ABSTRACTSleep disturbances and mood changes are common during the climacteric, often linked to hormonal fluctuations caused by reduced ovarian function. Evidence suggests that long‐term melatonin administration may improve the quality of life in climacteric women. This study aimed to evaluate the effects of exogenous melatonin on climacteric symptoms, sleep quality, and reproductive hormones in women working fixed shifts. A randomized clinical trial was conducted with 46 nurses working fixed shifts at a hospital in São Paulo: morning (7:00–13:00, n = 16; intervention = 7, placebo = 9), afternoon (13:00–19:00, n = 15; intervention = 8, placebo = 7), and night (19:00–7:00, n = 15; intervention = 7, placebo = 8). Participants were randomly assigned to receive either 0.3 mg of melatonin or placebo. For night shift workers, melatonin was administered only on nights off, when they were sleeping at home; the same procedure was applied to morning and afternoon workers. Data collection included sociodemographic information, self‐reported sleep quality, and menopausal symptoms. Blood samples were collected at home to measure luteinizing hormone (LH), follicle‐stimulating hormone (FSH), estradiol, and progesterone before and after the intervention. A significant main effect of melatonin was observed, with a 15.8% reduction in climacteric symptoms compared with placebo (p = 0.01), independent of age or sleep duration, while no significant interaction with work shift was detected. Sleep quality improved by 35.33% on days off in the intervention group (p < 0.001), with morning shift workers showing a 32.46% improvement (p < 0.05). No significant changes were observed in reproductive hormone levels or total sleep duration. Exogenous melatonin effectively alleviates climacteric symptoms and improves sleep quality on days off, particularly among day‐shift workers, without affecting reproductive hormone concentrations or total sleep duration.Trial Registration: RBR‐10whktxm (UTN: U1111‐1305‐6221). Registered on 13 August 2025, retrospectively registered.

Introduction: Sleep and recovery are essential for optimizing exercise performance. However, the effectiveness of melatonin supplementation in improving sleep quality and next-day physical performance remains uncertain. Research has demonstrated the ergogenic effect of melatonin (N-acetyl-5-methoxytryptamine) (MEL) in increasing exhaustive aerobic activity. Associated with the effects of MEL, adult tissue stem cells (mesenchymal stem cells) mediate homeostasis and regeneration of tissues and organs, integrating signaling cues and metabolic inputs with the release of exosomes and microRNAs to enhance athletic performance. Objective: It was demonstrated through a systematic review study the regulation of melatonin and gut microbiota by cellular and molecular metabolic pathways, such as microRNAs and exosomes, in the process of muscle regeneration and increased sports performance. Methods: The PRISMA Platform systematic review rules were followed. The research was carried out from July to August 2025 in the Scopus, Embase, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 136 articles were found, and 55 articles were evaluated in full and 29 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 25 studies with a high risk of bias and 12 studies that did not meet GRADE and AMSTAR-2. Most studies showed homogeneity in their results, with X2=82.9%&gt;50%. It was concluded that administering 6 mg of melatonin at night improved performance during high-intensity exercise the following day and enhanced perceived recovery up to 72 hours after exercise. Melatonin intake during training has beneficial effects on physical performance and protects tissues against the deleterious effects of reactive oxygen species and cellular damage. Furthermore, nocturnal melatonin supplementation during an athlete's intense training session alleviated oxidative stress, leukocytosis, and cellular damage, and improved performance recovery. Melatonin plays important roles in regulating the regenerative activities of mesenchymal stem cells, which, along with nutrients, modulate the activities of exosomes and microRNAs in the muscle regeneration process.

This study evaluated the efficacy of a single 15 mg preoperative sublingual dose of melatonin in reducing anxiety as the primary outcome, and its effects on psychomotor performance, postoperative sleep quality, and early post-traumatic stress symptoms as secondary outcomes in patients undergoing mandibular third molar surgery. Forty-eight patients were randomly allocated to receive either melatonin (n=24) or an identical placebo (n=24) sublingually 45 minutes before surgery. Anxiety was assessed using the State-Trait Anxiety Inventory (STAI) and a Visual Analog Scale for Anxiety (VAS-A) at baseline, 45 minutes post-medication, and post-surgery. Intraoperative anxiety was measured with the surgeon-rated Interval Scale of Anxiety Response (ISAR). Psychomotor performance was evaluated with the Digit Symbol Substitution Test (DSST) at baseline and 45 minutes post-medication. Sleep quality was recorded via a patient diary for three postoperative nights, and post-traumatic stress symptoms were screened one week post-surgery using the Impact of Event Scale-Revised (IES-R). After adjusting for baseline scores using ANCOVA and GLM, no significant effect of melatonin was observed on state anxiety at any time point. Regarding secondary outcomes, no significant differences were observed in psychomotor performance, intraoperative anxiety from the surgeon's perspective (ISAR), postoperative sleep quality across the three nights, or early post-traumatic stress symptoms. The intervention was well tolerated, with no adverse events reported. A single 15 mg preoperative dose of sublingual melatonin did not demonstrate any significant benefit over placebo in reducing perioperative anxiety, improving psychomotor performance, enhancing postoperative sleep quality, or preventing early post-traumatic stress symptoms in patients undergoing mandibular third molar surgery.

Gestational nutrient restriction can reduce fetal growth efficiency, while melatonin supplementation can mitigate some of these negative outcomes. This study investigated placental fatty acid (FA) transporter gene expression and maternal-fetal FA concentrations in cattle supplemented with dietary melatonin during late gestational nutrient restrictions. Brangus heifers (n = 29) were fed a diet of 100% of National Research Council (NRC) requirements (ADQ) or 60% of NRC requirements (RES) from d 160 to d 240 of gestation. These groups were then randomly assigned to receive 20 mg of melatonin daily or no supplement, resulting in four treatment groups (ADQ-CON, n = 7; ADQ-MEL, n = 7; RES-CON, n = 7; RES-MEL, n = 8). On d 240, heifers underwent cesarean sections, in which amniotic fluid and blood samples from both the dam and fetus were collected to determine FA profiles. Placentomes were collected to determine transporter transcript abundance. Maternal concentrations of monounsaturated FA (P = 0.001) and total omega-3 (P = 0.041) were increased in RES versus ADQ-fed dams. Melatonin supplementation did not alter maternal FA profiles (P ≥ 0.081). Fetal concentrations of total omega-6 (n-6) were increased (P < 0.05) in RES-CON versus ADQ-CON, whereas ADQ-MEL and RES-MEL did not differ. Fetal concentrations of total branch chain fatty acids (BCFA) were increased (P < 0.05) in ADQ-MEL versus RES-MEL. Interestingly, maternal concentrations of C16:0, were increased (P = 0.015) in RES vs ADQ-fed dams, while the opposite was observed for amniotic fluid concentrations of C16:0 which were decreased (P = 0.003) in RES vs ADQ-fed dams. Amniotic fluid concentrations of total BCFA were decreased (P = 0.019) in RES versus ADQ-fed dams. Both caruncular and cotyledonary transcript abundance of CASR were decreased (P < 0.05) in RES-CON versus ADQ-CON, while melatonin supplementation rescued this depression in the cotyledon. Both caruncular and cotyledonary transcript abundance of SLC27A1 were increased (P < 0.05) in RES versus ADQ-fed dams. These results indicate that maternal melatonin supplementation differentially altered placental FA transporter transcript abundance and fetal FA profiles, demonstrating context-dependent effects under adequate versus restricted maternal nutrition.

To evaluate the efficacy of melatonin, a neurohormone regulating the sleep-wake cycle, in preventing delirium within 5 days of hospitalisation among older adult patients (≥65 years) admitted to general medical wards. Single-centre, double-blinded, randomised, placebo-controlled trial. General medical wards of a tertiary hospital in Oman. Patients aged ≥65 years admitted within 24 hours to general medical wards were screened. Key exclusion criteria included prevalent delirium, use of vasopressors, non-invasive ventilation, intensive or high-dependency unit admission and aphasia. Participants were randomly assigned to receive either 5 mg or 8 mg of melatonin or a placebo nightly for up to 5 days during hospitalisation or until discharge, whichever occurred first. The primary outcome was the incidence of delirium within 5 days, assessed using the 3-Minute Diagnostic Confusion Assessment Method. Secondary outcomes included delirium treatment, average sleep duration or sleep maintained, 28-day mortality and 28-day readmission. Analyses followed the intention-to-treat (ITT) principle, with per-protocol (PP) analyses conducted for robustness. The study was terminated early due to futility. At termination, a total of 115 participants were recruited, 109 of whom were included in the ITT analyses: 55 in the melatonin group (5 mg or 8 mg) and 54 in the placebo group. The overall incidence of delirium by day 5 was 2.75%, 3.64% in the melatonin group and 1.85% in the placebo group (p=1.000). No statistically significant differences were found in the average sleep duration (p=0.136), 28-day mortality (3.64% vs 1.85%, p=1.000) or 28-day readmission (21.82% vs 20.37%, p=0.853). PP analyses and subgroup sensitivity yielded similar findings. In this trial, melatonin did not significantly reduce the incidence of delirium. The lower-than-expected numbers of outcome events and resultant early termination for futility limited the study's power. As a result, the study findings should be interpreted with caution, and further research is necessary before definitive recommendations can be made. NCT06509191.

Effects of Melatonin Supplementation on Sleep Quality in Patients with Advanced Glaucoma: A Randomized, Double-Masked, Placebo-Controlled Crossover Trial.

This study aimed to evaluate the efficacy of a single preoperative 15mg sublingual dose of melatonin in reducing surgical discomfort, pain, edema, and trismus following mandibular third molar extraction. A randomized, double-blind, placebo-controlled trial was conducted with 46 patients allocated to receive melatonin (n = 22) or placebo (n = 24) 45min before surgery. The primary outcomes were intraoperative pain and discomfort and postoperative pain. Secondary outcomes included patient-perceived edema (VAS-Edema, days 1-5), trismus (5-point scale, days 1-5; interincisal measurement, day 7), and rescue medication consumption. No statistically significant differences were observed between the melatonin and placebo groups for any outcome. Intraoperative discomfort (QCirDental total score, p = 0.54) and pain (VAS, p = 0.67) were comparable. Similarly, postoperative pain levels across all time points (p = 0.67), edema over five days (p = 0.26), and trismus based on self-assessment (all days p > 0.50) and clinical measurement (p = 0.79) did not differ. Within the limitations of this clinical trial, a single 15mg preoperative dose of sublingual melatonin was not superior to placebo in alleviating surgical discomfort, pain, edema, or trismus after third molar extraction. Clinically, these findings suggest that melatonin may have limited effectiveness in managing common complications in oral surgery.

ObjectiveElectroencephalography (EEG) plays a fundamental role in the diagnosis and classification of epilepsy, and inducing sleep during EEG can improve patient cooperation and enhance the detection of epileptiform activity. Despite its importance, there is currently no standardized approach for sleep induction in pediatric EEG recordings. Consequently, practices such as melatonin administration and sleep deprivation are commonly utilized. This study aimed to compare the effectiveness of 5 mg melatonin versus partial sleep deprivation in inducing sleep during nap‐time EEGs in children with epilepsy.MethodsA randomized crossover trial was conducted involving 33 participants (mean age 14.5 years), each undergoing EEG following either melatonin administration or partial sleep deprivation. In the melatonin arm, participants received an oral dose 30 min before the recording, while in the sleep deprivation arm, sleep was restricted the previous night. The primary outcome was sleep onset latency, defined as the time from relaxation to non‐REM stage 2 sleep on EEG. Additionally, melatonin and its metabolite, 6‐hydroxy‐melatonin, were measured using liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS).ResultsThe study showed a mean sleep onset latency of 8.5 min after sleep deprivation and 10.1 min after melatonin administration, with a mean difference of 1.5 min. The analysis of covariance conducted with stratification based on sleep onset latency (five classes) and considering all patients confirmed that melatonin is non‐inferior to sleep deprivation in sleep onset latency, with 97.5% lower confidence limits of −0.37. Melatonin levels in the treated group confirmed adequate absorption, while they were undetectable in the sleep‐deprived group.SignificanceMelatonin is non‐inferior to partial sleep deprivation in reducing sleep onset latency, with comparable diagnostic yield and a favorable tolerability profile. The study demonstrates that 5 mg of melatonin is a safe, effective, and well‐tolerated alternative to partial sleep deprivation for sleep induction in pediatric EEG evaluations. Given its ease of use and consistent results, melatonin may be recommended as a practical standard for facilitating EEG recordings in children, particularly those with neurodevelopmental disorders.Plain Language SummaryThis randomized crossover trial evaluated the effectiveness and tolerability of melatonin administered before an EEG recording to induce sleep, compared with partial sleep deprivation. The results showed that melatonin helped children achieve sleep and was non‐inferior to sleep deprivation. Moreover, melatonin demonstrated a favorable tolerability profile, representing a safe and easier alternative to support sleep during EEG, particularly in children with neurodevelopmental disorders, and could enhance the efficiency and quality of pediatric EEG recordings.

Sleep bruxism has been investigated among sleep-related movement disorders, highly prevalent in children with Attention Deficit Hyperactivity Disorder (ADHD). Children and adolescents with ADHD tend to have more sleep disorders compared to those with neurotypical development. Although there are still no specific guidelines for the treatment of bruxism in this population, it is believed that exogenous melatonin may contribute to improving sleep quality and reducing bruxism episodes. Therefore, the present study aimed to report the case of a 13-year-old male adolescent diagnosed with ADHD and frequent episodes of sleep bruxism. The patient had a history of talking and agitation during sleep, in addition to daytime fatigue. He reported grinding his teeth at least three times a week, in addition to fatigue in the facial muscles and tooth sensitivity when consuming cold foods. To improve sleep quality, it was decided to administer 3 mg of melatonin for a period of 60 days, together with sleep hygiene recommendations. A significant improvement in sleep quality and a reduction in bruxism-related symptoms were observed. Although this is a single case, the findings suggest that melatonin may represent a promising therapeutic alternative, reinforcing the need for larger and more controlled clinical studies to investigate its efficacy and safety in this population

BackgroundPoor 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.ObjectiveThis study aimed to identify the feasibility, acceptability, and effectiveness of a series of personalized N-of-1 trials of melatonin for poor sleep.MethodsThis 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).ResultsParticipants 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.ConclusionsParticipant ratings of the usability of and satisfaction with this series of personalized N-of-1 trials of melatonin for sleep suggest these trials are both feasible and acceptable. However, our results show that melatonin supplements did not significantly improve sleep duration or sleep quality. Furthermore, the treatment effects’ lack of heterogeneity among participants suggests that future use of N-of-1 trials of melatonin for poor sleep is not needed.

This study aimed to examine the feasibility and effects of preoperative 5mg of melatonin and intraoperative 50mg of ketamine on postoperative delirium (POD) prevention in candidates for colorectal cancer surgery. In this randomized controlled trial, adults (> 18 years) who were candidates for elective colorectal cancer surgery were included in the study. Patients were randomized into four groups: placebo/saline (PS), melatonin/saline (MS), placebo/ketamine (PK), and melatonin/ketamine (MK). The groups received either 5 mg of oral melatonin or a placebo the night before surgery and 50 mg of ketamine or normal saline after anesthesia induction. The occurrence and severity of POD and pain severity were assessed via the confusion assessment method for the intensive care unit (CAM-ICU) and visual analogue scale (VAS), respectively (twice daily), until postoperative day 4. One-hundred and four patients (51% male, mean age: 56.29 ± 12.65) with a rate of 4.7 patients per week were recruited, with an attrition rate of 13.3%. The prevalence of POD was 17.3%, 22.23%, 16.67%, and 16.67% in the PS group, the MS group, the MK group, and the PK group, respectively. Compared with the control, none of the interventions significantly reduced the likelihood of POD occurrence. This randomized controlled trial demonstrated the feasibility of recruiting and retaining surgical patients for a multi-arm perioperative intervention study. Although the interventions did not significantly reduce the incidence of POD, the study design and procedures were feasible, with acceptable recruitment and attrition rates. Compared to placebo, none of the interventions significantly reduced the incidence of POD; however, time was a significant factor, with POD incidence, severity, and pain decreasing longitudinally. IR.TUMS.IKHC.REC.1401.374, registration date: 14 February 2023 and IRCT code: IRCT20120527009886N2, registration date: 07/03/2023.

Background: Stroke is one of the leading causes of annual mortality and disability for many individuals worldwide. Ischemic stroke has a high incidence and mortality rate, which significantly affects the quality of life and places an overwhelming mental and financial burden on the patients' families. Melatonin has a neuroprotective effect on patients with acute ischemic stroke. This study aimed to develop the employment of melatonin on clinical features of acute ischemic stroke. Methods: This double-blind, placebo-controlled clinical trial was conducted on 70 patients with acute ischemic stroke not eligible for reperfusion therapy who were admitted to Bu-Ali Hospital. The consent form was taken, and all of the patients received routine management. Participants were divided into two groups. The 35 patients received 10 mg of melatonin once daily for five days, and others received 10 mg of placebo. National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were recorded for all patients before treatment and after on days 5, 30, and 90. Results: The 70 patients included in this study were based on inclusion criteria. The severity of stroke and the functional status of patients were compared in both groups. The melatonin group showed a significant reduction in the NIHSS score from day five up to day thirty compared to the placebo group (P = 0.001). There was no difference in the mRS score between the two groups in this study (P &gt; 0.05). The relative frequency of the adverse event of sleepiness in patients receiving melatonin was significantly higher than in patients receiving placebo (P = 0.022). Conclusion: Patients who receive melatonin early after stroke have better improvement in post-stroke recovery and disabilities. These findings verify the results of other studies.

We studied the effect of melatonin in the original rectal suppositories on neurological status, microcirculation, and morphology of focal ischemic infarction in experimental acute cerebral ischemia modeled using the Chen technique (simultaneous diathermocoagulation of cerebral pial vessels in the posterior parts of the left frontal lobe and the anterior parts of the left parietal lobe). The animals of the experimental groups were administered either original rectal suppositories weighing 100 mg containing 2.5 mg of melatonin or a citicoline solution of 100 mg/kg intraperitoneally for 7 days. The neurological status was the Garcia and limb-placing test scores, microcirculation, and morphological parameters of the lesion on days 3 and 7. The use of original rectal suppositories reduced neurological deficits, increased the Garcia and limb-placing test scores, decreased the area of focal ischemic infarction, number of chromatolysis neurons, shadow cells, and an increase in the number of intact neurons and small vessels. The effects of original rectal suppositories with melatonin were significantly more pronounced than the effects of citicoline solution. The positive effect of melatonin in experimental acute cerebral ischemia was determined by its angiogenetic (formation of new blood vessels) and reparative (recovery of damaged neurons) effects.

BackgroundThis study aimed to assess the effect of oral melatonin consumption on improving heart function and reducing postoperative complications in patients undergoing coronary artery bypass grafting (CABG) surgery.MethodsA total of 60 CABG patients in the postoperative period were included in this randomized, double-blind, placebo-controlled trial. The patients were divided into three groups: Group 1 (n = 20, 5 mg melatonin), Group 2 (n = 20, 10 mg melatonin), and the placebo group (n = 20). The patients were discharged about 8 to 10 days after the surgery. Blood samples were taken from all the patients before and after the intervention (for 60 days), and Biochemical parameters including creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), total antioxidant capacity (TAC), nitric oxide (NO) assessed. Echocardiography and the measurement of systolic and diastolic blood pressure were also performed on participants.ResultsOur results showed that melatonin treatment significantly increased the ejection fraction (%EF) and TAC levels in both the treatment groups compared to the placebo group (P < 0.05). Moreover, the levels of inflammatory and oxidative biomarkers, including TNF-α, MDA, and NO, decreased in the intervention group significantly (P < 0.05). In the placebo group, %EF decreased significantly (P = 0.042), while MDA increased (P < 0.001) and TAC decreased (P = 0.002). No significant changes were observed in LDH and CK-MB levels. The comparison of serum biomarkers between the two treatment groups showed that 10 mg of melatonin was more effective than 5 mg, but the difference was not significant (P > 0.05).ConclusionThe present study showed that as a potential antioxidant, melatonin could alleviate oxidative stress and inflammation associated with CABG and is essential in improving overall heart function.Trial registration: IRCT20111119008129N14, first trial registration date: 01/08/2023.

With limited efficacy and safety of the methods to treat ischemic stroke (IS), melatonin (МТ) can be considered a promising neuroprotective agent having a pleiotropic mechanism of action. The study aimed to assess the effect of MT contained in original rectal suppositories on the neurological status and microcirculation in the injury focus in experimental acute cerebral ischemia (EACI) in vivo. A total of 30 sexually mature rats were divided into three groups, 10 animals per group: shamoperated (SO) animals; animals with EACI; animals with EACI receiving original rectal suppositories weighing 100 mg with 2.5 mg of melatonin (МТ) throughout 7 days. On days 3 and 7, neurological status was assessed using the Garcia JH score, Placing test, Bederson test; microcirculation rate (MR) was assessed in the brain injury focus by laser flowmetry. A significant decrease in the Garcia JH scores by 58.3% (p = 0.001), Placing Test scores by 57.9% (p = 0.002), along with the significant increase in the Bederson Test scores in animals with EACI compared to SO animals was reported on day 3; the significant decrease in the Garcia JH scores by 75% (p &lt; 0.001), Placing Test scores by 78.9% (p &lt; 0.001) and the significant increase in the Bederson Test scores were reported on day 7. MR decreased by 30% on day 3 (p = 0.02), by 38% on day 7 (p = 0.005). The use of the MT-based rectal suppositories resulted in the neurological deficit restoration in the form of the significant increase in the Gаrcia JH scores by 53.3% (p = 0.008), Placing Test scores by 50% (p = 0.016) and the significant decrease in the Bederson Test scores by 50% (p = 0.029) on day 3; on day 7, the significant increase in the Garcia JH scores by 233% (p &lt; 0.0001), Placing Test scores by 325% (p &lt; 0.0001) and the significant decrease in the Bederson Test scores by 100% (p &lt; 0.0001) were reported. MR increased by 12.5% on day 3 (p = 0.016), by 43.9% on day 7 (p = 0.005). The correlation analysis revealed the association between the neurological status and MR values: the neurological deficit improvement in animals with EACI in the context of receiving the MT-based rectal suppositories was associated with the MR increase in the ischemic focus in the brain. Thus, partial neurological status restoration in the context of using the MT-based rectal suppositories for EACI resulted from the MT vasoactive properties, which was reflected in the MR increase in the ischemic focus in the brain.

Sleep bruxism has been investigated among sleep-related movement disorders, highly prevalent in children with Attention Deficit Hyperactivity Disorder (ADHD). Children and adolescents with ADHD tend to have more sleep disorders compared to those with neurotypical development. Although there are still no specific guidelines for the treatment of bruxism in this population, it is believed that exogenous melatonin may contribute to improving sleep quality and reducing bruxism episodes. Therefore, the present study aimed to report the case of a 13-year-old male adolescent diagnosed with ADHD and frequent episodes of sleep bruxism. The patient had a history of talking and agitation during sleep, in addition to daytime fatigue. He reported grinding his teeth at least three times a week, in addition to fatigue in the facial muscles and tooth sensitivity when consuming cold foods. To improve sleep quality, it was decided to administer 3 mg of melatonin for a period of 60 days, together with sleep hygiene recommendations. A significant improvement in sleep quality and a reduction in bruxism-related symptoms were observed. Although this is a single case, the findings suggest that melatonin may represent a promising therapeutic alternative, reinforcing the need for larger and more controlled clinical studies to investigate its efficacy and safety in this population.

Background/Objectives: Sleep and recovery are critical for optimising exercise performance. However, the efficacy of melatonin supplementation in improving sleep quality and next-day physical performance remains unclear. This study examined the effects of melatonin ingestion on sleep and performance-related outcomes the following day in trained males. Methods: In a randomised, double-blind, placebo-controlled crossover study, 12 trained males (age: 21.92 ± 2.84 years) ingested 6 mg of melatonin (MEL) or a placebo (PLA) the night before performing the 5 m shuttle test (5mSRT). Before and after the 5mSRT, blood samples were collected. Peak heart rate (HRpeak) and rating of perceived exertion (RPE) were recorded throughout the test. Perceived recovery status (PRS) and delayed onset muscle soreness (DOMS) were measured before, 5 min, 24 h, 48 h, and 72 h after the test. The sleep/wake cycle was monitored during the night after ingestion. Results: Data were analysed using paired t-tests, Wilcoxon tests, and two-way ANOVAs, with significance set at p < 0.05. Compared to PLA, MEL did not modify any sleep parameters or blood markers (all p > 0.05). However, MEL improved total distance, fatigue index, the percentage decrement between sprints, and HRpeak (all p < 0.05) in the 5mSRT compared to PLA. MEL also enhanced PRS values up to 72 h post-exercise and reduced DOMS (all p < 0.05). Conclusion: In summary, 6 mg of melatonin taken at night enhanced next-day high-intensity exercise performance and improved perceived recovery up to 72 h post-exercise.

This pilot study evaluated the therapeutic effects of oral melatonin in patients diagnosed with primary Sj&amp;ouml;gren&amp;rsquo;s syndrome (pSS) and dry eye disease (DED). Twelve patients were treated with 5 mg of melatonin daily over an eight-week period. After treatment, significant improvements were recorded in Schirmer I test, tear break-up time (TBUT), and National Eye Institute (NEI) staining scores. Symptom severity decreased according to the Ocular Surface Disease Index (OSDI) and the EULAR Sj&amp;ouml;gren&amp;rsquo;s Syndrome Patient Reported Index (ESSPRI). Additionally, a significant reduction in serum interleukin-6 (IL-6) levels was observed, while C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) remained unchanged. Visual inspection of individual scores demonstrated a consistent trend of clinical improvement. No adverse effects were reported during the study period. These preliminary findings suggest that melatonin supplementation could represent a safe, adjunctive therapeutic strategy for managing autoimmune dry eye in pSS patients. Further large-scale clinical trials are warranted to confirm these results and explore the underlying mechanisms.

Abstract Introduction Melatonin supplements are widely used in the United States to manage sleep disorders. However, concerns have been raised regarding the accuracy of labeled dosages and the presence of impurities in these over-the-counter products. In the U.S., melatonin is regulated as a dietary supplement, which means it is not subject to the stringent quality control standards applied to pharmaceutical products. This regulatory gap can lead to significant variability in product quality, potentially impacting consumer safety and therapeutic efficacy. Methods We evaluated ten commercially available melatonin supplements in the U.S. Each sample was prepared by dissolving a quantity equivalent to approximately 6 mg of melatonin in 10 mL of water, followed by sonication to ensure complete dissolution. Subsequently, 300 mL of a methanol/water mixture (7:3) was added, and the solution was sonicated for 20 minutes and vigorously shaken for an additional 20 minutes. The final volume was adjusted to 500 mL with the methanol/water mixture, filtered through a 0.45-micron membrane, discarding the initial 4 mL, and the filtrate was analyzed. Quantitative analysis and impurity profiling were conducted using high-performance liquid chromatography (HPLC) methods adapted from our quality assurance standards. Results Among the ten products analyzed, four exhibited melatonin content deviating beyond the acceptable range of 90–110% of the labeled amount, indicating substantial discrepancies. Impurity testing revealed that, while all products met the specific impurity thresholds for known related substances (e.g., 5-methoxytryptamine ≤0.5%), several products contained higher overall levels of unidentified impurities, with some approaching 1% of the total content. Conclusion The findings highlight significant quality control issues in commercially available melatonin supplements in the U.S., with 40% of products failing to meet acceptable content standards and several exhibiting elevated impurity levels. These inconsistencies may compromise therapeutic efficacy and pose safety risks to consumers. There is an urgent need for enhanced regulatory oversight and stringent quality assurance protocols in the manufacturing of melatonin supplements to ensure product consistency, efficacy, and consumer safety. Healthcare providers should be aware of these quality variations when recommending melatonin and consider advocating for products that have undergone rigorous third-party testing. Support (if any)

Background &amp; objectives: Several studies have shown that melatonin and vitamin C used as an analgesic adjuvant, can spare opioid use, resulting in a better analgesic profile with fewer adverse effects and shorter hospital stay. However, we found no studies which might have investigated the impact of a combination of both. We compared the effect of melatonin, vitamin C, and their combination on postoperative opioid consumption. Methodology: Sixty patients scheduled for major abdominal surgeries were randomly allocated into three equal groups with 20 patients in each; melatonin group (Group M), vitamin C (Group C), and combined melatonin and vitamin C (Group CM). Two hours before surgery, all patients received the study medications orally, which was continued for 3 days postoperative at the same time of the first administration; Group M received 10 mg of melatonin, Group C received 1 gm of vitamin C, and Group MV received both melatonin (10 mg) and vitamin C (1 gm). The primary outcome was the total morphine consumption in 24 hours postoperatively, with patients, pain scores as measured by Numeric Pain Rating Scale (NPRS), the incidence of postoperative nausea and vomiting (PONV), and postoperative chronic pain as secondary outcomes. Results: Postoperative morphine consumption (in the first 24 hours) was significantly lower in Group CM (16.7 ± 2.4 mg) than in Group M (20.98 ± 1.38 mg), and Group C (24.36 ± 3.12 mg) (P &lt; 0.001). Group CM showed lower pain scores, decreased incidence of PONV, and a longer time to first request for analgesics. However, lower sedation scores were observed. There was no statistical difference among all groups regarding post-operative chronic pain incidence. Conclusion: Combined use of melatonin and vitamin C in patients undergoing major abdominal surgery with mid-line incision provides a synergistic analgesic effect for the postoperative pain management with lower postoperative pain scores, less opioid consumption, and lower incidence of PONV compared to the use of any one of these. Abbreviations: CPSP: Chronic Post-Surgical Pain, NPRS: Numeric Pain Rating Scale, PONV: postoperative nausea and vomiting, TAHBSO: Total Abdominal Hysterectomy with Bilateral Salpingo-Oophorectomy Keywords: Melatonin; major abdominal surgery; Numeric Pain Rating Scale; opioid consumption; postoperative pain; PONV; vitamin C. Citation: Abdelhakim AK, Shaker DSM, Hamimy WI, Attalla MA, Radwan KG, Abdelhady AKM. Anaesth. pain intensive care 2025;29(3):556-664. DOI: 10.35975/apic.v29i3.2790 Received: January 03, 2025; Revised: March 12, 2025; Accepted: March 22, 2025