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# Research Synthesis: Melatonin Aging — full paper ## Abstract This synthesis tests the thesis that evidence for Melatonin aging is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation. Endogenous melatonin declines with chronological age, yet whether exogenous supplementation slows aging-related functional deterioration remains an unsettled question of translational relevance. This synthesis employed AI-assisted screening and dual-adjudication of randomized trials, meta-analyses, and controlled cohorts identified through structured evidence-retrieval protocols, with every included claim traced to an included source in an auditable evidence trail. In sum, the current evidence supports melatonin's short-term anti-inflammatory and antioxidant activity in perioperative and dialysis settings but does not yet demonstrate durable anti-aging functional benefit in community-dwelling older adults; randomized trials powered for hard clinical endpoints, such as mobility, cognitive trajectories, and mortality, with standardized dosing are needed to define the boundary conditions under which melatonin supplementation may attenuate age-related decline. **Evidence-abstraction note.** The 50 retained reference papers are not 50 independent primary clinical trials: 46 are review, indirect, or mechanistic source-level summaries, and 4 are classified as direct interventional evidence. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence. ## Methods ### Review type and protocol This manuscript is reported as a Thin-corpus evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-melatonin_aging-v06-DAILY-2026-06-02T01-57-50Z`. ### Information sources Sources were retrieved across PubMed, Europe PMC, OpenAlex, Semantic Scholar, Crossref, DOAJ, OpenAIRE, PMC OAI, bioRxiv, medRxiv, arXiv, and ClinicalTrials.gov. Retrieval window: 2026-06-02. ### Search strategy The following topic-anchored queries were executed against the information sources listed above: - `melatonin aging AND aging AND human` - `melatonin aging AND older adults` - `melatonin aging AND randomized controlled trial` - `melatonin AND aging AND human` - `melatonin AND older adults` - `melatonin AND randomized controlled trial` - `circadian hormone AND aging AND human` - `circadian hormone AND older adults` - `circadian hormone AND randomized controlled trial` - `sleep aging AND aging AND human` ### Eligibility criteria - Sources whose primary content addresses melatonin aging. - Sources with extractable quantitative or qualitative findings. - Peer-reviewed primary research, systematic reviews, or meta-analyses; preprints accepted only when source-traceable. - Sources with verifiable bibliographic identifiers (DOI / PMID / canonical handle). ### Selection of sources of evidence The synthesis did not begin from an unfiltered database export. It began from a pre-curated receipt-candidate set generated by the retrieval and claim-binding pipeline. Of 188 records in the receipt-candidate union, 68 were classified as source candidates and 50 were admitted as traceable synthesis sources. Mixed partial-or-none and partial-only rows are separate claim-binding audit buckets, not additive exclusion totals. No additional records were excluded after final source admission. ### source admission funnel | Admission bucket | n | |---|---:| | Receipt candidate union | 188 | | Classified source candidates | 68 | | No extractable claims | 27 | | None-only claim binding | 4 | | Mixed partial-or-none claim-binding candidates | 67 | | Partial-only claim-binding candidates | 13 | | Strict high-confidence sources | 9 | | Admitted final sources | 50 | ### Exclusion reasons - Non-traceable findings (claim could not be linked to source text): 0 records. - Wrong population / off-topic sources excluded at screening. - Duplicate records deduplicated by DOI / PMID before screening. ### Data items The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text. ### Risk-of-bias appraisal Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`. ### Synthesis approach Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, dosing and pharmacokinetics, immune and inflammation, longevity, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates. ### AI-use disclosure Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified. ### Accountability Accountability is established through reproducible artifacts: a deterministic protocol (`methods_pack.json`), a complete claim and citation registry, extracted numeric trace, deterministic gates (`full_paper.journal_surface.json`, `pre_submit_gate.json`, `artifact_consistency.json`), and a versioned correction path documented in the run's submission record. This run is certified under the `researka_agent_certified` accountability model — trust is machine-verifiable rather than dependent on author signoff. ## Results **Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim. | Outcome class | Corpus slice | Strongest signal | Directness | Main limitation | |---|---|---|---|---| | Contextual Adjacent Evidence | n=30; claims=1719 | no extracted directional signal in 25/30 sources | 1 direct; 17 indirect; 12 review | limited corpus depth in this outcome class | | Dosing and Pharmacokinetics | n=10; claims=493 | no extracted directional signal in 9/10 sources | 1 direct; 2 indirect; 7 review | limited corpus depth in this outcome class | | Cardiometabolic | n=5; claims=753 | unclear signal in 2/5 sources | 2 direct; 2 indirect; 1 review | limited corpus depth in this outcome class | | Safety and Comorbidity | n=2; claims=31 | unclear signal in 1/2 sources | 1 indirect; 1 review | limited corpus depth in this outcome class | | Deficiency Prevalence | n=1; claims=7 | no extracted directional signal in 1/1 sources | 1 indirect | single-source slice; hypothesis-generating | | Immune and Inflammation | n=1; claims=1 | no extracted directional signal in 1/1 sources | 1 indirect | single-source slice; hypothesis-generating | | Longevity | n=1; claims=4 | positive signal in 1/1 sources | 1 review | single-source slice; hypothesis-generating | This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate. ### Contextual Adjacent Evidence Outcomes 30 included sources were assigned to this outcome class. Directional coding: mixed=1, null=25, unclear=4. Directness coding: direct=1, indirect=17, review=12. ### Dosing Pharmacokinetics Outcomes 10 included sources were assigned to this outcome class. Directional coding: null=9, unclear=1. Directness coding: direct=1, indirect=2, review=7. ### Cardiometabolic Outcomes Cardiometabolic remains a separate Results slice (n=5; claims=753; unclear signal in 2/5 sources; 2 direct; 2 indirect; 1 review; limited corpus depth in this outcome class) and is not pooled into adjacent endpoint classes. ### Safety Comorbidity Outcomes 2 included sources were assigned to this outcome class. Directional coding: null=1, unclear=1. Directness coding: indirect=1, review=1. ### Deficiency Prevalence Outcomes 1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1. ### Immune Inflammation Outcomes 1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1. ### Longevity Outcomes 1 included source were assigned to this outcome class. Directional coding: positive=1. Directness coding: review=1. ## Limitations **Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim. The curated corpus, while comprising approximately 50 reference papers, contains no long-term mortality randomised controlled trial specifically designed to test whether melatonin supplementation extends lifespan or reduces all-cause mortality in non-diabetic, community-dwelling older adults. Consequently, the headline conclusion that melatonin's anti-ageing case is 'incomplete' rests partly on the absence, rather than the presence, of disconfirming evidence — a structural gap that limits causal inference. No cohort study in the corpus tracked participants beyond a follow-up window typical of acute or perioperative interventions (most lasting weeks to a few months), meaning that whether the cardiometabolic and anti-inflammatory signals documented in short-duration trials would persist over years remains entirely unknown. This temporal limitation means that the synthesis cannot adjudicate whether melatonin's mechanistic promise — free-radical scavenging, mitochondrial support, circadian re-entrainment — translates into durable healthspan gains. In sum, the absence of multi-year, hard-endpoint RCTs is the most consequential gap in this evidence base. The population profiles of the included trials constrain external validity in important ways. Most randomised evidence in the corpus was gathered from adults undergoing acute medical or surgical events — coronary artery bypass grafting (Casper 2024, n = 17 in the melatonin arm; Mohammadi 2025, n = 20 per arm), peritoneal dialysis (Movahedian 2025), and mechanically ventilated ICU patients (Dessap 2025). These populations are not representative of the ambulatory older adults in whom anti-ageing interventions are most commonly considered. None of these populations inform the question of whether melatonin slows biological ageing in otherwise healthy adults over 60. Geographic and ethnic diversity is also limited: the majority of trials were conducted in single-centre settings in specific countries, and the corpus contains no large, multi-national, pragmatic effectiveness trial. The Parkinson's disease evidence — Badran 2025's pooled analysis reporting mixed motor and sleep outcomes — and the multiple sclerosis safety data from Bejarano 2026 further underscore that the corpus spans neurodegenerative conditions without adequately powered geriatric samples. As a result, the synthesised evidence likely over-represents acute-intervention contexts and under-represents the chronic, community-dwelling ageing population of primary clinical interest. A substantial fraction of the evidence base rests on mechanistic or pre-clinical plausibility rather than direct clinical demonstration of anti-ageing effects, creating a mechanism-to-clinic gap that the current corpus cannot bridge. Carrillo-Vico 2013, the oldest paper in the corpus, provides a narrative review of melatonin's immune-buffering functions across gastrointestinal, skin, and retinal tissues but enrolled no clinical population and generated no extractable effect estimates. Shang 2024's review of antioxidants and ovarian aging similarly includes melatonin in a broader antioxidant framework, but the extractable data are dominated by CoQ10 subgroup analyses, making the melatonin-specific signal difficult to isolate. Until mechanistic findings are tested in trials designed with ageing-specific primary endpoints — and with follow-up periods commensurate with the slow trajectory of biological ageing — the anti-ageing hypothesis for melatonin remains biologically plausible but clinically unproven. ## Conclusion For melatonin aging, the final interpretation is deliberately tiered: the retained clinical and adjacent evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct clinical records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation. The current corpus may support melatonin aging as a general health or lifestyle intervention where otherwise indicated, but does not justify marketing it as a standalone geroprotective or anti-aging intervention with proven hard-longevity effects. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging. ## What This Synthesis Adds This synthesis maps 50 included sources on Melatonin aging across 7 outcome classes and 487 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit. Across 50 curated reference papers, the evidence base for Melatonin aging shows a context-dependent profile. Positive signals appear in: cardiometabolic, longevity. Null findings dominate: contextual other, dosing pharmacokinetics. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Melatonin aging anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established. The strongest unresolved contrast is the disagreement between Shang 2024 and SanchezGarcia 2026 on contextual adjacent evidence (severity 4/5), which defines the boundary condition future studies must test rather than smooth over. Prior reviews in the corpus (Mohammadi 2025b) emphasize convergent signals on Melatonin aging. This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary. ### Boundary-Condition Matrix | Outcome class | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary | |---|---:|---:|---|---| | longevity | 0 | 1 | positive | direct clinical gap | | cardiometabolic | 2 | 3 | mixed, positive, unclear | conflict-resolution gap | | safety and comorbidity | 0 | 2 | null, unclear | direct clinical gap | | deficiency prevalence | 0 | 1 | null | direct clinical gap | | immune and inflammation | 0 | 1 | null | direct clinical gap | | contextual adjacent evidence | 1 | 29 | mixed, null, unclear | conflict-resolution gap | | dosing and pharmacokinetics | 1 | 9 | null, unclear | replication gap | ### Evidence-Gap Priority | Priority | Gap | Rationale | |---|---|---| | P1 | longevity: direct clinical gap | 0 direct and 1 indirect source; direction profile: positive | | P2 | cardiometabolic: conflict-resolution gap | 2 direct and 3 indirect sources; direction profile: mixed, positive, unclear | | P3 | safety and comorbidity: direct clinical gap | 0 direct and 2 indirect sources; direction profile: null, unclear | | P4 | deficiency prevalence: direct clinical gap | 0 direct and 1 indirect source; direction profile: null | | P5 | immune and inflammation: direct clinical gap | 0 direct and 1 indirect source; direction profile: null | ### Next-Study Design Recommendation The next high-yield study for Melatonin aging should target the **longevity** evidence gap, pre-register the primary endpoint, separate clinical from mechanistic endpoints, preserve safety and adherence capture, and include an analysis plan that can falsify the current boundary-condition claim rather than only confirming a favorable direction. Minimum useful design: at least 200 participants per arm, a priority population of adults or older adults with baseline risk in the target outcome domain, and follow-up lasting at least 12 months; shorter or smaller studies should be treated as hypothesis-generating. ## Evidence Snapshot The manuscript foregrounds the load-bearing evidence; the full evidence tables remain in the supplement. ### Load-Bearing Included Studies - Movahedian 2025; RCT (clinical); tier=A1; directness=direct; population=adults; endpoint=cardiometabolic; direction=positive; representative statistic=P = 0.001. - Casper 2024; RCT (clinical); tier=A1; directness=direct; population=adults; endpoint=cardiometabolic; direction=positive; representative statistic=P = 0.0001. - Sayed 2026; RCT (clinical); tier=A1; directness=direct; population=adults; endpoint=contextual other; direction=null; representative statistic=P = 0.005. - Bejarano 2026; RCT (clinical); tier=A1; directness=direct; population=adults; endpoint=dosing pharmacokinetics; direction=unclear. - Mohammadi 2025b; Review / meta-analysis; tier=B1; directness=review; population=—; endpoint=cardiometabolic; direction=mixed; representative statistic=P < 0.001. - Mohammadi 2025; Observational; tier=B2; directness=indirect; population=adults; endpoint=cardiometabolic; direction=unclear; representative statistic=P < 0.001. - Badran 2025; Observational; tier=B2; directness=indirect; population=adults; endpoint=contextual other; direction=null; representative statistic=P = 0.002. - Pratap 2025; Observational; tier=B2; directness=indirect; population=adults; endpoint=contextual other; direction=null; representative statistic=P > 0.05. - Shang 2024; Observational; tier=B2; directness=review; population=—; endpoint=contextual other; direction=unclear; representative statistic=P < 0.0001. - Butler 2025; Observational; tier=B2; directness=indirect; population=adults; endpoint=contextual other; direction=null; representative statistic=P < 0.05. ### Load-Bearing Tensions - Severity 4 disagreement: Shang 2024 vs SanchezGarcia 2026; Shang 2024 (unclear) vs SanchezGarcia 2026 (mixed) on contextual other - Severity 4 disagreement: Sadeghpour 2025 vs SanchezGarcia 2026; Sadeghpour 2025 (null) vs SanchezGarcia 2026 (mixed) on contextual other - Severity 4 disagreement: Tavares 2024 vs SanchezGarcia 2026; Tavares 2024 (unclear) vs SanchezGarcia 2026 (mixed) on contextual other - Severity 4 disagreement: Casper 2024 vs Mohammadi 2025b; Casper 2024 (positive) vs Mohammadi 2025b (mixed) on cardiometabolic - Severity 4 disagreement: Pratap 2025 vs SanchezGarcia 2026; Pratap 2025 (null) vs SanchezGarcia 2026 (mixed) on contextual other - Severity 4 disagreement: Khaled 2025 vs SanchezGarcia 2026; Khaled 2025 (null) vs SanchezGarcia 2026 (mixed) on contextual other - Severity 4 disagreement: AL-agooz 2025 vs SanchezGarcia 2026; AL-agooz 2025 (null) vs SanchezGarcia 2026 (mixed) on contextual other - Severity 4 disagreement: Al-Maqbali 2025 vs SanchezGarcia 2026; Al-Maqbali 2025 (unclear) vs SanchezGarcia 2026 (mixed) on contextual other Additional corpus sources informed the synthesis without anchoring a foregrounded quantitative claim and are catalogued for completeness: Ayeni 2025, Synnott 2025, Alawi 2026, Wu 2026, Guo 2026, Asla 2025, Fiori 2026, Leung 2025, Du 2026, Pang 2025, Kracht 2026, Li 2025, Giorgis 2025, Abuhassan 2026, Wu 2025, Oda 2025, Ginzac 2025, Saraiva 2026, Suram 2025, Alghamdi 2026, Bradfield 2025, Haq 2025, Queiroz 2025, Akhavan 2026, Gupta 2025, Esmaeilzadeh 2025, Lv 2025, Nofal 2026, Kilic 2025, Liu 2025, Chen 2025, Qin 2025, ADA 2024. ## References - **Mohammadi 2025.** _Melatonin administered postoperatively lowers oxidative stress and inflammation and significantly recovers heart function in patients undergoing CABG surgery._ European Journal of Medical Research, 2025. DOI: 10.1186/s40001-025-02789-9. PMID: 40619439. - **Movahedian 2025.** _Effects of melatonin on advanced glycation end products, inflammation, and oxidative stress in peritoneal dialysis patients: a randomized controlled trial._ Scientific Reports, 2025. DOI: 10.1038/s41598-025-20792-2. PMID: 41125682. - **Badran 2025.** _Exploring the role of melatonin in managing sleep and motor symptoms in Parkinson’s disease: a pooled analysis of double-blinded randomized controlled trials._ Neurological Sciences, 2025. DOI: 10.1007/s10072-025-08221-8. PMID: 40387966. - **Mohammadi 2025b.** _Comprehensive Effects of Melatonin Supplementation on Cardiometabolic Risk Factors: A Systematic Review and Dose–Response Meta-Analysis._ Nutrients, 2025. DOI: 10.3390/nu18010134. - **Pratap 2025.** _Evaluation of melatonin gel as local drug delivery system for the treatment of periodontitis: a split-mouth randomized controlled trial._ BMC Oral Health, 2025. DOI: 10.1186/s12903-025-05598-y. PMID: 39948592. - **Shang 2024.** _Antioxidants and Fertility in Women with Ovarian Aging: A Systematic Review and Meta-Analysis._ Advances in Nutrition, 2024. DOI: 10.1016/j.advnut.2024.100273. PMID: 39019217. - **Casper 2024.** _Melatonin ameliorates inflammation and improves outcomes of ischemia/reperfusion injury in patients undergoing coronary artery bypass grafting surgery: a randomized placebo-controlled study._ Apoptosis, 2024. DOI: 10.1007/s10495-024-02040-6. PMID: 39633112. - **Butler 2025.** _A Series of Personalized Melatonin Supplement Interventions for Poor Sleep: Feasibility Randomized Crossover Trial for Personalized N-of-1 Treatment._ JMIR Formative Research, 2025. DOI: 10.2196/58192. PMID: 41004640. - **Sayed 2026.** _Evaluating the antioxidant and anti-inflammatory effect of melatonin in pediatric hemodialysis patients: a randomized, placebo-controlled trial._ Scientific Reports, 2026. DOI: 10.1038/s41598-025-34264-0. PMID: 41565787. - **Ayeni 2025.** _Pharmacologic neuroprotective agents for the treatment of perinatal asphyxia in low-income and lower-middle-income countries: A systematic review and meta-analysis of randomised controlled trials._ PLOS One, 2025. DOI: 10.1371/journal.pone.0337798. PMID: 41343532. - **Tavares 2024.** _Effect of melatonin on postoperative cognitive function in elderly patients submitted to transurethral resection of the prostate under spinal anesthesia ☆._ Clinics, 2024. DOI: 10.1016/j.clinsp.2024.100562. PMID: 39729834. - **Synnott 2025.** _Melatonin agonist tasimelteon (HETLIOZ ® ) improves sleep in patients with primary insomnia: A multicenter, randomized, double-blind, placebo-controlled trial._ PLOS One, 2025. DOI: 10.1371/journal.pone.0332366. PMID: 40971945. - **Alawi 2026.** _Effect of melatonin versus placebo for the prevention of delirium among medically hospitalised older patients: a double-blinded randomised controlled trial (project RESTORE)._ BMJ Open, 2026. DOI: 10.1136/bmjopen-2025-107775. PMID: 41592826. - **Bejarano 2026.** _Hepatic Safety of Adjunctive High-Dose Melatonin in Participants Receiving Ocrelizumab for Primary Progressive Multiple Sclerosis: Liver Toxicity Findings from a Phase I/II Randomised Clinical Trial (MELATOMS-1)._ CNS Drugs, 2026. DOI: 10.1007/s40263-025-01261-w. PMID: 41706381. - **Wu 2026.** _Melatonin supplementation reduces delirium incidence in critically ill patients: a systematic review and meta-analysis._ Frontiers in Pharmacology, 2026. DOI: 10.3389/fphar.2026.1728873. PMID: 41602948. - **Guo 2026.** _Timing-dependent effects of melatonin supplementation on exercise performance and exercise-induced muscle damage: a systematic review and meta-analysis._ Frontiers in Nutrition, 2026. DOI: 10.3389/fnut.2026.1742464. PMID: 41769636. - **Dessap 2025.** _Melatonin for prevention of delirium in patients receiving mechanical ventilation in the intensive care unit: a multiarm multistage adaptive randomized controlled clinical trial (DEMEL)._ Intensive Care Medicine, 2025. DOI: 10.1007/s00134-025-08002-z. PMID: 40608082. - **Asla 2025.** _Melatonin as a Possible Stimulus to Unmask an Oxytocin-Deficient State in Hypopituitarism and Hypothalamic Damage._ The Journal of Clinical Endocrinology and Metabolism, 2025. DOI: 10.1210/clinem/dgaf201. PMID: 40166823. - **SanchezGarcia 2026.** _Oral Melatonin in Critically Ill Patients With COVID‐19: A Quasi‐Experimental Pragmatic Trial._ Journal of Medical Virology, 2026. DOI: 10.1002/jmv.70807. PMID: 41532840. - **Al-Maqbali 2025.** _Effect of melatonin versus placebo for prevention of delirium among medically hospitalised patients: study protocol for a single-centre, double-blinded, randomised controlled trial (project RESTORE)._ BMJ Open, 2025. DOI: 10.1136/bmjopen-2024-094195. PMID: 40000080. - **Fiori 2026.** _Sleep quality and sleepiness in adults with multiple myeloma. Is melatonin a potential treatment?._ Physiological Reports, 2026. DOI: 10.14814/phy2.70805. PMID: 41814853. - **Leung 2025.** _Effect of melatonin on cognitive function in adults with cognitive impairment: a multi-dimensional meta-analysis of randomized trials._ Alzheimer's Research & Therapy, 2025. DOI: 10.1186/s13195-025-01881-w. PMID: 41185054. - **Du 2026.** _A systematic review and meta-analysis of randomized controlled trials investigated the effects of melatonin supplementation on bone mineral density, quality of life, and sleep in menopausal women._ Frontiers in Nutrition, 2026. DOI: 10.3389/fnut.2026.1687221. PMID: 41693954. - **Pang 2025.** _Acute High Dose Melatonin for Encephalopathy of the Newborn (ACUMEN) Study: a protocol for a multicentre phase 1 safety trial of melatonin to augment therapeutic hypothermia for moderate/severe hypoxic ischaemic encephalopathy._ BMJ Open, 2025. DOI: 10.1136/bmjopen-2025-107083. PMID: 40846329. - **Kracht 2026.** _Melatonin Use in Young Children._ JAMA Network Open, 2026. DOI: 10.1001/jamanetworkopen.2025.51958. PMID: 41481289. - **Li 2025.** _Transcutaneous auricular vagal nerve stimulation improves functional dyspepsia with sleep disturbance via enhanced vagal activity: a randomized controlled trial._ International Journal of Surgery (London, England), 2025. DOI: 10.1097/JS9.0000000000003296. PMID: 40905853. - **Khaled 2025.** _Melatonin for preventing postoperative delirium in elderly patients: A multicenter randomized placebo-controlled pilot study._ Medicine, 2025. DOI: 10.1097/MD.0000000000041615. PMID: 39998812. - **Giorgis 2025.** _A prospective randomized crossover trial investigating melatonin versus sleep deprivation for sleep induction in nap electroencephalography._ Epilepsia Open, 2025. DOI: 10.1002/epi4.70169. PMID: 41208640. - **Abuhassan 2026.** _The effect of melatonin supplementation on lipid profile, oxidative stress, inflammatory marker, and sleep quality in patients with chronic kidney disease: a GRADE assessed meta-analysis._ Frontiers in Nutrition, 2026. DOI: 10.3389/fnut.2026.1772877. PMID: 41727206. - **Wu 2025.** _Melatonin improved the outcomes of women with ART: a systematic review and meta-analysis of randomized trials._ Frontiers in Reproductive Health, 2025. DOI: 10.3389/frph.2025.1680984. PMID: 41064014. - **Oda 2025.** _Exogenous melatonin boosts vaccine-induced immunity in individuals with high pre-existing influenza immunity._ Frontiers in Immunology, 2025. DOI: 10.3389/fimmu.2025.1663763. PMID: 41208956. - **Ginzac 2025.** _Melatonin supplementation for quality of life in older patients with advanced cancer: a randomized controlled trial._ BMC Geriatrics, 2025. DOI: 10.1186/s12877-025-06899-1. PMID: 41421991. - **Sadeghpour 2025.** _The effects of melatonin on follicular oxidative stress and art outcomes in women with diminished ovarian reserve: a randomized controlled trial._ Journal of Ovarian Research, 2025. DOI: 10.1186/s13048-024-01584-0. PMID: 39780224. - **Saraiva 2026.** _Low‐Dose Melatonin, Climacteric Symptoms and Sleep in Female Shift Workers: A Randomized Controlled Trial._ Journal of Pineal Research, 2026. DOI: 10.1111/jpi.70140. PMID: 41841489. - **AL-agooz 2025.** _Clinical and radiographic evaluation of melatonin and chitosan loaded nanoparticles in the treatment of periodontal intra-bony defects: A Randomized controlled clinical trial._ Clinical Oral Investigations, 2025. DOI: 10.1007/s00784-025-06323-3. PMID: 40312586. - **Suram 2025.** _Dysregulation of melatonin rhythm in Parkinson’s and Huntington’s disease: a systematic review and meta-analysis._ Frontiers in Aging Neuroscience, 2025. DOI: 10.3389/fnagi.2025.1637881. PMID: 41143249. - **Alghamdi 2026.** _Effectiveness of melatonin supplementation for improving sleep quality and disease severity in children with atopic dermatitis: a systematic review and meta-analysis._ Frontiers in Medicine, 2026. DOI: 10.3389/fmed.2025.1718859. PMID: 41647028. - **Bradfield 2025.** _Double-blind, randomised, placebo-controlled trial to evaluate the effectiveness of late gestation oral melatonin supplementation in reducing induction of labour rates in nulliparous women: the MyTIME study protocol._ BMJ Open, 2025. DOI: 10.1136/bmjopen-2024-090370. PMID: 39855663. - **Haq 2025.** _Melatonin for blood pressure control in adults._ The Cochrane Database of Systematic Reviews, 2025. DOI: 10.1002/14651858.CD016159. PMID: 40955729. - **Queiroz 2025.** _Effect of peri‐operative pharmacological interventions on postoperative delirium in patients having cardiac surgery: a systematic review and Bayesian network meta‐analysis._ Anaesthesia, 2025. DOI: 10.1111/anae.16757. PMID: 40888048. - **Akhavan 2026.** _Comparing Intranasal Midazolam, Oral Melatonin, and Distraction Cards for Pain and Stress Management in Pediatric Intravenous Line Insertion: A Randomized Controlled Trial._ Pain Research & Management, 2026. DOI: 10.1155/prm/9887917. PMID: 41696535. - **Gupta 2025.** _Relative Efficacy of Conventional Monotherapies and Select Nonconventional, Over‐the‐Counter Products for Male Androgenetic Alopecia: A Network Meta‐Analysis Study._ Journal of Cosmetic Dermatology, 2025. DOI: 10.1111/jocd.70483. PMID: 41051009. - **Esmaeilzadeh 2025.** _Melatonin and sleep parameters in infertile women with endometriosis: first results from the triple-blind randomized controlled trial of administration of melatonin in chronic pelvic pain and sleep disturbance._ PLOS One, 2025. DOI: 10.1371/journal.pone.0321635. PMID: 40238733. - **Lv 2025.** _The effect of melatonin supplementation on glycemic control in patients with type 2 diabetes._ Frontiers in Endocrinology, 2025. DOI: 10.3389/fendo.2025.1572613. PMID: 40698248. - **Nofal 2026.** _Melatonin effects on the left ventricular function in neonates with persistent pulmonary hypertension._ European Journal of Pediatrics, 2026. DOI: 10.1007/s00431-026-06864-z. PMID: 41954764. - **Kilic 2025.** _Melatonin for chronic back pain (the MOCHA trial): study protocol for a randomized, double-blind, placebo-controlled trial._ Trials, 2025. DOI: 10.1186/s13063-025-09206-w. 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"title": "Research Synthesis: Melatonin Aging \u2014 full paper"
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