Derivation Web

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by researka:v2 · 2026-06-15 20:02:07.778639+04:00

{"publication_id": "2e53f7ae-1495-4dbd-b9ef-742ac8ba8353", "traces": [{"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "This paper synthesizes evidence on resveratrol metabolism effects across 33 accepted source papers and 900 high-confidence extracted claims.", "claim_id": "claim_1"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "The evidence profile contains 2 direct clinical sources, 17 adjacent clinical sources, and 9 mechanistic or model-system sources, with 86 cross-study disagreements across the evidence base.", "claim_id": "claim_2"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "Positive study-level signals are summarized in the cardiometabolic outcome class, null signals in the contextual adjacent evidence, skeletal, fracture, and bone, dosing and pharmacokinetics outcome classes, and negative signals in the contextual adjacent evidence outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "claim_id": "claim_3"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "The conclusion is that resveratrol metabolism effects remains a bounded geroscience case: the retained clinical and mechanistic evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.", "claim_id": "claim_4"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint.", "claim_id": "claim_5"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "Population aging has become the defining demographic transition of the twenty-first century, and with it the central clinical question has shifted from managing individual diseases diagnosed in late life to extending the period of life spent in good function, a construct often termed healthspan. The question of whether pharmacologic interventions can lengthen healthspan, and indirectly lifespan, has moved from speculative biology into the center of translational research agendas, and it is being asked with renewed urgency because the social and economic costs of multimorbidity, frailty, and disability are rising faster than curative pipelines can offset them. In this context, the candidate compound Resveratrol Metabolism Effects has been repeatedly invoked, because it is one of a small number of molecules for which mechanistic data, observational clues, and a substantial body of human trial evidence already coexist. It is precisely the coexistence of those layers, rather than the strength of any one of them, that makes the Resveratrol Metabolism Effects case a useful test case for the geroscience hypothesis, and the field's enthusiasm for the drug has grown alongside, not ahead of, the published evidence base. The clinical stakes are concrete: skeletal fragility, metabolic dysfunction, and inflammatory drift all cluster at the interface between aging and chronic disease, and an intervention that meaningfully modulated any one of them would have immediate public-health implications. The challenge is that 'meaningful modulation' remains the open question, and the published record on Resveratrol Metabolism Effects, taken as a whole, has not yet converged on a defensible yes-or-no answer.", "claim_id": "claim_6"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "The geroscience hypothesis proposes that aging biology itself is a tractable therapeutic target, and that interventions which slow fundamental aging processes should, in principle, delay or compress the morbidity curve across multiple organ systems simultaneously. This contrasts with the traditional single-disease, single-target model of drug development, and it has generated interest in both novel molecules and the repurposing of existing compounds with favorable safety profiles. The repurposing pathway is attractive because the cost and timeline of de novo development are prohibitive for a prevention indication that would require very long follow-up, and the regulatory bar for chronic, healthy-adult use is unusually high. Within this logic, Resveratrol Metabolism Effects has occupied a peculiar position: it is widely available as a supplement, has a long informal safety record, and yet is being asked to meet an evidentiary standard that no geroprotector has yet met. The geroscience framework does not, in itself, predict that Resveratrol Metabolism Effects will work; it predicts that if a compound does slow aging biology, the signal should be detectable in coordinated changes across cardiometabolic, skeletal, inflammatory, and possibly cognitive endpoints. The empirical record on Resveratrol Metabolism Effects can therefore be evaluated against the geroscience expectation of multi-domain coordination, and the question of whether such coordination is in fact observed is one of the organizing questions of the present synthesis. Importantly, the hypothesis also tolerates null findings on individual outcomes, provided the pattern across outcomes is interpretable, and that tolerance makes the evaluation of Resveratrol Metabolism Effects a methodological exercise as much as a biological one.", "claim_id": "claim_7"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "Several unresolved questions run through the Resveratrol Metabolism Effects evidence base, and they are not all answerable with the same kind of study. The first is the mechanism-to-function translation problem: there is no shortage of plausible molecular targets for Resveratrol Metabolism Effects, but the question of which, if any, is operative at achievable human exposures remains open, and the gap between in-vitro concentrations used to demonstrate target engagement and plasma concentrations observed in vivo is consistently large. The second is the tradeoff question: even where a small positive signal is observed, whether it is large enough to be clinically meaningful, given the typical attrition rate in long-duration RCTs of older adults of roughly 20% (Schulz 2010), is not settled. The third is population specificity, and there is suggestive evidence that baseline metabolic status, sex, and gut microbiota composition may modify the response, but the trials currently available are not adequately powered to resolve these interactions. The fourth is duration: geroscience-style endpoints require follow-up on the order of years, while most Resveratrol Metabolism Effects trials run for 12 weeks, and the longer-term safety and efficacy profile in healthy adults is therefore under-characterized. The fifth is dose-response: the Limin 2026 transcriptomic-metabolomic work in arctic foxes and other pharmacokinetic analyses have raised the possibility of a non-monotonic dose-effect relationship, which complicates simple linear interpretations. These questions are interlocked, and the present synthesis is structured to keep them visible rather than to collapse them into a single answer.", "claim_id": "claim_8"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "The biological rationale is treated as context rather than as clinical proof. Population fit, comparator alignment, clinical directness, follow-up length, ascertainment method, baseline risk, adherence, exposure dose, and external validity are kept separate during interpretation. The interpretation", "claim_id": "claim_9"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "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.", "claim_id": "claim_10"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "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`.", "claim_id": "claim_11"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, dosing and pharmacokinetics, immune, immune and inflammation, skeletal, fracture, and bone); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.", "claim_id": "claim_12"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "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.", "claim_id": "claim_13"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "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.", "claim_id": "claim_14"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "claim_id": "claim_15"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "| Contextual Adjacent Evidence | n=25; claims=493 | no extracted directional signal in 24/25 sources | 15 indirect; 7 mechanistic; 3 review | limited corpus depth in this outcome class |", "claim_id": "claim_16"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "Contextual Adjacent Evidence: n=25; claims=493; no extracted directional signal in 24/25 sources | directness: 15 indirect; 7 mechanistic; 3 review; main limitation: no direct clinical anchor.", "claim_id": "claim_17"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "The cardiometabolic outcome class is anchored by one clinical RCT and one systematic review, both of which examined glucose and lipid endpoints under resveratrol supplementation. Chen 2015 was a randomized controlled trial in adults with non-alcoholic fatty liver disease, with resveratrol supplementation compared with placebo (P≤0.001, P = 0.002, and P = 0.016 respectively, Chen 2015). Detailed per-endpoint study × p-value tuples are presented in the evidence synthesis, which should be read alongside the prose summary below. The source-traced numerics support a positive direction of effect for both pieces of evidence.", "claim_id": "claim_18"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "detect favourable shifts in glycaemic and lipid markers rather than deterioration. No source in this outcome class reported a null or negative effect, and the cardiometabolic class is the signal in the corpus.", "claim_id": "claim_19"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "Mechanistically, the cardiometabolic findings can be linked to resveratrol's documented activity on hepatic lipid handling and insulin signalling, substrates most directly probed by Chen 2015 in a clinical RCT population. Preclinical data elsewhere in the broader literature have proposed sirtuin-1 and AMPK-mediated pathways as the molecular substrate, but the present corpus provides only the clinical-RCT and pooled-review layer for this outcome class. Chen 2015 is a direct clinical functional-endpoint trial, whereas Zhou 2022 is a review-level synthesis, so the mechanistic interpretation rests on Chen 2015's within-trial biochemistry and on the pattern of pooled estimates reported in Zhou 2022. This stratification of direct versus review-level evidence is essential when assessing transferability of the cardiometabolic signal to other populations.", "claim_id": "claim_20"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "Within-corpus tensions for the cardiometabolic class are limited but non-trivial: Chen 2015 and Zhou 2022 agree on direction, but they differ in evidence type — Chen 2015 is a direct clinical RCT in adults, while Zhou 2022 is an indirect review-level synthesis without its own enrolled clinical population. This direct-versus-indirect asymmetry is recorded in the cross-study disagreement map as an indirectness gap (severity 3) for the cardiometabolic outcome class. Practically, the gap means that the magnitude estimates in Zhou 2022 cannot be assumed to track Chen 2015's within-trial effect sizes one-to-one, even though both report favourable p-values. Until further direct trials converge on the same endpoints, the cardiometabolic claim can be interpreted as supported by concordant direct and indirect evidence rather than as a single replicated effect.", "claim_id": "claim_21"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "The contextual outcome class aggregates the heterogeneous metabolic, pharmacokinetic, formulation, and tissue-level evidence base surrounding resveratrol, populated almost entirely by indirect, mechanistic, or review-level studies. Together, these framing studies delineate the broad translational surface across which the downstream mechanistic and clinical findings must be interpreted.", "claim_id": "claim_22"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "Within Limin 2026, the directional pattern is non-monotonic: at the 50 mg/kg dose testosterone output was enhanced, while departures from that dose in either direction were associated with attenuated or null effects captured by the P > 0.05 contrasts. The source reports six significance statements, with two P < 0.05 and two P < 0.01 contrasts anchoring the optimal-dose response and two P > 0.05 contrasts flagging sub-optimal and supra-optimal doses. Because Limin 2026 is an animal observational cohort, no human pharmacokinetic parameters — bioavailability, half-life, or area-under-the-curve — are derived; readers should treat the dose label as a within-study experimental anchor rather than a translatable human regimen.", "claim_id": "claim_23"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "Mechanistically, the non-monotonic profile is consistent with hormetic biology, in which low-dose receptor engagement (sirtuin and AMPK-pathway activation) gives way to off-target or feedback inhibition at higher exposures, and the integrated transcriptomic-metabolomic design in Limin 2026 is positioned to detect such inflection points. The source does not enumerate specific human-RCT pharmacokinetic thresholds such as canonical bioavailability ranges; consequently, the mechanistic narrative here is anchored to the animal-model transcriptomic-metabolomic evidence rather than to any clinical pharmacokinetic reference. The directness tag (indirect) reinforces that the receptor-pathway inference is carried rather than measured directly in humans.", "claim_id": "claim_24"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "In animal/preclinical evidence, within-corpus tensions on this outcome class are limited because Limin 2026 is the only curated source for dosing pharmacokinetics, and the cross-study disagreement map records no same-outcome non-orthogonal pairs to surface disagreements. Consequently, the dose-response narrative rests on a single observational cohort, and the absence of an opposing source precludes any contrast in directional effect. The integrating thesis for Resveratrol Metabolism Effects is consistent with this limitation: the evidence base is acknowledged as incomplete, with mechanistic plausibility coexisting with sparse human-RCT data, and the boundary conditions for an optimal dose remain to be established in human populations. Readers should treat the 50 mg/kg anchor as a hypothesis-generating dose in Vulpes lagopus, not a clinically translatable regimen, pending dedicated human pharmacokinetic studies.", "claim_id": "claim_25"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "The immune outcome class in the resveratrol metabolism evidence base is anchored by a single preclinical investigation evaluating hepatotoxicity mitigation, leaving the human-RCT complement for this domain sparse. Sobh 2026 examined the mechanistic actions of resveratrol-loaded chitosan nanoparticles against chlorfenapyr-induced liver injury, embedding immune endpoints within a broader panel that included liver function, lipid profile, oxidative stress markers, antioxidant defense system, energy metabolism, mitochondrial function, and inflammatory gene expression. The endpoint architecture is therefore multi-organ and pathway-rich, with inflammatory gene readouts positioned as one of several mechanistic strata rather than as a primary isolated outcome. Dose, duration, and animal-model parameters are reported within the source as P < 0.05 supporting entries without further granularity in the indexed excerpt.", "claim_id": "claim_26"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "Mechanistically, the Sobh 2026 study reports statistically supported changes (P < 0.05) across the integrated liver–metabolism–inflammation panel, indicating that the resveratrol-loaded nanoparticle formulation altered inflammatory gene expression in the context of toxicant challenge. The directness tag is mechanistic, so the findings establish biological plausibility for an immunomodulatory action of resveratrol delivered via a chitosan nanocarrier rather than a confirmatory clinical effect. Effect sizes, confidence intervals, and exact sample sizes are not exposed in the indexed excerpt, so the quantitative contour of the P < 0.05 signal cannot be re-expressed here. Readers are referred to the evidence synthesis (Per-Study Endpoint Evidence) for the full per-endpoint p-value inventory as carried by the source.", "claim_id": "claim_27"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "Mechanistically, the inflammatory-gene signal in Sobh 2026 sits downstream of the same oxidative-stress and mitochondrial-function readouts that also carry P < 0.05 support, consistent with a coupled redox–inflammation axis in the chlorfenapyr-injury model. This positions resveratrol-loaded chitosan nanoparticles as a delivery-format-specific intervention whose immune effect is plausibly mediated through antioxidant defense restoration and improved mitochondrial function rather than through direct cytokine suppression. Because the directness is mechanistic and the population is adults only in the source descriptor, translation to clinical immune endpoints in human aging remains an extrapolation. The mechanistic substrate underlying this functional finding therefore remains preclinical in evidentiary status.", "claim_id": "claim_28"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "Within-corpus tensions in the immune outcome class cannot be enumerated from the cross-study disagreement map, which contains no same-outcome non-orthogonal pairs for immune endpoints; the class is therefore single-source and does not surface internal disagreement. The direction tag for Sobh 2026 is recorded as unclear, so even the valence of the mechanistic immune effect is not adjudicated in the corpus. Practically, this means the immune outcome class contributes mechanistic plausibility — inflammatory gene expression changes with P < 0.05 support in a toxicant-challenge preclinical model — without a parallel human-RCT confirmation in the indexed set. The trial plans to enroll 472 elderly patients with type 2 diabetes mellitus and is positioned as a randomized controlled clinical trial protocol. The reported study is therefore protocol-level rather than completed results, and the direction of effect is recorded as unclear in the curated evidence. The protocol explicitly bundles glucose metabolism, insulin resistance, inflammation, and renal function as co-primary endpoints, situating inflammation within a broader cardiometabolic-renal cluster rather than as a stand-alone outcome.", "claim_id": "claim_29"}, {"candidate_sources": [{"doi": "10.4062/biomolther.2025.018", "study": "trans -Resveratrol and Hesperidin Supplementation with Treadmill Exercise Alleviates Methylglyoxal-Induced Skeletal Muscle Dysfunction", "url": "https://doi.org/10.4062/biomolther.2025.018"}, {"doi": "10.1016/j.vas.2026.100666", "study": "The non-monotonic dose-effect of resveratrol on testicular steroidogenesis in male arctic foxes (Vulpes lagopus): Mechanisms revealed by integrated transcriptomic and metabolomic analyses", "url": "https://doi.org/10.1016/j.vas.2026.100666"}, {"doi": "10.3389/fphys.2022.795980", "study": "Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic Review", "url": "https://doi.org/10.3389/fphys.2022.795980"}, {"doi": "10.3390/ani16111574", "study": "Resveratrol Alleviates Corticosterone-Induced Hepatic Lipid Metabolism Disorder and Oxidative Stress by Regulating the Nrf2 and AMPK/Sirt1 Signaling Pathways in AA Broilers", "url": "https://doi.org/10.3390/ani16111574"}, {"doi": "10.1080/19490976.2024.2392875", "study": "Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity", "url": "https://doi.org/10.1080/19490976.2024.2392875"}], "claim": "The source reports only threshold-style p-values rather than completed effect estimates, listing P < 0.05 and P < 0.01 as anticipated statistical benchmarks across the bundled endpoints. Because the trial is a protocol, no point estimates, confidence intervals, or hazard ratios are available in the source, and the precise allocation of P < 0.05 versus P < 0.01 to the inflammation endpoint versus the metabolic or renal endpoints cannot be resolved from the curated excerpt. The absence of completed results means that immune inflammation evidence in this corpus is presently a forward-looking signal rather than a quantified finding. Quantitative interpretation is therefore deferred until the trial reports outcomes.", "claim_id": "claim_30"}]}

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