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1.
Comparison of IVF and IVM outcomes in the same patient treated with a modified IVM protocol along with an oocytes-maturing system containing melatonin: A pilot study.
Li, X, Mu, Y, Elshewy, N, Ding, D, Zou, H, Chen, B, Chen, C, Wei, Z, Cao, Y, Zhou, P, et al
Life sciences. 2021;:118706
Abstract
AIM: To compare embryonic developmental competence and clinical outcomes of oocytes matured in vivo (IVF oocytes) and those matured in vitro (IVM oocytes) from the same IVM/IVF cycles, and to analyze the clinical efficiency of a melatonin-supplemented in vitro maturation system combined with a modified IVM/IVF protocol. MAIN METHODS We randomly recruited 22 patients undergoing IVM/IVF treatment protocol in our medical centre. The fertilization, cleavage and blastocyst formation rates, as well as clinical pregnancy, implantation and live birth/ongoing pregnancy rates were analysed and compared between IVF and IVM oocytes. We evaluated mitochondrial function indicators by fluorescence staining and confocal microscopy, including mitochondrial membrane potential, reactive oxygen species and calcium (Ca2+) levels in 15 IVF and 15 IVM oocytes. KEY FINDINGS There were no significant differences in fertilization or blastocyst formation rates between the IVF and IVM groups, whereas the cleavage rate was significantly higher in the IVF versus IVM group (100% vs 93.4 ± 10.9%, p = 0.03). There were no significant differences in the clinical pregnancy, implantation or live birth/ongoing pregnancy rates between the two groups. The cumulative clinical pregnancy and ongoing pregnancy/live birth rate per pick-up oocyte in the IVM/IVF treatment cycles were 68.2% (15/22) and 54.5% (12/22), respectively. The reactive oxygen species and Ca2+ levels were significantly increased, and mitochondrial membrane potential was significantly decreased, in IVM compared with IVF oocytes. SIGNIFICANCE The modified IVM/IVF protocol can be effectively applied to the treatment of some indicated patients and achieve ideal clinical outcomes, even though the developmental potential of IVM oocytes may not be as high as IVF oocytes.
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2.
Melatonin supplementation and the effects on clinical and metabolic status in Parkinson's disease: A randomized, double-blind, placebo-controlled trial.
Daneshvar Kakhaki, R, Ostadmohammadi, V, Kouchaki, E, Aghadavod, E, Bahmani, F, Tamtaji, OR, J Reiter, R, Mansournia, MA, Asemi, Z
Clinical neurology and neurosurgery. 2020;:105878
Abstract
OBJECTIVE This study was performed to evaluate the impact of melatonin supplementation on clinical and metabolic profiles in people with Parkinson's disease (PD). METHODS This randomized, double-blind, placebo-controlled clinical trial was conducted among 60 patients with PD. Participants were randomly divided into two groups to intake either 10 mg melatonin (two melatonin capsules, 5 mg each) (n = 30) or placebo (n = 30) once a day, 1 h before bedtime for 12 weeks. RESULTS Melatonin supplementation significantly reduced the Unified Parkinson's Disease Rating Scale (UPDRS) part I score (β -2.33; 95% CI, -3.57, -1.09; P < 0.001), Pittsburgh Sleep Quality Index (PSQI) (β -1.82; 95% CI, -3.36, -0.27; P = 0.02), Beck Depression Inventory (BDI) (β -3.32; 95% CI, -5.23, -1.41; P = 0.001) and Beck Anxiety Inventory (BAI) (β -2.22; 95% CI, -3.84, -0.60; P = 0.008) compared with the placebo treatment. Compared with the placebo, melatonin supplementation resulted in a significant reduction in serum high sensitivity C-reactive protein (hs-CRP) (β -0.94 mg/L; 95% CI, -1.55, -0.32; P = 0.003) and a significant elevation in plasma total antioxidant capacity (TAC) (β 108.09 mmol/L; 95% CI, 78.21, 137.97; P < 0.001) and total glutathione (GSH) levels (β 77.08 μmol/L; 95% CI, 44.29, 109.86; P < 0.001). Additionally, consuming melatonin significantly decreased serum insulin levels (β -1.79 μIU/mL; 95% CI, -3.12, -0.46; P = 0.009), homeostasis model of assessment-insulin resistance (HOMA-IR) (β -0.47; 95% CI, -0.80, -0.13; P = 0.007), total- (β -13.16 mg/dL; 95% CI, -25.14, -1.17; P = 0.03) and LDL- (β -10.44 mg/dL; 95% CI, -20.55, -0.34; P = 0.04) compared with the placebo. CONCLUSIONS Overall, melatonin supplementation for 12 weeks to patients with PD had favorable effects on the UPDRS part I score, PSQI, BDI, BAI, hs-CRP, TAC, GSH, insulin levels, HOMA-IR, total-, LDL-cholesterol, and gene expression of TNF-α, PPAR-γ and LDLR, but did not affect other metabolic profiles.
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3.
The effect of melatonin on treatment of patients with non-alcoholic fatty liver disease: a randomized double blind clinical trial.
Bahrami, M, Cheraghpour, M, Jafarirad, S, Alavinejad, P, Asadi, F, Hekmatdoost, A, Mohammadi, M, Yari, Z
Complementary therapies in medicine. 2020;:102452
Abstract
OBJECTIVES Many factors implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) are including oxidative stress, insulin resistance and abnormal production of adipokines. The aim of this clinical trial was to evaluate the effect of melatonin supplement on some important biochemical markers and signs related to NAFLD. DESIGN A randomized double-blind, placebo-controlled, clinical trial. SETTING Twenty-four participants in the melatonin group and 21 participants in the placebo group completed the study. INTERVENTION Participants received 6 mg melatonin or placebo daily, 1 h before bedtime. The intervention period was 12 weeks. MAIN OUTCOME MEASURES Anthropometric measurements, systolic and diastolic blood pressure, liver enzymes, high sensitive C‑reactive protein (hs-CRP), fatty liver grade, also leptin and adiponectin serum levels, were measured at the baseline and the end of intervention. RESULTS A significant improvement was observed in weight (p = 0.043), waist circumference (p = 0.027), abdominal circumference (p = 0.043), systolic (p = 0.039), and diastolic (p = 0.015) blood pressure, leptin serum levels (p = 0.032), hs-CRP (p = 0.024), alanine aminotransferase (p = 0.011), aspartate aminotransferase (p = 0.034), also the grade of fatty liver (p = 0.020) in melatonin treated group compared with the placebo. CONCLUSIONS Administration of 6 mg/day melatonin had improvement effect on many factors related to NAFLD such as liver enzymes, hs-CRP, anthropometric measurements, blood pressure, leptin serum levels and the grade of fatty liver.
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Use of nutritional supplements based on melatonin, tryptophan and vitamin B6 (Melamil Tripto®) in children with primary chronic headache, with or without sleep disorders: a pilot study.
Bravaccio, C, Terrone, G, Rizzo, R, Gulisano, M, Tosi, M, Curatolo, P, Emberti Gialloreti, L
Minerva pediatrica. 2020;(1):30-36
Abstract
BACKGROUND Headache is one of the main complaints in pediatric neurology. Exogenous melatonin has been shown to be useful and safe in improving sleep-wake cycles and sleep quality in children. Tryptophan as well plays a key role in sleep regulation. So far, no studies tried to analyze the effects of a combination of both melatonin and tryptophan in treating chronic headache in children affected also by night-time awakenings. METHODS Thirty-four children with a diagnosis of chronic headache (with or without sleep disorders) have been enrolled. The study was articulated in two steps: 1) each child was observed for one month without any intervention; 2) children have been then randomized into two groups: the "ME-group", which received the nutritional supplement melatonin for two months and the "MET-group", which received the nutritional supplements melatonin, tryptophan, and vitamin B6 for two months. RESULTS In terms of changes in number of headache events, responders in the ME-group were 91.7% and those in the MET-group were 66.7% (P=0.113). In terms of changes in number of night awakenings, in the ME group, mean number at baseline, after 30 days, and after 60 days were 3.6±3.2, 3.2±3.5, and 2.7±3.4 (P=0.495). In the MET group, mean number of night awakenings was 7.4±8.1, 4.0±4.4, and 3.3±2.9 (P=0.041). CONCLUSIONS Using either nutritional supplement for two months can help in decreasing the monthly number of headache episodes and night awakenings. The addition of tryptophan and vitamin B6 appears to have stronger influence on night awakenings reduction than melatonin only.
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Is dietary melatonin supplementation a viable adjunctive therapy for chronic periodontitis?-A randomized controlled clinical trial.
El-Sharkawy, H, Elmeadawy, S, Elshinnawi, U, Anees, M
Journal of periodontal research. 2019;(2):190-197
Abstract
BACKGROUND AND OBJECTIVE Melatonin is synthesized naturally by pineal gland and responsible for regulation of sleep/waking cycle. It showed appreciated anti-inflammatory and antioxidant properties. The aim of this randomized clinical trial (RCT) was to assess the additive effect of melatonin supplementation in insomniac individuals with generalized chronic periodontitis (gCP) after scaling and root planing (SRP). MATERIAL AND METHODS Seventy-four gCP patients with primary insomnia participated in this 6-month RCT and randomized into two groups. Melatonin group included 38 patients who were subjected to SRP with a 2-month regimen of 10 mg oral melatonin capsule once daily before bedtime. In the control group, SRP was performed for 36 participants provided with matching placebo capsules. The primary treatment outcome was the measurement of clinical attachment level gain (CAL gain) after 3 and 6 months of therapy, whereas the measurements of pocket depth reduction (PD reduction), bleeding on probing (BOP %), and the changes in salivary TNF-α levels and Athens insomnia scale (AIS) scores represented the secondary endpoints. RESULTS Melatonin group showed significantly greater CAL gain and PD reduction measurements compared to the control group at 3 and 6 months of therapy, P < 0.01. Likewise, salivary TNF-α levels and AIS scores were significantly lower in the melatonin group compared to placebo group. BOP% improved significantly in both groups without any difference. However, salivary TNF-α levels exhibited no correlation with other clinical variables in both melatonin and placebo groups. CONCLUSION Daily dietary 10 mg of melatonin supplementation might serve as a viable adjunct to SRP that yielded significantly greater CAL gain and PD reduction and lower salivary TNF-α levels and AIS scores in gCP patients with primary insomnia.
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The effects of melatonin supplementation on mental health, metabolic and genetic profiles in patients under methadone maintenance treatment.
Ghaderi, A, Banafshe, HR, Mirhosseini, N, Motmaen, M, Mehrzad, F, Bahmani, F, Aghadavod, E, Mansournia, MA, Reiter, RJ, Karimi, MA, et al
Addiction biology. 2019;(4):754-764
Abstract
This investigation was designed to determine the effect of melatonin supplementation on mental health parameters, metabolic and genetic profiles in patients under methadone maintenance treatment (MMT). This randomized, double-blind, placebo-controlled, clinical trial was conducted among 54 patients under MMT. Participants were randomly allocated to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 26) or placebo (n = 28) once a day, 1 hour before bedtime for 12 weeks. Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (β -4.08; 95 percent CI, -5.51, -2.65; P < 0.001), Beck Depression Inventory index (β -5.46; 95% CI, -8.92, -2.00; P = 0.003) and Beck Anxiety Inventory index (β -3.87; 95% CI, -5.96, -1.77; P = 0.001) and significantly increased International Index of Erectile Functions (β 5.59; 95% CI, 1.76, 9.42; P = 0.005) compared with the placebo. Subjects who received melatonin supplements had significantly lower serum insulin levels (β -2.53; 95% CI, -4.48, -0.59; P = 0.01), homeostasis model of assessment-insulin resistance (β -0.56; 95% CI, -1.03, -0.09; P = 0.01) and higher quantitative insulin sensitivity check index (β 0.01; 95% CI, 0.004, 0.02; P = 0.009) and HDL-cholesterol levels (β 3.71; 95% CI, 1.77, 5.64; P = 0.002) compared to placebo. Additionally, melatonin intake resulted in a significant reduction in serum high sensitivity C-reactive protein (β -0.15; 95% CI, -0.27, -0.02; P = 0.02), malondialdehyde (β -0.31; 95% CI, -0.57, -0.05; P = 0.02) and protein carbonyl (β -0.06; 95% CI, -0.09, -0.04; P < 0.001). This trial indicated that taking melatonin supplements for 12 weeks by patients under MMT had beneficial effects on their mental health metabolic profiles.
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7.
Melatonin Improves Erythropoietin Hyporesponsiveness via Suppression of Inflammation.
Hameed, EN, Hadi Al Tukmagi, HF, Allami, HCA
Reviews on recent clinical trials. 2019;(3):203-208
Abstract
BACKGROUND Inadequate response to Erythropoietin Stimulating Agents (ESA) despite using relatively larger doses regimen represents a potential risk factor of Cardiovascular (CV) related mortality in addition to health-care economic problems in anemic patients with Chronic Kidney Disease (CKD). Erythropoietin (EPO) hyporesponsiveness related to inflammation has been increased progressively. Melatonin is well known as a potent anti-inflammatory agent. Therefore, the current study was designed to evaluate whether melatonin could improve anemic patients response to EPO. METHODS This single controlled clinical study was carried out in 41 CKD patients with hemoglobin (Hb) levels less than 11g/dl divided randomly in a 1:1 ratio into 2 groups; treatment group who received 5mg melatonin plus their regular treatments and control group who received their regular treatments only. Hematological and iron status parameters include Hb level, serum iron (S. iron), Transferrin Saturation Ratio (TSAT) and serum ferritin (S. ferritin) in addition to inflammatory parameters that include tissue necrotic factor alfa (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) determined before and after 12 weeks of treatment. RESULTS Melatonin remarkably increases the Hb level with a significant increase in S. iron and TSAT compared to baseline. The elevation of S. iron and TSAT was significantly higher in the melatonin group. Additionally, all inflammatory markers estimated were reduced significantly by melatonin compared to base line and control group. CONCLUSION The results of the current study showed that melatonin has an advantageous effect on improving EPO response in anemic patients with CKD.
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Consumption of a 5-mg Melatonin Supplement Does Not Affect 32.2-km Cycling Time Trial Performance.
Brandenberger, KJ, Ingalls, CP, Rupp, JC, Doyle, JA
Journal of strength and conditioning research. 2018;(10):2872-2877
Abstract
Brandenberger, KJ, Ingalls, CP, Rupp, JC, and Doyle, JA. Consumption of a 5-mg melatonin supplement does not affect 32.2-km cycling time trial performance. J Strength Cond Res 32(10): 2872-2877, 2018-Some studies suggest that exogenous melatonin supplementation may improve athletic performance in hot humid environments because of its precooling effect. However, melatonin is also consumed as a sleep aid for its depressive effects on the central nervous system (CNS), which may hinder performance. Therefore, this study was conducted to determine whether consuming a 5-mg supplement of melatonin would affect performance in a laboratory-simulated 32.2-km cycling time trial. The time trial was conducted in a thermoneutral environment to separate CNS depressive effects of the melatonin from the cooling effects. Trained male subjects (n = 10; V[Combining Dot Above]O2max = 62.7 ± 6.3 ml·kg·min; age = 25.1 ± 4.0 years; mass = 69.9 ± 9.1 kg; height = 176.0 ± 7.1 cm) performed three 32.2-km time trials on an electronically braked cycle ergometer. The first trial was a familiarization. During the 2 experimental trials, subjects received in a random order either a placebo or a 5-mg melatonin supplement 15 minutes before exercise in a double-blind, crossover design. Variables were measured before exercise and at 8-km intervals. The mean 32.2-km time trial completion times for the melatonin (64.94 ± 5.95 minutes) and placebo (65.26 ± 6.85 minutes) trials were not different (p = 0.682). The mean time trial power output for the melatonin (190.4 ± 40.4 watts) and placebo (190.0 ± 45.7 watts) trials was not different (p = 0.927). Rectal temperature was not significantly different for melatonin compared with placebo (p = 0.827). These results suggest that a 5-mg melatonin supplement administered 15 minutes before exercise does not measurably impact the performance of a 32.2-km cycling time trial in a thermoneutral environment.
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Normalization of disrupted clock gene expression in males with tetraplegia: a crossover randomized placebo-controlled trial of melatonin supplementation.
Kostovski, E, Frigato, E, Savikj, M, Dahm, A, Sandset, PM, Mowinckel, MC, Skretting, G, Østerud, B, Bertolucci, C, Iversen, PO
Spinal cord. 2018;(11):1076-1083
Abstract
STUDY DESIGN Crossover double blind, randomized placebo-controlled trial. OBJECTIVES Circadian oscillators are located both in the brain and in peripheral organs. Melatonin, the main brain-derived hormone governing circadian variations, is highly associated with daylight patterns. However, in subjects with tetraplegia the melatonin levels are blunted. Here we studied peripheral oscillators in peripheral blood mononuclear cells (PBMCs) in males with tetraplegia by examining how exogenous melatonin may influence the expression of clock gene mRNAs. SETTING Sunnaas Rehabilitation Hospital, Nesoddtangen, Norway. METHODS Six males with tetraplegia received 2 mg of melatonin or placebo 4 days before the study period. We also included six able-bodied men sleeping or kept awake during the night. Plasma samples were collected four times during a 24-h period. The mRNA expression levels of the clock genes PER1, PER2, BMAL1, and REV-ERBα were quantified in PBMCs using quantitative RT-PCR. RESULTS The mRNA expression levels of PER-1 and -2 and REV-ERBα were increased at 04:00 h compared with the able-bodied controls (p < 0.05). Melatonin supplementation changed mRNA peak-time toward the time of supplementation. CONCLUSIONS Several peripheral clock genes displayed distorted expression levels in tetraplegia. Supplementation with melatonin changed the mRNA expression levels of these genes toward those observed among able-bodied. SPONSORSHIP Financial support was provided from the Throne Holst Foundation, Sunnaas Rehabilitation hospital and the University of Ferrara (FAR2016).
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The effects of melatonin administration on disease severity and sleep quality in children with atopic dermatitis: A randomized, double-blinded, placebo-controlled trial.
Taghavi Ardakani, A, Farrehi, M, Sharif, MR, Ostadmohammadi, V, Mirhosseini, N, Kheirkhah, D, Moosavi, SGA, Behnejad, M, Reiter, RJ, Asemi, Z
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2018;(8):834-840
Abstract
BACKGROUND The aim of this clinical trial was to determine the effects of melatonin administration on disease severity and sleep quality in children diagnosed with atopic dermatitis (AD). METHODS This randomized, double-blinded, placebo-controlled trial was conducted by recruiting 70 patients, aged 6-12 years, who had been diagnosed with AD. Study participants were randomly allocated into two intervention groups to receive either 6 mg/d melatonin supplements or placebo (n = 35 each group) for 6 weeks. Severity of disease was assessed using the scoring atopic dermatitis (SCORAD) and objective SCORAD indices. Sleep quality was evaluated by completing the Children's Sleep Habits Questionnaire (CSHQ). RESULTS Following 6 weeks of intervention, melatonin supplementation significantly improved SCORAD index (β -3.55; 95% CI, -6.11, -0.98; P = 0.007), objective SCORAD index (β -3.23; 95% CI, -5.08, -1.38; P = 0.001), serum total IgE levels (β -153.94 ku/L; 95% CI, -260.39, -47.49; P = 0.005), and CSHQ scores (β -2.55; 95% CI, -4.34, -0.75; P = 0.006). However, melatonin had no significant impact on pruritus scores, high-sensitivity C-reactive protein (hs-CRP), sleep-onset latency, total sleep time, weight, and BMI compared with placebo. CONCLUSIONS Overall, melatonin supplementation had beneficial effects on disease severity, serum total IgE levels, and CSHQ among children diagnosed with AD.