멜라토닌 (0.5mg)
Melatonin (0.5mg)
📚 관련 논문 (20편)
1. Eur J Obstet Gynecol Reprod Biol. 2014 Mar;174:80-5. doi: 10.1016/j.ejogrb.2013.11.027. Epub 2013 Dec 9. The effect of estradiol, progesterone, and melatonin on estrous cycling and ovarian aromatase expression in intact female mice. Bondi CD(1), Alonso-Gonzalez C(2), Clafshenkel WP(1), Kotlar
2. Epilepsy Behav. 2011 Oct;22(2):200-6. doi: 10.1016/j.yebeh.2011.07.002. Epub 2011 Aug 15. The interaction of melatonin and agmatine on pentylenetetrazole-induced seizure threshold in mice. Moezi L(1), Shafaroodi H, Hojati A, Dehpour AR. Author information: (1)Department of Pharmacology, Scho
3. Biomed Pharmacother. 2011 Jun;65(3):215-9. doi: 10.1016/j.biopha.2011.02.008. Epub 2011 May 5. Protective effects of tryptophan on neuro-inflammation in rats after administering lipopolysaccharide. Del Angel-Meza AR(1), Dávalos-Marín AJ, Ontiveros-Martinez LL, Ortiz GG, Beas-Zarate C, Chapar
4. Cochrane Database Syst Rev. 2002;(2):CD001520. doi: 10.1002/14651858.CD001520. Melatonin for the prevention and treatment of jet lag. Herxheimer A(1), Petrie KJ. Author information: (1)UK Cochrane Centre, 9 Park Crescent, London N3 2NL, UK. andrew herxheimer@compuserve.com Update of Coch
5. Cochrane Database Syst Rev. 2001;2002(1):CD001520. doi: 10.1002/14651858.CD001520. Melatonin for preventing and treating jet lag. Herxheimer A(1), Petrie KJ. Author information: (1)UK Cochrane Centre, 9 Park Crescent, London N3 2NL, UK. andrew herxheimer@compuserve.com Update in Cochran
1. Nutrients. 2026 Apr 9;18(8):1182. doi: 10.3390/nu18081182. Non-Mineral Antioxidant Supplementation in Endometriosis: Biological Rationale, Clinical Evidence, and Therapeutic Implications-A Narrative Review. Pokorska-Niewiada K(1), Janda-Milczarek K(2), Kayumov K(3), Ziętek M(4), Szczuko M(5). Author information: (1)Department of Toxicology, Dairy Technology and Food Storage, West Pomeranian University of Technology in Szczecin, 71-454 Szczecin, Poland. (2)Department of Biology, Parasitology and Pharmaceutical Botany, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland. (3)Department of Human and Animals Physiology, National University of Uzbekistan named after Mirzo Ulugbek, Tashkent 100174, Uzbekistan. (4)Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland. (5)Department of Bromatology and Diagnostic Nutrition, Pomeranian Medical University, 70-111 Szczecin, Poland. 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. DOI: 10.3390/nu18081182 PMID: 42074994 [Indexed for MEDLINE]
2. J Pineal Res. 2026 Mar;78(2):e70130. doi: 10.1111/jpi.70130. Melatonin Supplementation in Adult Patients With Atopic Dermatitis: A Randomized Clinical Trial. Heidari Z(1), Gharibi G(2), Alaeen H(3)(4), Ghadrdan E(2), Shahrestanaki E(5), Sadeghi-Ghadi Z(6)(7), Sahebkar A(8)(9)(10), Daei M(2). Author information: (1)Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. (2)Department of Clinical Pharmacy, School of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran. (3)Department of Dermatology, Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran. (4)Department of Dermatology, Alborz University of Medical Sciences, Karaj, Iran. (5)Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran. (6)Department of Pharmaceutics, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. (7)Institute of Herbal Medicines and Metabolic Disorders, Mazandaran University of Medical Sciences, Sari, Iran. (8)Applied Biomedical Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran. (9)Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, India. (10)Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. 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. DOI: 10.1111/jpi.70130 PMID: 41787942 [Indexed for MEDLINE]
3. Brain Behav. 2026 Jan;16(1):e71193. doi: 10.1002/brb3.71193. Adaptogenic Effects of Mushroom Blend Supplementation on Stress, Fatigue, and Sleep: A Randomised, Double-Blind, and Placebo-Controlled Trial. Hisamuddin AS(1), Ramli F(1), Leo TK(1), Zain MSC(1)(2), Wong MS(3)(4), Suhaili MR(3), Lee LJ(5), Lee TY(6). Author information: (1)Research and Development Department, Nexus Wise Sdn Bhd, Petaling Jaya, Malaysia. (2)Bioresource Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Penang, Malaysia. (3)Faculty of Medicine, Nursing and Health Sciences, SEGi University, Petaling Jaya, Selangor, Malaysia. (4)Department of Medical Education, Sif Jeffrey Cheah Sunway Medical School, Faculty of Medical and Life Sciences, Sunway University, Malaysia. (5)Prima Nexus Sdn. Bhd., Bandar Puteri Puchong, Selangor, Malaysia. (6)Clinical Laboratory Science Section, Institute of Medical Science Technology, Universiti Kuala Lumpur, Kajang, Selangor, Malaysia. 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. DOI: 10.1002/brb3.71193 PMCID: PMC12808922 PMID: 41540766 [Indexed for MEDLINE]
4. Nutrients. 2025 Dec 31;18(1):134. doi: 10.3390/nu18010134. Comprehensive Effects of Melatonin Supplementation on Cardiometabolic Risk Factors: A Systematic Review and Dose-Response Meta-Analysis. Mohammadi S(1), Ashtary-Larky D(2), Erfanian-Salim M(3), Alaghemand N(2), Yousefi M(4), Sanjari Pirayvatlou P(5), Mirkarimi M(6), Mavi SA(7), Alavi I(8), Ettehad Y(5), Mehrbod M(9), Asbaghi O(10), Suzuki K(11), Reiter RJ(12). Author information: (1)Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. (2)Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 6135715794, Iran. (3)Department of Pediatric Cardiology, Children's Medical Center, Tehran University of Medical Sciences, Tehran 1416753955, Iran. (4)Department of Cardiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 6135715794, Iran. (5)Department of Internal Medicine, Faculty of Medicine, Alborz University of Medical Sciences, Karaj 3149969415, Iran. (6)Department of Pediatrics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 6135715794, Iran. (7)Department of Community Medicine, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 6135715794, Iran. (8)Division of Cardiovascular Medicine, School of Medicine, University of Louisville, Louisville, KY 40222, USA. (9)Department of Internal Medicine, Mercy San Juan Medical Center, Carmichael, CA 95608, USA. (10)Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran. (11)Faculty of Sport Sciences, Waseda University, Tokorozawa 359-1192, Japan. (12)Department of Cell Systems and Anatomy, Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229, USA. 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. DOI: 10.3390/nu18010134 PMCID: PMC12787795 PMID: 41515249 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.
5. Nutrients. 2025 Dec 19;18(1):14. doi: 10.3390/nu18010014. Heat-Treated Limosilactobacillus fermentum PS150 Improves Sleep Quality with Severity-Dependent Benefits: A Randomized, Placebo-Controlled Trial. Lee MC(1)(2), Chen CY(1)(3), Chen CY(1), Huang CC(1). Author information: (1)Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan City 333325, Taiwan. (2)Center for General Education, Taipei Medical University, Taipei 110301, Taiwan. (3)Physical Education Office, National Taipei University of Business, Taipei 100025, Taiwan. 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 evident among participants with greater baseline symptom burden, suggesting potential utility in more symptomatic populations. DOI: 10.3390/nu18010014 PMCID: PMC12787598 PMID: 41515133 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
6. Food Sci Nutr. 2026 Jan 2;14(1):e71285. doi: 10.1002/fsn3.71285. eCollection 2026 Jan. A Randomized, Triple-Blind, Placebo-Controlled, Parallel Clinical Trial Investigating Safety and Efficacy of Corn Leaf Extract on Sleep Quality in a Healthy Population With Difficulty Falling or Staying Asleep. Doma KM(1), Zamzam A(1), Crowley DC(1), Guthrie N(1), Lewis ED(1). Author information: (1)KGK Science Inc. London Ontario Canada. 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. DOI: 10.1002/fsn3.71285 PMCID: PMC12759108 PMID: 41488152 Conflict of interest statement: The authors declare no conflicts of interest.
7. Reprod Biol Endocrinol. 2025 Dec 30;23(1):164. doi: 10.1186/s12958-025-01485-x. Efficacy of antioxidant supplementation in alleviating endometriosis-related pain: insights from a systematic review and meta-analysis of RCTs. Esmaeilzadeh S(#)(1), Sadrzadeh A(#)(2), Moher D(3), Sepidarkish M(1), Alamolhoda SH(4), Mirabi P(5). Author information: (1)Infertility and Reproductive Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. (2)Student Research Committee, Babol University of Medical Sciences, Babol, Iran. (3)School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada. (4)Midwifery and Reproductive Health Research Center, Department of Midwifery and Reproductive Health, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (5)Infertility and Reproductive Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. parvaneh_mirabi@yahoo.com. (#)Contributed equally 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 potential benefits and define the clinical role of antioxidants in endometriosis management. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12958-025-01485-x. DOI: 10.1186/s12958-025-01485-x PMCID: PMC12751427 PMID: 41462252 Conflict of interest statement: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests.
8. BMC Geriatr. 2025 Dec 20;26(1):105. doi: 10.1186/s12877-025-06899-1. Melatonin supplementation for quality of life in older patients with advanced cancer: a randomized controlled trial. Ginzac A(1)(2)(3), Bourbouloux E(4), Rivoirard R(5), Jouannaud C(6), Hager MO(7), Dubois S(8), Kwiatkowski F(9), Molnar I(10)(11)(9), Thivat E(10)(11)(9), Durando X(10)(11)(9)(8). Author information: (1)INSERM U1240 Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne, Clermont-Ferrand, France. angeline.ginzac@clermont.unicancer.fr. (2)Centre d'Investigation Clinique, UMR501, Clermont-Ferrand, France. angeline.ginzac@clermont.unicancer.fr. (3)Division de Recherche Clinique, Délégation Recherche Clinique et Innovation, Centre Jean PERRIN, Clermont-Ferrand, France. angeline.ginzac@clermont.unicancer.fr. (4)Institut de Cancérologie de l'Ouest Centre René GAUDUCHEAU, service d'oncologie médicale, Nantes, France. (5)Institut de cancérologie Lucien-Neuwirth, service d'oncologie médicale, Saint-Priest-en-Jarez, France. (6)Institut Jean GODINOT, service d'oncologie médicale, Reims, France. (7)Centre Jean PERRIN, service soins oncologiques de support, Clermont-Ferrand, France. (8)Centre Jean PERRIN, service d'oncologie médicale, Clermont-Ferrand, France. (9)Division de Recherche Clinique, Délégation Recherche Clinique et Innovation, Centre Jean PERRIN, Clermont-Ferrand, France. (10)INSERM U1240 Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne, Clermont-Ferrand, France. (11)Centre d'Investigation Clinique, UMR501, Clermont-Ferrand, France. 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). DOI: 10.1186/s12877-025-06899-1 PMCID: PMC12836914 PMID: 41421991 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Ethics approval and consent to participate: The study protocol was approved by the Sud-Est VI ethics committee (France) and by the French National Agency for the Safety of Medicines and Health Products (N° EudraCT: 2014-003505-14). All questionnaires, including the MMSE, were used with appropriate permissions following post hoc rectification with PAR. Competing interests: The authors declare no competing interests. Research involving human participants: All the procedures performed in the study, involving human participants, were in accordance with the ethical standards of the institutional and/or the national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethics standards. Informed consent: Written informed consent was obtained from all the participants included in the study.
9. JMIR Form Res. 2025 Sep 26;9:e58192. doi: 10.2196/58192. A Series of Personalized Melatonin Supplement Interventions for Poor Sleep: Feasibility Randomized Crossover Trial for Personalized N-of-1 Treatment. Butler MJ(1)(2), Chandereng T(1)(2), Ahn H(1)(2), Slotnick S(1)(2), Miller D(1)(2), Perrin A(1)(2), Rodillas J(1)(2), Friel CP(1)(2), Goodwin AM(1)(2), Cheung YK(3), Davidson KW(1)(2). Author information: (1)Northwell, 2000 Marcus Ave, Suite 300, New Hyde Park, NY, 11042-1069, United States, 1 6467667181. (2)Institute of Health System Science, Feinstein Institutes For Medical Research, Manhasset, NY, United States. (3)Mailman School of Public Health, Columbia University, New York, NY, United States. 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 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. © Mark J Butler, Thevaa Chandereng, Heejoon Ahn, Stefani Slotnick, Danielle Miller, Alexandra Perrin, Jordyn Rodillas, Ciaran P Friel, Ashley M Goodwin, Ying Kuen Cheung, Karina W Davidson. Originally published in JMIR Formative Research (https://formative.jmir.org). DOI: 10.2196/58192 PMCID: PMC12468169 PMID: 41004640 [Indexed for MEDLINE] Conflict of interest statement: Conflicts of Interest: None declared.
10. PLoS One. 2025 Sep 8;20(9):e0332031. doi: 10.1371/journal.pone.0332031. eCollection 2025. The effect of exogenous melatonin and melatonin receptor agonists on intensive care unit and hospital length of stay: A systematic review and meta-analysis. Kelleher AB(1), O'Donovan M(2), O'Doherty D(1)(3), Lavery R(1)(4), Lehane E(1), Saab MM(1). Author information: (1)Catherine McAuley School of Nursing and Midwifery, University College Cork, Cork, Ireland. (2)College of Medicine and Health, University College Cork, Cork, Ireland. (3)Oncology Department, Beaumont Hospital, Dublin, Ireland. (4)Mater Private Hospital, City Gate, Mahon, Cork, Ireland. 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 the original author and source are credited. DOI: 10.1371/journal.pone.0332031 PMCID: PMC12416736 PMID: 40920753 [Indexed for MEDLINE] Conflict of interest statement: The authors have declared that no competing interests exist.
11. Clin Nutr ESPEN. 2025 Oct;69:794-801. doi: 10.1016/j.clnesp.2025.08.037. Epub 2025 Sep 4. Effects of antioxidants on oxidative stress in adult patients with coronary artery disease: A systematic review. Alhusban IM(1), Chung ML(2), Biddle M(3). Author information: (1)College of Nursing, University of Kentucky, 751 Rose Street Lexington, KY 40536, USA. Electronic address: imal230@uky.edu. (2)School of Nursing, Vanderbilt University, 2201 West End Ave, Nashville, TN 37235, USA. (3)College of Nursing, University of Kentucky, 751 Rose Street Lexington, KY 40536, USA. 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. Copyright © 2025 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved. DOI: 10.1016/j.clnesp.2025.08.037 PMID: 40914496 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare no conflict of interest.
12. Autism. 2026 Jan;30(1):9-19. doi: 10.1177/13623613251362273. Epub 2025 Aug 12. Pharmacological or non-pharmacological therapies? The impact of different therapies on sleep in children with autism spectrum disorder: A systematic review and network meta-analysis. Sirao L(1), Yaping H(1), Yunshan L(1), Dan L(1). Author information: (1)Hunan Normal University, China. 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 weighted blankets or iron supplements had little impact. This study helps families and doctors choose the best treatments for sleep problems in children with autism spectrum disorder. Exercise is a safe, low-cost option that not only improves sleep but also enhances daytime behavior. The findings support starting with physical activity and parent coaching before trying medications like melatonin. Recognizing effective treatments can reduce stress for caregivers and improve quality of life for children with autism spectrum disorder. DOI: 10.1177/13623613251362273 PMID: 40792489 [Indexed for MEDLINE] Conflict of interest statement: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
13. Front Endocrinol (Lausanne). 2025 Jul 8;16:1572613. doi: 10.3389/fendo.2025.1572613. eCollection 2025. The effect of melatonin supplementation on glycemic control in patients with type 2 diabetes. Lv X(#)(1), Sun H(#)(1), Ai S(2), Zhang D(2), Lu H(2). Author information: (1)Master Degree Candidate, First School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. (2)Department of Anesthesiology, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, China. (#)Contributed equally 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. Copyright © 2025 Lv, Sun, Ai, Zhang and Lu. DOI: 10.3389/fendo.2025.1572613 PMCID: PMC12279524 PMID: 40698248 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
14. Genome Biol. 2025 Jul 17;26(1):210. doi: 10.1186/s13059-025-03564-z. Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease. Rajabli F(#)(1)(2), Benchek P(#)(3), Tosto G(#)(4)(5), Kushch N(2), Sha J(6), Bazemore K(6), Zhu C(7), Lee WP(8), Haut J(6), Hamilton-Nelson KL(2), Wheeler NR(3)(9), Zhao Y(8), Farrell JJ(7), Grunin MA(3), Leung YY(8), Kuksa PP(8), Li D(7), da Fonseca EL(2), Mez JB(10), Palmer EL(3), Pillai J(11), Sherva RM(7), Song YE(3)(9), Zhang X(7)(12), Ikeuchi T(13), Iqbal T(6), Pathak O(8), Valladares O(8), Reyes-Dumeyer D(4)(5), Kuzma AB(8), Abner E(14), Adams LD(1), Adams PM(15), Aguirre A(16), Albert MS(17), Albin RL(18)(19)(20), Allen M(21), Alvarez L(22), Apostolova LG(23)(24), Arnold SE(25), Asthana S(26)(27)(28), Atwood CS(26)(27)(28), Auerbach S(10), Ayres G(16), Baldwin CT(7), Barber RC(22), Barnes LL(29)(30)(31), Barral S(4)(5)(32), Beach TG(33), Becker JT(34), Beecham GW(2), Beekly D(35), Benitez BA(36), Bennett D(29)(31), Bertelson J(37), Bird TD(38)(39), Blacker D(40)(41), Boeve BF(42), Bowen JD(43), Boxer A(44), Brewer J(45), Burke JR(46), Burns JM(47), Buxbaum JD(48)(49)(50), Cairns NJ(51), Cantwell LB(8), Cao C(52), Carlson CS(53), Carlsson CM(27)(28), Carney RM(54), Carrasquillo MM(21), Chasse S(55), Chesselet MF(56), Chin NA(26)(27), Chui HC(57), Chung J(7), Craft S(58), Crane PK(59), Cribbs DH(60), Crocco EA(61), Cruchaga C(62)(63), Cuccaro ML(1)(2), Cullum M(15), Darby E(64), Davis B(65), De Jager PL(66), DeCarli C(67), DeToledo J(68), Dick M(69), Dickson DW(21), Dombroski BA(8), Doody RS(64), Duara R(70), Ertekin-Taner N(21)(71), Evans DA(72), Faber KM(73), Fairchild TJ(74), Fallon KB(75), Fardo DW(76), Farlow MR(77), Fernandez-Hernandez V(36), Ferris S(78), Friedland RP(79), Foroud TM(73), Frosch MP(80), Fulton-Howard B(81), Galasko DR(45), Gamboa A(82)(83), Gearing M(84)(85), Geschwind DH(56), Ghetti B(86), Gilbert JR(1)(2), Go RCP(75), Goate AM(48), Grabowski TJ(39)(87), Graff-Radford NR(21)(71), Green RC(88), Growdon JH(89), Hakonarson H(90)(91), Hall J(22), Hamilton RL(92), Harari O(63), Hardy J(93)(94), Harrell LE(95), Head E(96), Henderson VW(97)(98), Hernandez M(68), Hohman T(99)(100), Honig LS(4), Huebinger RM(101), Huentelman MJ(102), Hulette CM(103), Hyman BT(89), Hynan LS(15)(104)(105), Ibanez L(106)(107), Jarvik GP(108)(109), Jayadev S(39), Jin LW(110), Johnson K(68), Johnson L(82), Kamboh MI(111)(112)(113), Karydas AM(44), Katz MJ(114), Kauwe JS(115)(116), Kaye JA(117)(118), Keene CD(119), Khaleeq A(64), Kikuchi M(13), Kim R(96), Knebl J(82), Kowall NW(10)(120), Kramer JH(121), Kukull WA(122), LaFerla FM(123), Lah JJ(124), Larson EB(125), Lerner A(3), Leverenz JB(11), Levey AI(124), Lieberman AP(126), Lipton RB(114), Logue M(7)(127)(128), Lopez OL(34), Lunetta KL(12), Lyketsos CG(129), Mains D(82)(83), Margaret FE(130)(131), Marson DC(95), Martin ER(1)(2), Martiniuk F(132), Mash DC(133), Masliah E(45)(134), Massman P(64), Masurkar A(78), McCormick WC(59), McCurry SM(135), McDavid AN(53), McDonough S(136), McKee AC(10)(137), Mesulam M(130)(131), Miller BL(138), Miller CA(139), Miller JW(110), Montine TJ(140), Monuki ES(141), Morris JC(51)(107)(142)(143), Mukherjee S(59), Myers AJ(61), Nguyen T(104), Obisesan T(144), O'Bryant S(145), Olichney JM(146), Ory M(147), Palmer R(148), Parisi JE(149), Paulson HL(18)(20), Pavlik V(64), Paydarfar D(16), Perez V(68), Peskind E(150), Petersen RC(42), Petrovitch H(151), Pierce A(60), Polk M(148), Poon WW(69), Potter H(152), Qu L(8), Quiceno M(153)(154), Quinn JF(117)(118), Raj A(52), Raskind M(150), Reiman EM(102)(155)(156)(157), Reisberg B(78)(158), Reisch JS(65), Ringman JM(159), Roberson ED(95), Rodriguear M(64), Rogaeva E(160), Rosen HJ(44), Rosenberg RN(104), Royall DR(161), Sabbagh M(162), Sadovnick AD(163), Sager MA(27), Sano M(50), Saykin AJ(73)(164), Schneider JA(29)(31)(165), Schneider LS(57)(166), Seeley WW(44), Slifer SH(2), Small S(4)(5), Smith AG(52), Smith JP(65), Sonnen JA(119), Spina S(86), George-Hyslop PS(167)(168), Starks TD(169)(170), Stern RA(10), Stevens AB(171)(172)(173), Strittmatter SM(174), Sultzer D(175), Swerdlow RH(47), Tanzi RE(89), Tilson JL(176), Trojanowski JQ(8), Troncoso JC(177), Tsolaki M(178), Tsuang DW(38)(150), Van Deerlin VM(8), van Eldik LJ(179), Vance JM(1)(2), Vardarajan BN(4), Vassar R(130)(131), Vinters HV(159)(180), Vonsattel JP(4), Weintraub S(181), Welsh-Bohmer KA(46)(182), Whitehead PL(2), Wijsman EM(108)(109)(183), Wilhelmsen KC(55), Williams B(184), Williamson J(4), Wilms H(68), Wingo TS(124), Wisniewski T(185)(186), Woltjer RL(184), Woon M(37), Wright CB(187), Wu CK(68), Younkin SG(21)(71), Yu CE(59), Yu L(28)(29)(31), Zhu X(188), Kunkle BW(1)(2), Bush WS(3)(9), Miyashita A(13), Byrd GS(189), Wang LS(8), Farrer LA(10)(7)(12)(189)(190), Haines JL(3)(9), Mayeux R(4), Pericak-Vance MA(1)(2), Schellenberg GD(8), Jun GR(#)(7)(12)(189), Reitz C(#)(5)(32)(191), Naj AC(#)(192)(193); Alzheimer’s Disease Genetics Consortium (ADGC). Author information: (1)Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA. (2)The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA. (3)Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA. (4)Taub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center Department of Neurology, Columbia University, New York, NY, USA. (5)Department of Neurology, Columbia University, New York, NY, USA. (6)Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. (7)Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. (8)Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. (9)Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA. (10)Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. (11)Cleveland Clinic Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, OH, USA. (12)Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. (13)Molecular Genetics Division, Brain Research Institute, Niigata University, Niigata, Japan. (14)Sanders-Brown Center on Aging, Department of Epidemiology, College of Public Health, University of Kentucky, Lexington, KY, USA. (15)Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA. (16)Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX, USA. (17)Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. (18)Department of Neurology, University of Michigan, Ann Arbor, MI, USA. (19)Geriatric Research, Education and Clinical Center (GRECC), VA Ann Arbor Healthcare System (VAAAHS), Ann Arbor, MI, USA. (20)Michigan Alzheimer's Disease Center, University of Michigan, Ann Arbor, MI, USA. (21)Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA. (22)Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA. (23)Departments of Neurology, Radiology, and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. (24)Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA. (25)Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. (26)Geriatric Research, Education and Clinical Center (GRECC), University of Wisconsin, Madison, WI, USA. (27)Department of Medicine, University of Wisconsin, Madison, WI, USA. (28)Wisconsin Alzheimer's Disease Research Center, Madison, WI, USA. (29)Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA. (30)Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA. (31)Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. (32)Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA. (33)Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Phoenix, AZ, USA. (34)Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh School of Medicine, Pennsylvania, WA, USA. (35)National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, USA. (36)Department of Psychiatry and Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St. Louis, MO, USA. (37)Department of Psychiatry , University of Texas at Austin/Dell Medical School, Austin, TX, USA. (38)VA Puget Sound Health Care System/GRECC, Seattle, WA, USA. (39)Department of Neurology, University of Washington, Seattle, WA, USA. (40)Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. (41)Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA. (42)Department of Neurology, Mayo Clinic, Rochester, MN, USA. (43)Swedish Medical Center, Seattle, WA, USA. (44)Department of Neurology, University of California San Francisco, San Francisco, CA, USA. (45)Department of Neurosciences, University of California San Diego, La Jolla, CA, USA. (46)Department of Medicine, Duke University, Durham, NC, USA. (47)University of Kansas Alzheimer's Disease Center, University of Kansas Medical Center, Kansas City, KS, USA. (48)Department of Genetics and Genomic Sciences, Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (49)Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (50)Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA. (51)Department of Pathology and Immunology, Washington University, St. Louis, MO, USA. (52)USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, FL, USA. (53)Fred Hutchinson Cancer Research Center, Seattle, WA, USA. (54)Mental Health and Behavioral Science Service, Bruce W. Carter VA Medical Center, Miami, FL, USA. (55)Department of Genetics, University of North Carolina Chapel Hill, Chapel Hill, NC, USA. (56)Neurogenetics Program, University of California Los Angeles, Los Angeles, CA, USA. (57)University of California Los Angeles, University of Southern California, Los Angeles, CA, USA. (58)Section of Gerontology and Geriatric Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA. (59)Department of Medicine, University of Washington, Seattle, WA, USA. (60)Department of Neurology, University of California Irvine, Irvine, CA, USA. (61)Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA. (62)NeuroGenomics and Informatics, Washington University, St Louis, MO, USA. (63)Department of Psychiatry, Washington University in St. Louis, St Louis, MO, USA. (64)Alzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA. (65)Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA. (66)Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, USA. (67)Department of Neurology, University of California Davis, Sacramento, CA, USA. (68)Departments of Neurology, Pharmacology and Neuroscience, Texas Tech University Health Science Center, Lubbock, TX, USA. (69)Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA. (70)Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA. (71)Department of Neurology, Mayo Clinic, Jacksonville, FL, USA. (72)Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA. (73)Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA. (74)Office of Strategy and Measurement, University of North Texas Health Science Center, Fort Worth, TX, USA. (75)Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA. (76)Sanders-Brown Center on Aging, Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA. (77)Department of Neurology, Indiana University, Indianapolis, IN, USA. (78)Department of Psychiatry, New York University, New York, NY, USA. (79)Department of Neurology, University of Louisville School of Medicine, Lousiville, KY, USA. (80)C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Charlestown, MA, USA. (81)Department of Neuroscience, Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (82)Department of Health Behavior and Health Systems, University of North Texas Health Science Center, Fort Worth, TX, USA. (83)Department of Health Management and Policy, School of Public Health, University of North Texas Health Science Center, Fort Worth, TX, USA. (84)Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA. (85)Emory Alzheimer's Disease Center, Emory University, Atlanta, GA, USA. (86)Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA. (87)Department of Radiology, University of Washington, Seattle, WA, USA. (88)Division of Genetics, Department of Medicine and Partners Center for Personalized Genetic Medicine, Division of Genetics, Department of Medicine and Partners Center for Personalized Genetic Medicine, Boston, MA, USA. (89)Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA. (90)Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. (91)Division of Human Genetics, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, UK. (92)Department of Pathology (Neuropathology), University of Pittsburgh, Pittsburgh, PA, UK. (93)UCL Institute of Neurology, University College London, London, England, USA. (94)Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, England, USA. (95)Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA. (96)Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA, USA. (97)Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA. (98)Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. (99)Vanderbilt Memory and Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA. (100)Vanderbilt Genetics Institute, Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. (101)Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA. (102)Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA. (103)Department of Pathology, Duke University, Durham, NC, USA. (104)Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA. (105)Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA. (106)Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. (107)Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St. Louis, MO, USA. (108)Department of Genome Sciences, University of Washington, Seattle, WA, USA. (109)Department of Medicine (Medical Genetics), University of Washington, Seattle, WA, USA. (110)Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA, USA. (111)Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA. (112)Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA. (113)Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA, USA. (114)Department of Neurology, Albert Einstein College of Medicine, New York, NY, USA. (115)Department of Neuroscience, Brigham Young University, Provo, UT, USA. (116)Department of Biology, yBrigham Young University, Provo, UT, USA. (117)Department of Neurology, Oregon Health and Science University, Portland, OR, USA. (118)Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA. (119)Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA. (120)Department of Pathology, Boston University, Boston, MA, USA. (121)Department of Neuropsychology, University of California San Francisco, San Francisco, CA, USA. (122)Department of Epidemiology, University of Washington, Seattle, Seattle, USA. (123)Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA. (124)Department of Neurology, Emory University, Atlanta, GA, USA. (125)National Center for PTSD, Boston VA Healthcare System, Boston, MA, USA. (126)Department of Pathology, University of Michigan, Ann Arbor, MI, USA. (127)National Center for PTSD at Boston VA Healthcare System, Boston, MA, USA. (128)Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. (129)Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA. (130)Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. (131)Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. (132)Department of Medicine - Pulmonary, New York University, New York, NY, USA. (133)Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA. (134)Department of Pathology, University of California San Diego, La Jolla, CA, USA. (135)School of Nursing Northwest Research Group on Aging, University of Washington, Seattle, WA, USA. (136)Pfizer Worldwide Research and Development, New York, NY, USA. (137)Department of Pathology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. (138)Weill Institute for Neurosciences, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA. (139)Department of Pathology, University of Southern California, Los Angeles, CA, USA. (140)Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. (141)Department of Pathology and Laboratory Medicine and Alzheimer's Disease Research Center, University of California Irvine, Irvine, CA, USA. (142)Department of Neurology, Washington University, St. Louis, MO, USA. (143)Department of Psychiatry, Washington University School of Medicine, St. Louis Missouri, USA. (144)Department of Research Regulatory Compliance, College of Medicine, Howard Unviersity, Washington, DC, USA. (145)Institute for Translational Research, University of North Texas Health Science Center, Fort Worth,, TX, USA. (146)Center for Mind and Brain and Department of Neurology, University of California Davis, Sacramento, CA, USA. (147)Center for Population Health and Aging, Texas AandM University Health Science Center, Lubbock , TX, USA. (148)Department of Family and Community Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, USA. (149)Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. (150)Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA. (151)Pacific Health Research & Education Institute, VA Pacific Islands Healthcare System, Honolulu, HI, USA. (152)Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA. (153)Department of Internal Medicine and Geriatrics, University of North Texas Health Science Center, Fort Worth, TX, USA. (154)Department of Medical Education, TCU/UNTHSC School of Medicine, Fort Worth, TX, USA. (155)Arizona Alzheimer's Consortium, Phoenix, AZ, Canada. (156)Banner Alzheimer's Institute, Phoenix, AZ, USA. (157)Department of Psychiatry, University of Arizona, Phoenix, AZ, USA. (158)Alzheimer's Disease Center, New York University, New York, NY, USA. (159)Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA. (160)Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada. (161)Departments of Psychiatry, Medicine, Family and Community Medicine, and the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health Science Center at San Antonio,, San Antonio, TX, Canada. (162)Department of Neurology, Barrow Neurological Institute St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA. (163)Department of Medical Genetics, University of British Columbia, Vancouver, Canada. (164)Department of Radiology and Imaging Sciences, Indiana University, Indianapolis, IN, USA. (165)Department of Pathology (Neuropathology), Rush University Medical Center, Chicago, IL, USA. (166)Department of Psychiatry, University of Southern California, Los Angeles, CA, USA. (167)Cambridge Institute for Medical Research, University of Cambridge, Cambridge, England, USA. (168)Faculty of Medicine, Department of Medicine (Neurology), University of Toronto, Toronto, ON, USA. (169)Maya Angelou Center for Health Equity, Wake Forest School of Medicine, Winston-Salem, NC, USA. (170)Center for Outreach in Alzheimer's, Aging and Community Health at North Carolina A&T State University, Greensboro, NC, USA. (171)Center for Applied Health Research, Baylor Scott & White Health, Temple, TX, USA. (172)Center for Population Health and Aging, Texas A&M University Health Science Center, Lubbock, TX, USA. (173)College of Medicine, Texas A&M University Health Science Center, College Station, TX, USA. (174)Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT, USA. (175)Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA. (176)Renaissance Computing Institute, University of North Carolina Chapel Hill, Chapel Hill, NC, USA. (177)Department of Pathology, Johns Hopkins University, Baltimore, MD, USA. (178)Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, USA. (179)Sanders-Brown Center on Aging, Department of Neuroscience, College of Medicine, University of Kentucky, Kentucky, OH, USA. (180)Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, USA. (181)Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. (182)Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA. (183)Department of Biostatistics, University of Washington, Seattle, WA, USA. (184)Department of Pathology, Oregon Health and Science University, Portland, OR, USA. (185)Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA. (186)Center for Cognitive Neurology and Departments of Neurology and Pathology, New York University Grossman School of Medicine, New York, USA. (187)Evelyn F. McKnight Brain Institute, Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA. (188)Social Sciences & Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA. (189)Department of Ophthalmology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. (190)Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA. (191)Department of Epidemiology, Columbia University, New York, NY, USA. (192)Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. adamnaj@pennmedicine.upenn.edu. (193)Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. adamnaj@pennmedicine.upenn.edu. (#)Contributed equally 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). DOI: 10.1186/s13059-025-03564-z PMCID: PMC12273372 PMID: 40676597 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Ethics approval and consent to participate: For our IRB to compile the de-identified data and conduct analyses, the ADGC protocol is reviewed and approved by the University of Pennsylvania IRB #8 (Federalwide Assurance #00004028). Consent for publication: Not applicable. Competing interests: J.A.P. has received compensation for serving as a section editor for Springer Nature and a grant reviewer with the Department of Defense and Research Grants Council of Hong Kong. M.S.A. is an advisor to Eli Lilly. L.G.A. receives compensation as a consultant for Biogen, Two Labs, IQVIA, NIH, Florida Department of Health, NIH Biobank, Eli Lilly, GE Healthcare, and Eisai; has received compensation for lectures, etc. from AAN, MillerMed, AiSM, and Health and Hospitality; and has received travel and meeting support from the Alzheimer’s Association; she also participates on Data Safety Monitoring or Advisory boards for IQVIA, NIA R01 AG061111, the UAB Nathan Shock Center, and the New Mexico Exploratory ADRC; she has received compensation for leadership roles in the Medical Science Council Alzheimer Association Greater IN Chapter, the Alzheimer Association Science Program Committee, and the FDA PCNS Advisory Committee; she also has stock or stock options Cassava Neurosciences and Golden Seeds; and has received materials support from AVID Pharmaceuticals, Life Molecular Imaging, and Roche Diagnostics. S.E.A. has received honoraria and/or travel expenses for lectures from Abbvie, Eisai, and Biogen and has served on scientific advisory boards of Corte, has received consulting fees from Athira, Cassava, Cognito Therapeutics, EIP Pharma and Orthogonal Neuroscience, and has received research grant support from NIH, Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, Abbvie, Amylyx, EIP Pharma, Merck, Janssen/Johnson & Johnson, Novartis, and vTv. S.Asthana reported receiving grants from National Institute on Aging/National Institutes of Health, Genentech, Merck, Toyoma Chemical, and Lundbeck outside the submitted work. L.L.B. has served as deputy editor for Alzheimer’s and Dementia for the Alzheimer’s Association. D.A.B. is a consultant for Biogen, Inc. B.F.B. has received institutional support from LBDA; is a member of the Scientific Advisory Boards of the Tau Consortium (funded by the Rainwater Charitable Foundation), AFTD, LBDA, and GE Healthcare; is a member of the Data Safety Monitoring Board of trial involving mesenchymal stem cells in MSA. J.D.B has received honoraria from serving on the Scientific Advisory Board and Speaker’s Bureau of Biogen, Celgene, EMD Serono, Genentech and Novartis; has received research support from AbbVie, Alexion, Alkermes, Biogen, Celgene, Sanofi Genzyme, Genentech, Novartis and TG Therapeutics. A.L.B. has received financial support from NIH, the Association for Frontotemporal Degeneration, the Bluefield Project, the Rainwater Charitable Foundation, Regeneron, Eisai and Biogen; and has served as a paid consultant for AGTC, Alector, Amylyx, AviadoBio, Arkuda, Arrowhead, Arvinas, Eli Lilly, Genentech, LifeEdit, Merck, Modalis, Oligomerix, Oscotec, Transposon and Wave. J.M.B. is compensated as a consultant for Stage 2 Innovations; and has received honoraria and travel support for speaking from Astra-Zeneca. J.D.Buxbaum is a consultant to BridgeBio and to Rumi; holds a patent for IGF- 1 in Phelan-McDermid syndrome; holds an honorary professorship from Aarhus University Denmark; receives research support from Takeda and Oryzon; and is a journal editor for Springer Nature. C.Cao has a patent pending for melatonin-insulin-THC (MIT) treatment; and serves as a scientific consultant for MegaNano Biotech, Inc. C.M.C. has received grants from the National Institutes of Health, Eisai, Eli Lilly, Veterans Affairs; has received nonfinancial support from Amarin; has received data safety monitoring board/travel/advisory board honoraria from Alzheimer's Association, National Institutes of Health, and American Fed Aging Res Beeson Program. J.C. is currently employed as a senior scientist at Takeda Pharmaceuticals, Inc.; the company did not influence the study design, analyses, or interpretation of the results presented in this manuscript. C.Cruchaga has received research support from GSK and Eisai, is a member of the advisory boards of Vivid Genomics and Circular Genomics, and owns stocks. D.W.D. is an editorial board member for Acta Neuropathologica, Brain, Brain Pathology, Neuropathology and Applied Neurobiology, Annals of Neurology, Neuropathology, and is an Editor for the International Journal of Clinical and Experimental Pathology and for the American Journal of Neurodegenerative Disease; and receives support Mangurian Foundation and the Rainwater Charitable Foundation. R.S.D. is an employee of F. Hoffman-La Roche, Ltd. and Genentech, Inc.; and owns or has stock options in F. Hoffmann-La Roche, Ltd. N.E.-T. receives research support from the NIH; is a member of multiple Scientific Advisory Boards including the Framingham Heart Study Executive Committee, Cytox, and the NIH TREAT-AD Consortium External Advisory Board Member; has patents pending for Human Monoclonal Antibodies Against Amyloid Beta Protein and Their Use as Therapeutic Agents Application, and RNAi against targets in Progressive Supranuclear palsy; is an Editorial Board Member for the American Journal of Neurodegenerative Disease and Alzheimer's & Dementia; and receives research support from Florida Health Ed and Ethel Moore Alzheimer's Disease Research Program and an Alzheimer's Association Zenith Award. T.M.F. has received honoraria and travel support from the External Advisory Boards for Alzheimer Disease Research Centers that might also be a site for the LEADS study. D.R.G. serves on Data Safety Monitoring Boards for Cognition Therapeutics and Proclara Biosciences; and is an Editor of Alzheimer’s Research & Therapy. B.G. has consulted for Piramal Imaging. A.M.G is a member of the Scientific Advisory Boards/Scientific Research Boards for Genentech, Muna Therapeutics, and Denali Therapeutics. N.R.G.-.R. has received royalties for an article in UpToDate; and has received research support for multi-center studies at Eli Lilly & Company, Biogen, and AbbVie. R.C.G. has received compensation as an advisor for AIA, Grail, Humanity, Kneed Media, Plumcare, UnitedHealth, Verily, VibrentHealth, Wamberg; and is co-founder of Genome Medical, Inc. J.Hardy is supported by the UK Dementia Research Institute, which receives its funding from DRI, Ltd., funded by the UK Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK; and is also supported by the MRC, Wellcome Trust, the Dolby Family Fund, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre. T.H. is a member of a scientific advisory board for Vivid Genomics. L.S.H. is the Web Editor for JAMA Neurology. B.T.H. has a family member who works at Novartis, and owns stock in Novartis; and serves on the Scientific Advisory Board of Dewpoint and owns stock; and serves on a Scientific Advisory Board or is a consultant for AbbVie, Aprinoia Therapeutics, Arvinas, Avrobio, Axial, Biogen, BMS, Cure Alz Fund, Cell Signaling, Eisai, Genentech, Ionis, Latus, Novartis, Sangamo, Sanofi, Seer, Takeda, the US Dept of Justice, Vigil, Voyager; and receives research support for his laboratory from research grants from the National Institutes of Health, Cure Alzheimer’s Fund, Tau Consortium, and the JPB Foundation, and through sponsored research agreements from Abbvie, BMS, and Biogen. G.P.J. was the 2022 Past President of the American Society of Human Genetics. J.H.K. has been a consultant for Biogen. E.B.L. receives royalties from contributions to UpToDate. J.B.L. is a member of the Scientific Advisory Board of Vaxxinity and has received grant support from Biogen and GE Healthcare. A.I.L. is a founder of EmTheraPro. R.B.L. has received research support from the National Institutes of Health, the FDA, and the National Headache Foundation; serves as consultant, advisory board member, or has received honoraria or research support from AbbVie/Allergan, Amgen, Biohaven, Dr. Reddy’s Laboratories (Promius), electroCore, Eli Lilly, GlaxoSmithKline, Lundbeck, Merck, Novartis, Teva, Vector, and Vedanta Research; receives royalties from Wolff’s Headache, 8 th edition (Oxford University Press, 2009), and Informa; and holds stock in Biohaven and Manistee. D.C.M. receives NIH funding; is the inventor of the FCI-SF and the UAB Research Foundation (UABRF); owns the FCI-SF through copyright and trademark (FCAP); has previously received royalty and consulting income from UABRF licensed use and sale of the FCI-SF; and is currently a consultant on an unaffiliated NIH grant using the FCI-SF. A.V.M. is a council member of the Alzheimer's Association International Research Grants Program, on the steering committee of the Alzheimer's Disease Cooperative Study, and on the editorial boards of Alzheimer's & Dementia: Translational Research and Clinical Interventions and the Journal of Neuro-ophthalmology. S.I.M. is an employee of Pfizer, Inc.; the company did not influence the study design, analyses, or interpretation of the results presented in this manuscript. B.L.M. has received grant support from NIH, the Bluefield Project, and the Rainwater Charitable Foundation; has received royalties from books published by Cambridge University Press, Elsevier, Inc., Guilford Publications, Inc., Johns Hopkins Press, Oxford University Press and Taylor & Francis Group; has received honorarium for serving as a member of the Scientific Advisory Board of the Alzheimer’s Disease Research Center (ADRC) at Massachusetts General Hospital, Stanford University, and the University of Washington; and has received consulting fees from Genworth. J.W.M. receives compensation as Associate Editor for the journal Nutrition Reviews; and has received within the last 3 years consulting compensation from Church and Dwight, Inc.; and is a producer and seller of consumer goods including vitamin supplements. J.C.M is a consultant for clinical trials of antidementia drugs from Eli Lilly and Company, Biogen, and Janssen; is a consultant for the Barcelona Brain Research Center (BBRC) and the TS Srinivasan Advisory Board; is an advisory board member for the Cure Alzheimer’s Fund Research Strategy Council. S.E.O. has multiple pending and issued patents on blood biomarkers for detecting and precision medicine therapeutics in neurodegenerative diseases; and is a founding scientist of Cx Precision Medicine, Inc. and owns stock options. R.C.P. is chair for the data monitoring committee for Pfizer and Janssen Alzheimer Immunotherapy and is a consultant for GE Healthcare and Roche. W.W.P. is a co-inventor of and holds a patent for WO/2018/160496, related to the differentiation of human pluripotent stem cells into microglia. E.M.R. is a scientific advisor to Alzheon, Aural Analytics, Denali, Retromer Therapeutics, and Vaxxinity and a co-founder and advisor to ALZPath. J.M.R. receives research support from Avid Pharmaceuticals. R.N.R. is the Editor of JAMA Neurology. M.S. has received grants from the Icahn School of Medicine at Mount Sinai and the US Department of Veterans Affairs Veterans Health Administration. A.J.S. has received support from Avid Radiopharmaceuticals, a subsidiary of Eli Lilly (in-kind contribution of PET tracer precursor), is a member of scientific advisor boards for Bayer Oncology and Eisai and of the dementria advisory board and Siemens Medical Solutions USA, is a member of the National Heart, Lung, and Blood Institute MESA observational study monitoring board, and is part of the editorial office support as editor-in-chief for Brain Imaging and Behavior for Springer-Nature Publishing. J.A.S. has received consulting fees from AVID, Alnylam Pharmaceuticals, and Cerveau Technologies. L.S.S. has received personal fees from AC Immune, Athira, BioVie, Eli Lilly, Lundbeck, Merck, Neurim Ltd., Novo-Nordisk, Otsuka, Roche/Genentech within the past year; and research grants from Biogen, Eisai, and Eli Lilly and Company. W.W.S. serves as a paid consultant to Biogen Idec and has received grant support from NIH, the Association for Frontotemporal Degeneration, the Bluefield Project, the Rainwater Charitable Foundation, and the Chan-Zuckerberg Initiative. S.A.S. has received an unrestricted research grant from Mars, Inc. R.A.S. has received grants from the National Institutes of Health and the from Concussion Legacy Foundation; and received compensation from Biogen and Lundbeck; and has received royalties received from Psychological Assessment Resources for published neuropsychological tests; and has stock options as a member of the board of King Devick Technologies. D.L.S. has received research support from NIH and Eisai, has participated as a paid member of a DSMB or adjudication committee with Acadia, Avanir, Janssen, and Otsuka, and has received consulting fees from Avanir and NovoNordisk. R.E.T. has received patents for gamma-secretase modulators for exploring treatment of Alzheimer's disease. H.W. has received support from the TEVA speaker's bureau. T.S.W. is as a cofounder of revXon. C.B.W. has received royalties from UpTo Date for 2 chapters; has done legal consulting for the law firms of Abali, Milne, and Faegre Baker Daniels; is a consultant for Merck and Co; and does stroke adjudication for a National Institutes of Health clinical trial. L.A.F. has received institutional support from Mass Mutual Insurance. G.T., W.-P.L., Y.Y.L., P.P.K., J.B.M., J.A.P., R.M.S., X.Z., M.S.A., R.L.A., L.G.A., S.E.A., S.Asthana, C.T.B., R.C.B., L.L.B., S.B., T.G.B., J.T.B., D.Beekly, B.B., D.Bennett, T.D.B., D.A.B., B.F.B., J.D.B., A.L.B., J.M.B., J.D.Buxbaum, C.Cao, C.S.C., C.M.C., M.M.C., H.C.C., S.Craft, P.K.C., E.A.C., C.Cruchaga, M.L.C., P.L.D., C.D., J.C.D., M.Dick, D.W.D., R.S.D., R.D., N.E.-T., D.A.E., D.W.F., V.F., T.M.F., M.P.F., D.R.G., A.G., M.G., D.H.G., B.G., A.M.G., N.R.G.-R., R.C.G., H.H., O.Harari, J.Hardy, T.H., L.S.H., R.M.H., M.J.H., B.T.H., G.P.J., M.I.K., A.K., J.S.K., J.A.K., C.D.K., A.Khaleeq, N.W.K., J.H.K., W.K., E.B.L., J.B.L., A.I.L., A.P.L., R.B.L., M.W.L., O.L.L., K.L.L., C.G.L., M.E.F., D.C.M., E.R.M., D.C.Mash, E.M., A.V.M., W.C.M., A.C.M., M.Mesulam, B.L.M., C.A.M., J.W.M., T.J.M., J.C.M., S.Mukherjee, A.J.M., S.E.O., H.L.P., V.P., E.P., R.C.P., W.W.P., E.M.R., J.M.R., E.D.R., M.Rodriguear, R.N.R., M.S., A.J.S., J.A.S., L.S.S., W.W.S., S.A.S., R.A.S., S.M.S., D.S., R.E.T., D.W.T., V.M.VD., L.J.VE., J.M.V., B.N.V., E.M.W., T.S.W., C.B.W., S.G.Y., B.W.K., W.B., L.-S.W., L.A.F., J.L.H., R.M., M.A.P.-V., G.D.S., G.R.J., C.R., and A.C.N. have received grant funding from the National Institutes of Health, including from the National Institute on Aging and others. E.R. has received grant funding from the Canadian Institutes for Health Research.
15. Front Sports Act Living. 2025 Jun 23;7:1594733. doi: 10.3389/fspor.2025.1594733. eCollection 2025. Adjuvant melatonin therapy during exercise prescription in breast cancer survivors on physical and anthropometric parameters, quality of life, and hormonal response. A randomized controlled trial. Celorrio San Miguel AM(1), Cacharro LM(2), Santamaría G(3), Garrosa M(4)(5), Celorrio San Miguel M(6), Roche E(7)(8)(9)(10), Garrosa E(11), Fernández-Lázaro D(4)(5)(10). Author information: (1)Doctoral School, University of Leon, Leon, Spain. (2)Department of Ophthalmology of Salamanca University Assistance Complex (CAUSA), Salamanca University Hospital, Salamanca, Spain. (3)Department of Anatomy and Radiology, Faculty of Health Sciences, University of Valladolid, Soria, Spain. (4)Area of Histology, Faculty of Medicine, Institute of Neurosciences of Castile and Leon (INCYL), University of Valladolid, Valladolid, Spain. (5)Neurobiology Research Group, Faculty of Medicine, University of Valladolid, Valladolid, Spain. (6)Emergency Department, Línea de la Concepción Hospital, La Línea de la Concepción, Spain. (7)Department of Applied Biology-Nutrition, Institute of Bioengineering, Miguel Hernández University, Elche, Spain. (8)Group 36 - Nutrition and Physical Activity for Health, Alicante Institute of Health and Biomedical Research (ISABIAL), Alicante, Spain. (9)CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Carlos III Health Institute (ISCIII), Madrid, Spain. (10)Nutrition and Physical Activity Research Group, Spanish Nutrition Society (SEÑ), Madrid, Spain. (11)Faculty of Psychology, University of Salamanca, Salamanca, Spain. 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 activity program, had not significant (p > 0.05) effects on anthropometry, physical condition, health-related quality of life and hormonal response compared to the placebo group. Our findings suggest no clear effect of melatonin in post-treatment for BCS in the mentioned parameters. Further clinicals trials are recommended to establish definitive recommendations for physical activity and melatonin supplementation in BCS. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov, identifier (NCT06696378). © 2025 Celorrio San Miguel, Cacharro, Santamaría, Garrosa, Celorrio San Miguel, Roche, Garrosa and Fernández-Lázaro. DOI: 10.3389/fspor.2025.1594733 PMCID: PMC12229996 PMID: 40625889 Conflict of interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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