Melatonin (0.5mg)

OBJECTIVE: Melatonin and progesterone levels decline during the perimenopause. Both hormones inhibit estrogen action and endometrial cancer, but little is known about how they act in combination. Therefore, the interplay of progesterone (P4) and melatonin was investigated in intact female mice. STUDY DESIGN: Three P4 doses, low (25mg), mid (50mg), and high (100mg), combined with 0.5mg 17β-estradiol (E), were administered in the diet (per 1800kcal) for 30 days. Hormone therapy (HT) with the low P4 dose (estradiol/low progesterone replacement therapy (EPLRT)) was used to create an excess estrogen environment to mimic perimenopause. Half the mice were treated with melatonin (M) 15mg/L in the drinking water at night. RESULTS: The unbalanced EPLRT treatment increased estrogen-regulated responses. Specifically, mice treated with EPLRT had significantly higher levels of ovarian aromatase mRNA versus control, which was prevented in the presence of higher doses of P4 and/or the addition of melatonin. The number of days in estrus also increased in EPLRT-treated versus control mice with no change in the length or number of complete estrous cycles. Melatonin, combined with all doses of P4, increased the number of days spent in estrus, but not the length or number of estrous cycles compared to melatonin alone; however, two-way ANOVA revealed a significant interaction between melatonin and P4 dose for days in estrus and for number of cycles. Although none of the E2 and P4 combinations significantly affected uterine weight compared to control, melatonin addition to the low or mid P4 HT resulted in slightly higher uterine weights compared to melatonin-treated mice. Melatonin significantly increased uterine estrogen receptor alpha (ERα) and progesterone receptor A levels compared to control animals. HT, added in combination with melatonin, reduced ERα levels back to control levels, but PR levels remained elevated albeit intermediary to those achieved with melatonin alone. CONCLUSION: The findings that melatonin supplementation inhibits ovarian aromatase expression and increases uterine receptors in mice given an HT that mimics perimenopause may have important clinical applicatio

Melatonin, the major hormone produced by the pineal gland, has a number of functions in mammals, for example, its function as an anticonvulsant. Agmatine, a biogenic amine formed by decarboxylation of L-arginine by arginine decarboxylase, also has anticonvulsant effects. This study investigated the effect of the interaction of melatonin and agmatine on seizure susceptibility in the mouse model of pentylenetetrazole (PTZ)-induced clonic seizures. Further, the researchers investigated the involvement of melatonin receptors in this interaction using luzindole, a ML(1/2) receptor antagonist and prazosin, a ML(3) receptor antagonist. Melatonin, at 40 and 80 mg/kg, and agmatine, at 10 and 20mg/kg, exerted anticonvulsant effects. Luzindole, at 1.25 and 2.5mg/kg, or prazosin, at 0.5mg/kg, did not change the seizure threshold as compared with that of vehicle-treated mice. The anticonvulsant effect of melatonin (40 and 80 mg/kg) was prevented by luzindole (2.5mg/kg) (P<0.001) but not prazosin (0.5mg/kg), indicating the possible involvement of ML(1/2) receptors in the anticonvulsant effect of melatonin. Agmatine (5mg/kg) significantly increased the anticonvulsant effect of both the noneffective dose (20mg/kg) (P<0.05) and the effective dose (80 mg/kg) (P<0.001) of melatonin. Luzindole (2.5mg/kg), but not prazosin (0.5mg/kg), decreased the anticonvulsant effect of agmatine (20mg/kg) (P<0.05). Luzindole (2.5mg/kg), but not prazosin (0.5mg/kg), also decreased the seizure threshold when agmatine (5mg/kg) was administered before melatonin (20mg/kg); the decrease was significant compared with that of the group that received only agmatine and melatonin (P<0.001). In conclusion, melatonin and agmatine exhibit an additive effect in decreasing pentylenetetrazole-induced seizure threshold in mice, probably through ML(1/2) receptors.

Tryptophan (TRP), which plays an important role in immune system regulation, protein synthesis, serotonin (5-HT) and melatonin production, is a potent endogenous free radical scavenger and antioxidant. The aim of this work was to determine the efficacy of TRP in neuro-inflammation induced by systemic administration of lipopolysacharide (LPS, 20mg/kg) which promotes the synthesis of free radical (LPO: MDA and 4-HDA), and pro-inflammatory cytokine Interferon-γ (IFN-γ) in different brain regions (cerebral cortex and hippocampus) of rats. Experiments were performed on adult female, pregnant and lactating rats fed with a diet of TRP content (0.5mg/100g protein), cerebral cortex and hippocampus were evaluated for lipid peroxidation (LPO) products, nitrites, nitrates and plasmatic concentration of IFN-γ. LPO levels in LPS+TRP groups were significantly decreased than that obtained in the LPS group. However, there were no observed differences in plasmatic levels of nitrites and nitrates as well as IFN-γ, neither in the cerebral cortex or hippocampus. The TRP has protective effect in the oxidative damage in a model of endotoxic shock in the breading nurslings induced by the systemic administration of LPS, acting as a scavenger of free radicals. So, it can be proposed as an innocuous protector agent in the endotoxic shock process.

BACKGROUND: : Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination. Melatonin is a pineal hormone that plays a central part in regulating bodily rhythms and has been used as a drug to re-align them with the outside world. OBJECTIVES: : To assess the effectiveness of oral melatonin taken in different dosage regimens for alleviating jet-lag after air travel across several time zones. SEARCH STRATEGY: : We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and Science Citation Index electronically, and the journals 'Aviation, Space and Environmental Medicine' and 'Sleep' by hand. We searched citation lists of relevant studies for other relevant trials. We asked principal authors of relevant studies to tell us about unpublished trials. Reports of adverse events linked to melatonin use outside randomised trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly', MEDLINE, and the adverse drug reactions databases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration. SELECTION CRITERIA: : Randomised trials in airline passengers, airline staff or military personnel given oral melatonin, compared with placebo or other medication. Outcome measures should consist of subjective rating of jet-lag or related components, such as subjective wellbeing, daytime tiredness, onset and quality of sleep, psychological functioning, duration of return to normal, or indicators of circadian rhythms. DATA COLLECTION AND ANALYSIS: : Ten trials met the inclusion criteria. All compared melatonin with placebo; one in addition compared it with a hypnotic, zolpidem. Nine of the trials were of adequate quality to contribute to the assessment, one had a design fault and could not be used in the assessment. Reports of adverse events outside trials were found through MEDLINE, 'Reactions Weekly', and in the WHO UMC database. MAIN RESULTS: : Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from

BACKGROUND: Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination. Melatonin is a pineal hormone that plays a central part in regulating bodily rhythms and has been used as a drug to re-align them with the outside world. OBJECTIVES: To assess the effectiveness of oral melatonin taken in different dosage regimens for alleviating jet-lag after air travel across several time zones. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and Science Citation Index electronically, and the journals 'Aviation, Space and Environmental Medicine' and 'Sleep' by hand. We searched citation lists of relevant studies for other relevant trials. We asked principal authors of relevant studies to tell us about unpublished trials. Reports of adverse events linked to melatonin use outside randomised trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly', MEDLINE, and the adverse drug reactions databases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration. SELECTION CRITERIA: Randomised trials in airline passengers, airline staff or military personnel given oral melatonin, compared with placebo or other medication. Outcome measures should consist of subjective rating of jet-lag or related components, such as subjective wellbeing, daytime tiredness, onset and quality of sleep, psychological functioning, duration of return to normal, or indicators of circadian rhythms. DATA COLLECTION AND ANALYSIS: : Ten trials met the inclusion criteria. All compared melatonin with placebo; one in addition compared it with a hypnotic, zolpidem. Nine of the trials were of adequate quality to contribute to the assessment, one had a design fault and could not be used in the assessment. Reports of adverse events outside trials were found through MEDLINE, 'Reactions Weekly', and in the WHO UMC database. MAIN RESULTS: : Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from flights

Background/Objectives: Oxidative stress plays an important role in the pathophysiology of endometriosis, contributing to inflammation, immune dysregulation, and lesion progression. This has led to growing interest in antioxidant-based strategies as potential supportive interventions. Methods: A literature search was conducted using PubMed, Scopus, and Web of Science databases, covering studies published from database inception until the end of January 2026. The review focused on clinically relevant endpoints, including pain intensity, markers of inflammation and oxidative stress, reproductive parameters, and quality of life. Results: Among the analyzed interventions, the most consistent clinical effects were observed with melatonin, with randomized controlled trials indicating a moderate reduction in pain. N-acetylcysteine shows potentially beneficial effects; however, the available clinical data remain limited and heterogeneous. For other supplements, the evidence is inconsistent or insufficient to support clear clinical conclusions, and in many cases relies on indirect or mechanistic findings rather than well-established clinical outcomes. Conclusions: Current evidence does not support the use of non-mineral antioxidant supplements as standalone therapy for endometriosis. They may be considered as adjunctive strategies, although their clinical effectiveness remains uncertain and requires confirmation in well-designed randomized clinical trials.

This study aimed to evaluate the effects of melatonin supplementation on disease severity, sleep quality, and quality of life in adult patients with atopic dermatitis (AD). This study was designed as a randomized, double-blind, placebo-controlled clinical trial involving adult patients with mild to moderate AD. Eligible participants were randomly assigned to receive either a 10 mg melatonin tablet or a matching placebo once daily for 4 weeks. The primary outcome was the severity of AD, assessed by SCORAD index at baseline and after 4 weeks of supplementation. Secondary outcomes included the intensity of pain (NPRS), pruritus severity (Pruritus-NRS), sleep quality (ADSS), and quality of life (DLQI). Eighty patients completed the study. The mean age (Standard deviation) of the patients was 33.26 (12.57) years, and 32 patients (40%) were male. The SCORAD, Pruritus-NRS, 12-PSS, ADSS, and DLQI indices improved significantly (p-values of < 0.001, 0.006, 0.011, < 0.05, and 0.003, respectively) after 4 weeks of supplementation. However, melatonin supplementation did not improve the NPRS (p-value: 0.063). No patient reported an adverse effect throughout the study. Melatonin supplementation in adult patients with mild to moderate AD effectively improved disease severity, sleep quality, and quality of life, without any reported adverse effects. However, due to limitations of our study, further research is required to confirm these findings. © 2026 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

BACKGROUND/OBJECTIVES: Medicinal mushrooms have been gaining increasing attention as functional foods; however, scientific evidence from human studies remains limited. METHODS: In this study, 50 participants were randomly assigned to receive either Restake or a placebo. Psychological and physiological parameters were assessed at baseline, 6 weeks, and 12 weeks using validated tools, including the Pittsburgh Sleep Quality Index (PSQI), Visual Analog Scale for Fatigue (VAS-F), Multidimensional Fatigue Inventory (MFI), State-Trait Anxiety Inventory (STAI-S), Perceived Stress Scale (PSS), Hamilton Anxiety Scale (HAM-A), and Beck Depression Inventory (BDI). Serum biomarkers-cortisol, norepinephrine (NE), melatonin, adrenocorticotropic hormone (ACTH), and C-reactive protein (CRP)-were analyzed via ELISA. RESULTS: Anxiety, assessed by STAI-S and HAM-A, showed greater reductions in the Restake group at both 6 weeks (STAI-S: p = 0.025; HAM-A: p = 0.002) and 12 weeks (STAI-S: p = 0.011; HAM-A: p = 0.002). Depression (BDI) scores significantly decreased at 6 weeks (p < 0.001) and 12 weeks (p = 0.008). Fatigue levels showed significant reductions in general fatigue (p = 0.043), physical fatigue (p = 0.027), and mental fatigue (p = 0.043). Restake supplementation led to reductions in sleep quality scores (PSQI) at 6 weeks (p = 0.005) and 12 weeks (p < 0.001). Biomarker analysis revealed significant reductions (p < 0.001) in cortisol and ACTH levels and a decrease in CRP levels (p = 0.042). NE levels significantly (p = 0.033). Compared to the placebo group, Restake supplementation exhibited an increased morning melatonin trend after 12 weeks of intervention. CONCLUSIONS: Restake supplementation was well tolerated and effectively reduced psychological stress, fatigue, and improved sleep quality without adverse effects. © 2026 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.

Background/Objectives: There is no definitive consensus regarding the effects of melatonin on cardiometabolic risk factors (CMRFs). This systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) evaluated the impacts of melatonin supplementation on CMRFs, including anthropometric, lipid, glycemic, inflammatory, oxidative, and liver function parameters. Methods: A systematic search across multiple databases retrieved 63 eligible RCTs published up to October 2025. Results: This random-effects meta-analysis indicated that melatonin supplementation significantly reduced hip circumference (weighted mean difference (WMD): -1.18 cm, 95% confidence interval (CI): -2.28, -0.08), systolic blood pressure (WMD: -2.34 mmHg, 95% CI: -4.13, -0.55), fasting blood glucose (WMD: -11.63 mg/dL, 95% CI: -19.16, -4.10), low-density lipoprotein cholesterol (WMD: -6.28 mg/dL, 95% CI: -10.53, -2.03), total cholesterol (WMD: -6.97 mg/dL, 95% CI: -12.20, -1.74), C-reactive protein (WMD: -0.59 mg/L, 95% CI: -0.94, -0.23), malondialdehyde (WMD: -1.54 μmol/L, 95% CI: -2.07, -1.01), tumor necrosis factor-alpha (WMD: -1.61 pg/mL, 95% CI: -2.31, -0.90), interleukin-6 (WMD: -6.43 pg/mL, 95% CI: -10.72, -2.15), and alanine aminotransferase (WMD: -2.61 IU/L, 95% CI: -4.87, -0.34). Supplementation with melatonin substantially increased serum total antioxidant capacity (WMD: 0.15 mmol/L, 95% CI: 0.08, 0.22) and high-density lipoprotein cholesterol (WMD: 2.04 mg/dL, 95% CI: 0.50, 3.57). No significant effects of melatonin were observed on body weight, waist circumference, body fat percentage, body mass index, fasting insulin, homeostasis model assessment of insulin resistance, hemoglobin A1c, triglycerides, diastolic blood pressure, aspartate aminotransferase, or gamma-glutamyl transferase. Conclusions: Melatonin supplementation significantly ameliorated multiple CMRFs.

Background: Insomnia is prevalent and difficult to treat safely over the long term. Given the role of the microbiota-gut-brain axis in melatonin and hypothalamic-pituitary-adrenal (HPA) regulation, and preclinical evidence for Limosilactobacillus fermentum PS150, we evaluated whether a heat-treated formulation (HT-PS150) could improve sleep and modulate endocrine/circadian markers in adults with poor sleep. Methods: In a randomized, double-blind, placebo-controlled trial, 84 adults aged 20-60 years with PSQI ≥ 5 and ISI < 22 were assigned to receive either placebo or HT-PS150 for eight weeks. Outcomes included patient-reported sleep (PSQI, ISI), anxiety/depression (GAD-7, PHQ-9), quality of life (QLESQ-SF), gastrointestinal symptoms (VAS-GI), wrist actigraphy (Fitbit Inspire 3), and sleep-relevant biomarkers measured from urine, saliva, and/or blood samples (melatonin, cortisol, orexin, serotonin, GABA, and/or norepinephrine). Repeated measures were analyzed using generalized estimating equations. An exploratory proportional regulation analysis classified individual biomarker changes as up- or down-regulated and compared proportions between study arms. Per-protocol analyses required ≥80% compliance. Results: Improvements in the primary outcomes, PSQI and ISI, were observed over time in both groups, while no significant group × time interactions were detected. In exploratory proportional analyses, a higher proportion of participants in the HT-PS150 group exhibited up-regulated nocturnal melatonin secretion and improved daytime plasma orexin levels, as well as a tendency toward greater reductions in nocturnal salivary cortisol compared with placebo. In subgroup analyses with higher baseline insomnia severity (ISI ≥ 8), HT-PS150 was associated with greater improvements in PSQI (notably sleep duration and efficiency) and reduction in anxiety (GAD-7) upon post hoc testing. Conclusions: Although group mean scores on sleep symptom scales did not differ significantly in the full cohort, HT-PS150 appeared to modulate sleep-wake regulation by enhancing nocturnal melatonin secretion, attenuating HPA-axis activity, and stabilizing wakefulness. Clinical benefits were most ev

Difficulties falling and/or staying asleep affect over one quarter of adults in the United States. Current management strategies include prescription sleep aids. However, long-term use is associated with serious adverse effects. Therefore, natural alternative sleep aids that may provide safer and more effective relief of sleep disturbances are needed. In this randomized, triple-blind, placebo-controlled clinical trial, 80 healthy adults (n = 40 per group) with difficulties falling and/or staying asleep were supplemented with a standardized corn leaf extract (CLE) or placebo for 28 days. Objective (actigraphy with electroencephalogram) and subjective (Pittsburgh Sleep Quality Index) sleep measures, serum serotonin, plasma melatonin, and gamma-aminobutyric acid were assessed at baseline (Day 0), Day 14, and Day 28, and safety was assessed at screening and Day 28. Compared to placebo, participants supplemented with CLE demonstrated statistically significant increases in total sleep time (TST) and light sleep at Day 28 and improvements in REM sleep at both Days 14 and 28. Further, participants supplemented with CLE had significantly fewer sleep interruptions and shorter sleep onset latency at Day 14 with shorter wake after sleep onset (WASO) and higher sleep efficiency at Days 14 and 28. Post hoc analysis supported these findings with a significant increase of 35.7 min in non-REM sleep at Day 28 for participants supplemented with CLE compared to a decrease of 10.6 min for those on placebo. Supplementation with CLE was safe and well tolerated. Findings suggest CLE supplementation may improve sleep parameters in a healthy population with sleep difficulties. © 2026 KGK Science Inc. Food Science & Nutrition published by Wiley Periodicals LLC.

BACKGROUND: Endometriosis, a chronic inflammatory disorder, is a leading cause of pelvic pain and reduced quality of life in women, with oxidative stress implicated in its pathogenesis. While antioxidant supplementation has been proposed as a potential therapeutic strategy, its clinical efficacy remains controversial. This systematic review and meta-analysis evaluate the impact of antioxidants on endometriosis-related pain outcomes. METHODS: We conducted a systematic review and meta-analysis. A comprehensive search of PubMed, Scopus, Cochrane, Web of Science, and clinical trial registries (2000–January 2025) was conducted for randomized controlled trials (RCTs) investigating the effect of any oral antioxidant supplement, without dose or duration restrictions, in endometriosis patients and reporting quantitative data on at least one of the primary pain outcomes (dysmenorrhea, dyspareunia, or chronic pelvic pain). Primary outcomes included dysmenorrhea, dyspareunia, and chronic pelvic pain. Study risk of bias was assessed using the Cochrane RoB 2 tool, and evidence certainty was graded via the GRADE framework. Random-effects meta-analyses were performed to estimate pooled effects. RESULTS: Meta-analysis of available RCTs suggested a potential reduction in pain scores for dysmenorrhea (SMD = − 1.26, 95% CI: −2.19 to − 0.32) and chronic pelvic pain (SMD = − 1.07, 95% CI: −1.71 to − 0.42); however, extreme heterogeneity (I² > 90%) in these analyses indicates that these average effects are highly uncertain and should not be generalized specific clinical contexts. No significant effect was observed for dyspareunia. Subgroup analyses indicated that melatonin may be associated with the most consistent potential pain reduction. CONCLUSION: Current low- to very low-certainty evidence suggests that antioxidant supplementation, particularly melatonin, may be associated with improvements in dysmenorrhea and chronic pelvic pain in endometriosis. However, due to considerable inconsistency and methodological limitations across studies, these findings must be interpreted with caution. The results underscore the urgent need for high-quality, large-scale RCTs to confirm any potenti

BACKGROUND: Maintaining quality of life (QoL) for older cancer patients (≥ 70 years) undergoing systemic treatment is challenging. Melatonin supplementation could be a potential strategy. AIMS: The MEQAPAG trial investigated the effects of melatonin supplementation on this specific population's quality of life. METHODS: A multi-centre, double-blind, randomized placebo-controlled trial was implemented. Patients in the interventional arm received a daily dose of melatonin (2 mg/j for 90 days, 1-2 h before bedtime and after a meal) for the first three months of a new systemic treatment line. The primary endpoint was QoL assessment using the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) before and after supplementation. Among the secondary objectives, we evaluated the impact of supplementation on sleep and on urinary melatonin concentrations. We also studied safety and survival. RESULTS: One hundred and twenty-three patients were included in the study between July 2015 and January 2021. The trial was prematurely terminated due to futility. Only 61% (n = 59) of the patients were assessable and considered as compliant (i.e., at least two months of supplementation), 30 and 29 were allocated to the experimental and control groups respectively. Median age was 76 years (range [70, 88]). No difference in the QLQ-C30 questionnaire global score was shown. After the supplementation, the aMT6s concentration is 8,4 ng/mg creatinine (range [0.15, 201], IQI [0.99, 105]) in the experimental group. CONCLUSION: In an older cancer population, supplementation with 2 mg melatonin was safe but did not lead to any significant improvement in the global quality of life score on the QLQ-C30 for compliant patients. MEQAPAG trial provides novelty data on urinary aMT6s concentration for older cancer patients. TRIAL REGISTRATION NUMBER: NCT02454855, register on 05/12/2015. © 2025. The Author(s).

BACKGROUND: Poor sleep (defined by short sleep duration or poor quality) is a common condition with potential serious health consequences. Exogenous melatonin supplements have been found to effectively improve poor sleep but have also been shown to have heterogeneity of treatment effects (HTEs) between individuals. Personalized N-of-1 trials, in which each participant is the unit of analysis, are ideal for identifying whether a treatment with high HTE is beneficial for each individual patient. OBJECTIVE: This study aimed to identify the feasibility, acceptability, and effectiveness of a series of personalized N-of-1 trials of melatonin for poor sleep. METHODS: This study consisted of 60 digital, personalized N-of-1 crossover trials comparing the effects of 3.0 mg and 0.5 mg of melatonin versus placebo for poor sleep with randomization to 1 of 2 orders. The trial comprised a 2-week baseline period and a 12-week intervention period. The primary outcomes were usability of the personalized trial system (measured using the System Usability Scale [SUS]) and participant satisfaction with the trial. Effectiveness outcomes included sleep duration (measured using a Fitbit activity tracker [Google]) and sleep quality (measured using the consensus sleep diary). RESULTS: Participants rated the usability of the personalized trial as acceptable (average SUS score 76.3, SD 17.1), and 96% (55/57) of those who completed satisfaction surveys stated that they would recommend the trial to others. Importantly, indices of HTE were low for 3.0 mg and 0.5 mg doses of melatonin, indicating that the effect of these treatments on sleep duration and sleep quality did not substantially vary between participants and that averaged treatment responses are appropriate. Averaged participant sleep duration did not significantly differ between the 3.0 mg (P=.70) and 0.5 mg (P=.90) melatonin intervention periods and the baseline period. In addition, regression models did not show differences between different levels of melatonin and placebo periods for sleep duration or quality. CONCLUSIONS: Participant ratings of the usability of and satisfaction with this series of personalized N-of-1 trials of me

INTRODUCTION: Melatonin supplements and melatonin receptor agonists are linked to reduced delirium in the Intensive Care Unit (ICU) which we hypothesised may affect the length of stay (LOS) in ICU or in hospital. In this review, we identified and critically appraised the literature on the effect of exogenous melatonin and melatonin receptor agonists on the ICU and/or hospital LOS among adults admitted to the ICU. METHODS: Six electronic databases and three trial registries were searched for randomised controlled trials (RCTs). Screening, risk of bias assessment, quality appraisal, and level of evidence assessment were conducted and cross-checked by two reviewers independently. Meta-analyses with disease-specific subgroups were conducted to assess the mean difference in LOS for exogenous melatonin and melatonin receptor agonists compared with a placebo. RESULTS: Twenty RCTs were reviewed with 14 having a low risk of bias. For ICU LOS (18 studies) there was significant statistical heterogeneity (I2 = 73%); compared with placebo the 95% prediction interval for the mean difference was -3.18 and 1.39 days. For hospital stay (12 studies, I2 = 79%) the 95% prediction interval ranged from -6.68 to 3.52. Removing two statistical outliers, and correcting for publication bias, there was no overall statistically significant difference in mean ICU LOS (p-value = 0.298) or mean hospital LOS (p-value = 0.456). The subgroup analysis found statistically significant improvements for those who underwent coronary artery bypass graft surgery (ICU LOS -0.47 days, 95% CI: -0.78 to -0.16, p-value = 0.003); and patients with COVID-19 (hospital LOS -3.90 days, 95% CI: -6.28 to -1.51, p-value = 0.001). CONCLUSION: There was a very low certainty of evidence that melatonin and melatonin receptor agonists were associated with reductions in ICU and hospital LOS in ICU patients overall. However, further research is needed for surgical patients and those with pneumonia. Copyright: © 2025 Kelleher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided th

BACKGROUND: Oxidative stress (OS) accelerates the pathogenesis of coronary artery disease (CAD) by contributing to atherosclerotic plaque formation. Current research indicates that antioxidants can mitigate OS by reducing the production of free radicals. Despite many studies that have tested the effects of antioxidants on oxidative stress in patients with CAD, the literature still lacks an updated and comprehensive systematic review. The aim of this study was to identify the effects of administering exogenous antioxidants on OS levels among adult patients with CAD. METHODS: A systematic review searched PubMed, Medline, and CINAHL for randomized controlled trials (RCTs) published between January 2013 and May 2025, which examined antioxidants to lower OS in adult participants with CAD. Studies were excluded if participants had chronic or acute inflammatory conditions, renal failure, liver failure, or had undergone major operations before being enrolled. RESULTS: Among 2338 studies reviewed, 15 RCTs met the inclusion criteria. Out of the 15 RCTs, nine reported on supplemental antioxidants (i.e., L-carnitine and melatonin), and two reported on dietary antioxidants (Khorasan wheat diet and wine) that were effective at lowering OS (P < 0.05). One study found Brazil nuts (dietary antioxidants) ineffective at lowering OS. The three remaining RTCs reported that intravenously administered antioxidants, including alpha-lipoic acid, vitamin C, or N-acetylcysteine, significantly lowered OS. CONCLUSIONS: The reviewed RTCs provide evidence that antioxidants may lower OS in patients with CAD. The utility of this conclusion is limited by the studies' methodologies that examine various antioxidants and measure OS through a variety of biomarkers. This heterogeneity in methodologies between studies indicates that further research is needed with standardized interventions and outcomes.

This systematic review and network meta-analysis evaluated the efficacy of various therapies on sleep disturbances in children with autism spectrum disorder. We analyzed 35 randomized controlled trials comparing five interventions: melatonin, parent-mediated sleep education, behavioral interventions, physical activity, and adjunctive therapies. Standardized mean differences and surface under the cumulative ranking curve values were calculated to rank efficacy. Physical activity demonstrated the largest effect size (standardized mean difference = 1.13, surface under the cumulative ranking curve = 98.1%), followed by melatonin (standardized mean difference = 0.57, surface under the cumulative ranking curve = 62.8%) and behavioral interventions (standardized mean difference = 0.49, surface under the cumulative ranking curve = 51.6%). Parent education and adjunctive therapies showed limited efficacy. Heterogeneity (I² = 67%) was addressed via sensitivity analyses. A stepped-care model is recommended, prioritizing daytime physical activity (30-45 min, 3-5 sessions/week) combined with telehealth parent education as first-line treatment, followed by prolonged-release melatonin and therapist-supported cognitive behavioral therapy for non-responders.Lay abstractMany children with autism spectrum disorder struggle with sleep problems like trouble falling asleep, waking up at night, or not sleeping enough. This study looked at different treatments to improve sleep in these children, including melatonin supplements, parent-led bedtime routines, exercise programs, and other therapies. The researchers reviewed 35 studies involving over 2700 children with autism spectrum disorder. They compared how well each treatment worked using a method called network meta-analysis, which ranks treatments based on their effectiveness. Exercise programs, such as swimming or martial arts, were the most effective at improving sleep. These activities helped children fall asleep faster and stay asleep longer. Melatonin supplements also worked well but had side effects like morning drowsiness. Behavioral strategies, like structured bedtime routines, showed moderate benefits, while therapies like

BACKGROUND AND PURPOSE: Melatonin supplementation has shown potential benefits in the management of diabetes in clinical trials; however, prior meta-analyses have not specifically focused on individuals with type 2 diabetes mellitus (T2DM). This study investigates the efficacy of melatonin supplementation in improving glycemic control among patients with T2DM by systematically reviewing and analyzing data from randomized controlled trials (RCTs). METHODS: A comprehensive literature search was conducted in PubMed, Cochrane Library, Scopus, Web of Science, and Embase from their inception to September 2024. RCTs evaluating the effects of melatonin supplementation in adults diagnosed with T2DM were included. The methodological quality of the studies was assessed using the Cochrane Risk of Bias Tool. Data were synthesized and analyzed using RevMan version 5.3. RESULTS: A total of nine RCTs were included in the meta-analysis (n=9). These studies collectively involved 427 participants. Melatonin supplementation was associated with a statistically significant reduction in glycated hemoglobin (HbA1c) levels compared to placebo [mean difference [MD]: -0.65; 95% CI: -1.28, -0.02; P = 0.04], However, no significant effect was observed on fasting plasma glucose (FPG) levels [mean difference: -6.40; 95% CI: -15.79, 2.99; P = 0.18]. CONCLUSION: This meta-analysis suggests that melatonin supplementation significantly reduces HbA1c levels in patients with type 2 diabetes mellitus compared to placebo, indicating potential benefits for long-term glycemic control. However, no significant effect was observed on FPG levels. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024629557.

BACKGROUND: Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer's Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer's disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis. RESULTS: We identify 13 loci with cross-population associations including known loci at/near CR1, BIN1, TREM2, CD2AP, PTK2B, CLU, SHARPIN, MS4A6A, PICALM, ABCA7, APOE, and two novel loci not previously reported at 11p12 (LRRC4C) and 12q24.13 (LHX5-AS1). We additionally identify three population-specific loci with genome-wide significance at/near PTPRK and GRB14 in HIS and KIAA0825 in NHW. Pathway analysis implicates multiple amyloid regulation pathways and the classical complement pathway. Genes at/near our novel loci have known roles in neuronal development (LRRC4C, LHX5-AS1, and PTPRK) and insulin receptor activity regulation (GRB14). CONCLUSIONS: Using cross-population GWAS meta-analyses, we identify novel LOAD susceptibility loci in/near LRRC4C and LHX5-AS1, both with known roles in neuronal development, as well as several novel population-unique loci. Reflecting the power of diverse ancestry in GWAS, we detect the SHARPIN locus with only 13.7% of the sample size of the NHW GWAS study (n = 409,589) in which this locus was first observed. Continued expansion into larger multi-ancestry studies will provide even more power for further elucidating the genomics of late-onset Alzheimer's disease. © 2025. The Author(s).

BACKGROUND: Breast cancer has a high prevalence in women during the last years of their life. Exercise is instrumental during this recovery period. Nevertheless, little is known about the effects of combining nutritional supplements with physical activity. Therefore, this study aims to examine the impact of melatonin in conjunction with physical activity in breast cancer survivors (BCS). METHODS: Participants were postmenopausal women (60-75 years old) who had been diagnosed with stage I-III breast cancer 5 years ago and had received chemotherapy or radiotherapy. Participants were randomly assigned to two groups: experimental group (MEL) (n = 10), which received melatonin supplementation (6 mg/day), and the control group (CG) (n = 10), which received a placebo. Both groups followed an adapted physical activity program. After 10 weeks, body composition, physical condition, health-related quality of life and hormonal pattern were assessed in a randomized, single-blind, placebo-controlled trial (Clinical Trials.gov ID NCT06696378) following the Consolidated Standards of Reporting Trials. A Two-way repeated-measures analysis of variance (ANOVA) was used to examine the interaction effects (time × group) between MEL and CG. A significance level of p < 0.05 indicated a statistically significant difference. RESULTS: After 10 weeks, both groups showed a non-significant decrease (p > 0.05) in fat mass. Both MEL and CG exhibited a significant reduction (p < 0.05) in the Borg Rating of Perceived Exertion (RPE) when comparing the beginning (T1) and end (T2) of the study Additionally, statistically significant differences (p = 0.018) were observed overtime between T1 and T2 in the MEL and CG in RPE, with a moderate effect size (η 2 p = 0.347). On the other hand, the Quality-of-Life Questionnaire (four domains and total score) and Short Physical Performance Battery indicated no significant (p > 0.05) differences between MEL and CG. Finally, testosterone/cortisol ratio decreased in both groups at the end of intervention, but the difference was not statistically significant (p > 0.05). CONCLUSIONS: Melatonin supplementation (6 mg/day) for 10 weeks, combined with a physical activ