Derivation Web

source_308c82edc13b45b8

by researka:v2 · 2026-06-24 04:42:41.431128+04:00

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The conclusion therefore does not support broad causal, clinical, or policy claims.", "type": "claim"}, {"id": "claim_2", "text": "This synthesis tests the thesis that evidence for NAD+ Effects is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation.", "type": "claim"}, {"id": "claim_3", "text": "Nicotinamide adenine dinucleotide (NAD+) replenishment has attracted substantial interest as a candidate intervention for age-related functional decline, yet the human evidence base remains fragmented across precursor formulations, populations, and endpoint categories.", "type": "claim"}, {"id": "claim_4", "text": "This synthesis was assembled through an AI-assisted structured evidence review in which each candidate paper was classified by study design, outcome domain, and directness tier before being retained or downgraded, with an explicit audit trail linking every claim to a source.", "type": "claim"}, {"id": "claim_5", "text": "Across the corpus, the sources support the conclusion that oral NAD+-precursor supplementation consistently elevates circulating NAD+ in middle-aged and older adults but delivers context-dependent functional effects: isolated organ-specific successes (e. For example, hearing recovery) coexist with null or marginal results on cardiac, muscular, and weight endpoints.", "type": "claim"}, {"id": "claim_6", "text": "Evidence-abstraction note.** The 30 retained reference papers are not 30 independent primary clinical trials: 25 are review, indirect, mechanistic, or registered-protocol source-level summaries, and 5 are classified as direct interventional evidence. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence.", "type": "claim"}, {"id": "claim_7", "text": "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-nad_effects-v06-DAILY-2026-06-24T00-20-28Z-R2`.", "type": "claim"}, {"id": "claim_8", "text": "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 sidecar when populated, and claim registry) rather than from re-parsed full text.", "type": "claim"}, {"id": "claim_9", "text": "Risk-of-bias framework assignment follows study design (RoB-2 for RCTs, ROBINS-I for non-randomised studies, AMSTAR-2 for systematic reviews / meta-analyses). Public appraisal claims are limited to populated `risk_of_bias.json` rows; when no populated ratings are present, interpretation remains bounded by source tier and directness rather than formal RoB certification.", "type": "claim"}, {"id": "claim_10", "text": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, dosing and pharmacokinetics, frailty, immune and inflammation, longevity, muscle function, 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.", "type": "claim"}, {"id": "claim_11", "text": "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.", "type": "claim"}, {"id": "claim_12", "text": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "type": "claim"}, {"id": "claim_13", "text": "| Contextual Adjacent Evidence | n=16; claims=915 | no extracted directional signal in 8/16 sources | 3 direct; 12 indirect; 1 review | limited corpus depth in this outcome class |", "type": "claim"}, {"id": "claim_14", "text": "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.", "type": "claim"}, {"id": "claim_15", "text": "This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.", "type": "claim"}, {"id": "claim_16", "text": "16 included sources were assigned to this outcome class. Directional coding: negative=2, null=8, positive=1, unclear=5. Directness coding: direct=3, indirect=12, review=1.", "type": "claim"}, {"id": "claim_17", "text": "Evidence for this outcome class is represented in the structured results table, but the retained narrative paragraphs were more strongly assigned to adjacent outcome classes. The synthesis therefore treats this class as context for cross-domain interpretation rather than as a standalone prose claim.", "type": "claim"}, {"id": "claim_18", "text": "1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: mechanistic=1.", "type": "claim"}, {"id": "claim_19", "text": "1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.", "type": "claim"}, {"id": "claim_20", "text": "Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.", "type": "claim"}, {"id": "claim_21", "text": "The curated corpus for NAD+ carries a foundational gap in long-horizon clinical evidence.", "type": "claim"}, {"id": "claim_22", "text": "Additional corpus sources included animal/preclinical evidence; the endpoint inventory is dominated by pharmacodynamic and biomarker readouts rather than functional or hard clinical outcomes. Most sources measure blood or tissue NAD+ levels, NAD+/NADH ratio (Ren 2023: brain target engagement in Parkinson's and multiple sclerosis), or short-term performance surrogates (Liao 2021: amateur runners, 300/600/1200 mg/day NMN; Liao 2021 reports aerobic-capacity endpoints but with no mortality follow-up). Gait speed — a domain where canonical thresholds exist (0.8 m/s, Studenski 2011; 0.6 m/s, Cesari 2009; a 0.1 m/s change is considered clinically meaningful, Perera 2006) — is not directly measured in any source, so mobility-based interpretation must be inferred from upstream molecular signals. Adverse-event collection is also short and inconsistent: Curran 2023 (CKD context) flags that chronic kidney disease affects more than 10% of the global population but provides no human supplementation safety synthesis, and chronic-dosing safety beyond weeks cannot be established from this corpus.", "type": "claim"}, {"id": "claim_23", "text": "The corpus contains genuine mechanistic and cross-species evidence that does not translate directly to clinical claims. Curran 2025 is a meta-analysis of niacin and NAD-metabolite treatment in infectious-disease animal studies, not in humans, and its positive directional signal (effect direction: positive) cannot be aggregated with human RCT effect sizes. As a methodological matter, surrogate associations do not guarantee hard-outcome validity (Ioannidis 2005), and the most defensible reading of the corpus is that the mechanistic-to-clinical bridge remains incomplete for skeletal-muscle, infectious-disease, and frailty indications until adequately powered human trials with functional endpoints are available.", "type": "claim"}, {"id": "claim_24", "text": "For NAD+ effects, the final interpretation is deliberately tiered: the retained clinical and mechanistic 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 interventional hard-endpoint 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 NAD+ effects 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.", "type": "claim"}, {"id": "claim_25", "text": "This synthesis maps 30 included sources on NAD+ Effects across 8 outcome classes and 146 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.", "type": "claim"}, {"id": "claim_26", "text": "Across 30 curated reference papers, the evidence base for NAD+ shows a context-dependent profile. Positive signals appear in: frailty. Negative signals appear in: contextual other, longevity. Null findings dominate: contextual other, dosing pharmacokinetics. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The NAD+ 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.", "type": "claim"}, {"id": "claim_27", "text": "The strongest unresolved contrast is the disagreement between Zhao 2024 and Curran 2025 on contextual adjacent evidence (severity 5/5), which defines the boundary condition future studies must test rather than smooth over.", "type": "claim"}, {"id": "claim_28", "text": "Prior reviews in the corpus (Curran 2025, Baichuan 2023, Han 2022) emphasize convergent signals on NAD+ Effects. 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.", "type": "claim"}, {"id": "claim_29", "text": "| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |", "type": "claim"}, {"id": "claim_30", "text": "| cardiometabolic | 0 | 3 | mixed, null, unclear | direct interventional hard-endpoint gap |", "type": "claim"}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41598-023-29787-3", "effect": "not extracted", "endpoint": "not extracted", "id": "source_1", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "type": "source", "url": "https://doi.org/10.1038/s41598-023-29787-3", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1093/jn/nxab193", "effect": "not extracted", "endpoint": "not extracted", "id": "source_2", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "NAD + -Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults", "type": "source", "url": "https://doi.org/10.1093/jn/nxab193", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1002/lary.70173", "effect": "not extracted", "endpoint": "not extracted", "id": "source_3", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "NAD+ Enhanced on Hearing Recovery in Sudden Sensorineural Hearing Loss: Randomized Controlled Trial", "type": "source", "url": "https://doi.org/10.1002/lary.70173", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41467-024-53292-4", "effect": "not extracted", "endpoint": "not extracted", "id": "source_4", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "type": "source", "url": "https://doi.org/10.1038/s41467-024-53292-4", "year": 2024}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1038/s41598-025-95735-y", "effect": "not extracted", "endpoint": "not extracted", "id": "source_5", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "type": "source", "url": "https://doi.org/10.1038/s41598-025-95735-y", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s11357-022-00705-1", "effect": "not extracted", "endpoint": "not extracted", "id": "source_6", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial", "type": "source", "url": "https://doi.org/10.1007/s11357-022-00705-1", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41598-024-63031-w", "effect": "not extracted", "endpoint": "not extracted", "id": "source_7", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD+ precursor combination", "type": "source", "url": "https://doi.org/10.1038/s41598-024-63031-w", "year": 2024}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1186/s12882-020-02006-1", "effect": "not extracted", "endpoint": "not extracted", "id": "source_8", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Nicotinamide riboside with pterostilbene (NRPT) increases NAD + in patients with acute kidney injury (AKI): a randomized, double-blind, placebo-controlled, stepwise safety study of escalating doses of NRPT in patients with AKI", "type": "source", "url": "https://doi.org/10.1186/s12882-020-02006-1", "year": 2020}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fnut.2022.868640", "effect": "not extracted", "endpoint": "not extracted", "id": "source_9", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects", "type": "source", "url": "https://doi.org/10.3389/fnut.2022.868640", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/nu14112219", "effect": "not extracted", "endpoint": "not extracted", "id": "source_10", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "A Combination of Nicotinamide and D-Ribose (RiaGev) Is Safe and Effective to Increase NAD + Metabolome in Healthy Middle-Aged Adults: A Randomized, Triple-Blind, Placebo-Controlled, Cross-Over Pilot Clinical Trial", "type": "source", "url": "https://doi.org/10.3390/nu14112219", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1111/apt.70302", "effect": "not extracted", "endpoint": "not extracted", "id": "source_11", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Refining Prognosis in Cirrhosis Patients With Ascites: Impact of Acute vs. Non‐Acute Decompensation", "type": "source", "url": "https://doi.org/10.1111/apt.70302", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12951-023-02236-z", "effect": "not extracted", "endpoint": "not extracted", "id": "source_12", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Evidence of brain target engagement in Parkinson’s disease and multiple sclerosis by the investigational nanomedicine, CNM-Au8, in the REPAIR phase 2 clinical trials", "type": "source", "url": "https://doi.org/10.1186/s12951-023-02236-z", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.2147/NDT.S446034", "effect": "not extracted", "endpoint": "not extracted", "id": "source_13", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Acupuncture as Add-on Therapy to SSRIs Can Improve Outcomes of Treatment for Anxious Depression: Subgroup Analysis of the AcuSDep Trial", "type": "source", "url": "https://doi.org/10.2147/NDT.S446034", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s40256-025-00764-7", "effect": "not extracted", "endpoint": "not extracted", "id": "source_14", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effect of Nicotinamide Adenine Dinucleotide on Heart Failure Caused by Ischemic Cardiomyopathy: A Randomized, Placebo-Controlled Trial", "type": "source", "url": "https://doi.org/10.1007/s40256-025-00764-7", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.31083/j.rcm2508297", "effect": "not extracted", "endpoint": "not extracted", "id": "source_15", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effects of Nicotinamide Adenine Dinucleotide on Older Patients with Heart Failure", "type": "source", "url": "https://doi.org/10.31083/j.rcm2508297", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12894-022-01107-3", "effect": "not extracted", "endpoint": "not extracted", "id": "source_16", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Relationship between sperm NAD + concentration and reproductive aging in normozoospermia men:A Cohort study", "type": "source", "url": "https://doi.org/10.1186/s12894-022-01107-3", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12967-023-04584-8", "effect": "not extracted", "endpoint": "not extracted", "id": "source_17", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The complexity of nicotinamide adenine dinucleotide (NAD), hypoxic, and aryl hydrocarbon receptor cell signaling in chronic kidney disease", "type": "source", "url": "https://doi.org/10.1186/s12967-023-04584-8", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12970-021-00442-4", "effect": "not extracted", "endpoint": "not extracted", "id": "source_18", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study", "type": "source", "url": "https://doi.org/10.1186/s12970-021-00442-4", "year": 2021}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.3389/fnut.2023.1208734", "effect": "not extracted", "endpoint": "not extracted", "id": "source_19", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The effects of NAD+ precursor (nicotinic acid and nicotinamide) supplementation on weight loss and related hormones: a systematic review and meta-regression analysis of randomized controlled trials", "type": "source", "url": "https://doi.org/10.3389/fnut.2023.1208734", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/cimb47090722", "effect": "not extracted", "endpoint": "not extracted", "id": "source_20", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "A Liposomal Formulation Enhances the Anti-Senescence Properties of Nicotinamide Adenine-Dinucleotide (NAD + ) in Endothelial Cells and Keratinocytes", "type": "source", "url": "https://doi.org/10.3390/cimb47090722", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fragi.2026.1773667", "effect": "not extracted", "endpoint": "not extracted", "id": "source_21", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Nicotinamide riboside and pterostilbene reduces frequency and severity of undesirable symptoms of the menopause transition: an open-label, pilot clinical trial", "type": "source", "url": "https://doi.org/10.3389/fragi.2026.1773667", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s42255-025-01421-8", "effect": "not extracted", "endpoint": "not extracted", "id": "source_22", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The differential impact of three different NAD + boosters on circulatory NAD and microbial metabolism in humans", "type": "source", "url": "https://doi.org/10.1038/s42255-025-01421-8", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s42255-024-00997-x", "effect": "not extracted", "endpoint": "not extracted", "id": "source_23", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Trigonelline is an NAD + precursor that improves muscle function during ageing and is reduced in human sarcopenia", "type": "source", "url": "https://doi.org/10.1038/s42255-024-00997-x", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.22038/IJBMS.2022.65117.14335", "effect": "not extracted", "endpoint": "not extracted", "id": "source_24", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Ameliorating effect of 6-week swimming exercise on mice with experimental autoimmune encephalomyelitis (EAE) by reducing fetuin-A and increasing AMPK & NAD ⁺ levels in liver tissue", "type": "source", "url": "https://doi.org/10.22038/IJBMS.2022.65117.14335", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1016/j.redox.2026.104146", "effect": "not extracted", "endpoint": "not extracted", "id": "source_25", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "SERPINE1 drives ferroptosis in acute respiratory distress syndrome by disrupting mitochondrial NAD + homeostasis and suppressing Sirt3 activity", "type": "source", "url": "https://doi.org/10.1016/j.redox.2026.104146", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1016/j.chemosphere.2021.132893", "effect": "not extracted", "endpoint": "not extracted", "id": "source_26", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The impacts of continuous improvements in air quality on mortality in Beijing: A longitudinal comparative study.", "type": "source", "url": "https://doi.org/10.1016/j.chemosphere.2021.132893", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1111/acel.13754", "effect": "not extracted", "endpoint": "not extracted", "id": "source_27", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin", "type": "source", "url": "https://doi.org/10.1111/acel.13754", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41467-018-03421-7", "effect": "not extracted", "endpoint": "not extracted", "id": "source_28", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD + in healthy middle-aged and older adults", "type": "source", "url": "https://doi.org/10.1038/s41467-018-03421-7", "year": 2018}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1371/journal.pone.0186459", "effect": "not extracted", "endpoint": "not extracted", "id": "source_29", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers", "type": "source", "url": "https://doi.org/10.1371/journal.pone.0186459", "year": 2017}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1016/j.celrep.2019.07.043", "effect": "not extracted", "endpoint": "not extracted", "id": "source_30", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD + Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures", "type": "source", "url": "https://doi.org/10.1016/j.celrep.2019.07.043", "year": 2019}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_31", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_32", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Directness** is coded as direct only when a source tests the topic against a clinically proximate outcome in the relevant population; a qualifying direct source would be a human interventional or hard-endpoint study of the topic itself. Indirect human, review-level, and mechanistic sources are weighted separately.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_33", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Directional signal** is counted within the assigned outcome class only. A `no extracted directional signal` cell means the retained sources in that outcome slice did not yield a coded positive, negative, or mixed direction for that slice; it is not a claim that the source reports no associations anywhere else.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_34", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Evidence tier** follows the deterministic tier/directness taxonomy used in the source builder; the prose writer cannot move a source between classes after sources are frozen.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1001/jama.2010.1923", "effect": "not extracted", "endpoint": "not extracted", "id": "source_35", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Studenski 2011", "type": "source", "url": "https://doi.org/10.1001/jama.2010.1923", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1093/gerona/glp012", "effect": "not extracted", "endpoint": "not extracted", "id": "source_36", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Cesari 2009", "type": "source", "url": "https://doi.org/10.1093/gerona/glp012", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1111/j.1532-5415.2006.00701.x", "effect": "not extracted", "endpoint": "not extracted", "id": "source_37", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Perera 2006", "type": "source", "url": "https://doi.org/10.1111/j.1532-5415.2006.00701.x", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1371/journal.pmed.0020124", "effect": "not extracted", "endpoint": "not extracted", "id": "source_38", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Ioannidis 2005", "type": "source", "url": "https://doi.org/10.1371/journal.pmed.0020124", "year": null}], "publication_id": "941512c2-b114-4c13-986c-205ddb9531a5", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", "included"], "identified": 30, "included": 30, "included_or_retained": 30, "screened": 30, "wording": "30 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit."}}

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