month of oral melatonin administration (1 mg melatonin daily). Melatonin administration significantly increased the serum levels of HDL-cholesterol. These results show that melatonin may influence cholesterol metabolism and suggest that the melatonin administration may become a new medical application for improvement of lipid metabolism and prevention of cardiovascular disease in peri- and postmenopausal women.
Article
To estimate the overall prevalence and absolute burden of overweight and obesity in the world and in various regions in 2005 and to project the global burden in 2030. Pooling analysis. We identified sex- and age-specific prevalence of overweight and obesity in representative population samples from 106 countries, which cover approximately 88% of the world population, using MEDLINE and other computerized databases, supplemented by a manual search of references from retrieved articles. Sex- and age-specific prevalence of overweight and obesity were applied to the 2005 population to estimate the numbers of overweight and obese individuals in each country, each world region and the entire world. In addition, the prevalence, with and without adjusting for secular trends, were applied to the 2030 population projections to forecast the number of overweight and obese individuals in 2030. Overall, 23.2% (95% confidence interval 22.8-23.5%) of the world's adult population in 2005 was overweight (24.0% in men (23.4-24.5%) and 22.4% in women (21.9-22.9%)), and 9.8% (9.6-10.0%) was obese (7.7% in men (7.4-7.9%) and 11.9% in women (11.6-12.2%)). The estimated total numbers of overweight and obese adults in 2005 were 937 million (922-951 million) and 396 million (388-405 million), respectively. By 2030, the respective number of overweight and obese adults was projected to be 1.35 billion and 573 million individuals without adjusting for secular trends. If recent secular trends continue unabated, the absolute numbers were projected to total 2.16 billion overweight and 1.12 billion obese individuals. Overweight and obesity are important clinical and public health burdens worldwide. National programs for the prevention and treatment of overweight, obesity and related comorbidities and mortalities should be a public health priority.
Ursolic acid in experimental models and human subjects: potential as an anti-obesity/overweight treatment?
  • S J Felizola
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Melatonin and metabolic regulation: a review
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