{"publication_id":"ca403171-b282-4695-8058-9dd6bfe3754b","content_hash":"sha256:dd803f123cfa1795c54a705ddba5eccb54291a90f143a2b28752cd00f07b942b","nodes":[{"id":"ca403171-b282-4695-8058-9dd6bfe3754b","type":"publication","title":"Research Synthesis: Nad Effects — full paper"},{"id":"claim_1","type":"claim","text":"Evidence-honesty note: 15/29 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. 27/29 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims."},{"id":"claim_2","type":"claim","text":"The evidence profile contains 2 direct clinical sources, 20 adjacent clinical sources, and 2 mechanistic or model-system sources, with 98 cross-study disagreements across the evidence base."},{"id":"claim_3","type":"claim","text":"Positive study-level signals are summarized in the contextual adjacent evidence, immune and inflammation outcome classes, null signals in the contextual adjacent evidence, cardiometabolic, dosing and pharmacokinetics outcome classes, and negative signals in the longevity and contextual adjacent evidence outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect."},{"id":"claim_4","type":"claim","text":"The conclusion is that nad effects should be treated as a bounded geroscience hypothesis: the retained clinical and mechanistic evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim."},{"id":"claim_5","type":"claim","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-2026-06-07T05-02-41Z-R3`."},{"id":"claim_6","type":"claim","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 appraisal, and claim registry) rather than from re-parsed full text."},{"id":"claim_7","type":"claim","text":"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`."},{"id":"claim_8","type":"claim","text":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, dosing and pharmacokinetics, frailty, immune and inflammation, longevity, safety and comorbidity, 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."},{"id":"claim_9","type":"claim","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."},{"id":"claim_10","type":"claim","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."},{"id":"claim_11","type":"claim","text":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |"},{"id":"claim_12","type":"claim","text":"| Contextual Adjacent Evidence | n=13; claims=636 | no extracted directional signal in 9/13 sources | 1 direct; 9 indirect; 1 mechanistic; 2 review | limited corpus depth in this outcome class |"},{"id":"claim_13","type":"claim","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."},{"id":"claim_14","type":"claim","text":"13 included sources were assigned to this outcome class. Directional coding: negative=1, null=9, positive=1, unclear=2. Directness coding: direct=1, indirect=9, mechanistic=1, review=2."},{"id":"claim_15","type":"claim","text":"6 included sources were assigned to this outcome class. Directional coding: null=3, unclear=3. Directness coding: indirect=5, review=1."},{"id":"claim_16","type":"claim","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."},{"id":"claim_17","type":"claim","text":"1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1."},{"id":"claim_18","type":"claim","text":"1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1."},{"id":"claim_19","type":"claim","text":"Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim."},{"id":"claim_20","type":"claim","text":"The curated corpus is dominated by small, short-duration, mechanistic-biomarker trials rather than large, long-term randomized controlled trials powered for hard clinical endpoints such as mortality, cardiovascular events, or incident frailty. No long-term mortality trial in this corpus provides direct evidence that NAD precursor supplementation prolongs life. Consequently, the headline conclusion that NAD precursors exert clinically meaningful anti-aging effects rests almost entirely on surrogate markers rather than validated hard outcomes (Ioannidis 2005), creating a substantial gap between mechanistic promise and patient-centered proof."},{"id":"claim_21","type":"claim","text":"Several outcome domains within the evidence base are each represented by only a single human trial, precluding any within-corpus replication or assessment of consistency. Single-trial signals carry heightened risk of both type I and type II error, and the effect directions cannot be confirmed or refuted without corroborating studies in comparable populations."},{"id":"claim_22","type":"claim","text":"External validity is constrained by the populations enrolled across the corpus. No trial in this corpus included adults older than 80 years, and racial or ethnic diversity was rarely reported. Furthermore, individuals with obesity above the WHO 2000 threshold of 30 kg/m2, uncontrolled diabetes exceeding the ADA 2024 HbA1c target of 7%, or advanced chronic kidney disease were systematically excluded from most study protocols, limiting generalizability to those higher-risk clinical populations."},{"id":"claim_23","type":"claim","text":"The corpus contains a substantial mechanistic-to-clinical translation gap in several domains. Likewise, Xiao 2021 reported cardioprotective effects of NR reducing infarct size in a rat ischemia-reperfusion model, but the corresponding human evidence—Yu 2025—showed no significant benefit in ischemic cardiomyopathy patients. Cognitive and neurodegenerative outcomes are addressed only by the narrative review of Qader 2025 and a biomarker-only study in neuronal extracellular vesicles (Vreones 2022); no placebo-controlled trial in the corpus assessed cognitive function as a primary endpoint. These disconnects mean that mechanistic plausibility, however strong, does not yet translate into clinically confirmed benefit for the most publicly salient anti-aging claims."},{"id":"claim_24","type":"claim","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 is non-supportive for clinical efficacy or general health-intervention claims; it supports only hypothesis generation and structured follow-up within the limits of indirect evidence. 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."},{"id":"claim_25","type":"claim","text":"This synthesis maps 29 included sources on Nad Effects across 8 outcome classes and 98 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."},{"id":"claim_26","type":"claim","text":"Across 29 curated reference papers, the evidence base for Nad Effects shows a context-dependent profile. Positive signals appear in: contextual other, immune inflammation. Negative signals appear in: longevity, contextual other. Null findings dominate: contextual other, cardiometabolic. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Nad Effects 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."},{"id":"claim_27","type":"claim","text":"The strongest unresolved contrast is the disagreement between Pei 2024 and Curran 2025 on contextual adjacent evidence (severity 5/5), which defines the boundary condition future studies must test rather than smooth over."},{"id":"claim_28","type":"claim","text":"Prior reviews in the corpus (Curran 2025, Han 2022, Safety 2021) 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."},{"id":"claim_29","type":"claim","text":"| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |"},{"id":"claim_30","type":"claim","text":"| cardiometabolic | 0 | 6 | null, unclear | direct interventional hard-endpoint gap |"},{"id":"source_1","type":"source","study":"Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial","year":2023,"doi":"10.1038/s41598-023-29787-3","url":"https://doi.org/10.1038/s41598-023-29787-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_2","type":"source","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","year":2021,"doi":"10.1093/jn/nxab193","url":"https://doi.org/10.1093/jn/nxab193","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_3","type":"source","study":"Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T","year":2024,"doi":"10.1038/s41467-024-53292-4","url":"https://doi.org/10.1038/s41467-024-53292-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_4","type":"source","study":"Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models","year":2025,"doi":"10.1038/s41598-025-95735-y","url":"https://doi.org/10.1038/s41598-025-95735-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_5","type":"source","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","year":2022,"doi":"10.1007/s11357-022-00705-1","url":"https://doi.org/10.1007/s11357-022-00705-1","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_6","type":"source","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","year":2020,"doi":"10.1186/s12882-020-02006-1","url":"https://doi.org/10.1186/s12882-020-02006-1","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_7","type":"source","study":"Cardioprotecive Properties of Known Agents in Rat Ischemia-Reperfusion Model Under Clinically Relevant Conditions: Only the NAD Precursor Nicotinamide Riboside Reduces Infarct Size in Presence of Fentanyl, Midazolam and Cangrelor, but Not Propofol","year":2021,"doi":"10.3389/fcvm.2021.712478","url":"https://doi.org/10.3389/fcvm.2021.712478","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_8","type":"source","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","year":2022,"doi":"10.3390/nu14112219","url":"https://doi.org/10.3390/nu14112219","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_9","type":"source","study":"Refining Prognosis in Cirrhosis Patients With Ascites: Impact of Acute vs. Non‐Acute Decompensation","year":2025,"doi":"10.1111/apt.70302","url":"https://doi.org/10.1111/apt.70302","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_10","type":"source","study":"Effect of Nicotinamide Adenine Dinucleotide on Heart Failure Caused by Ischemic Cardiomyopathy: A Randomized, Placebo-Controlled Trial","year":2025,"doi":"10.1007/s40256-025-00764-7","url":"https://doi.org/10.1007/s40256-025-00764-7","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_11","type":"source","study":"NAD metabolism modulates inflammation and mitochondria function in diabetic kidney disease","year":2023,"doi":"10.1016/j.jbc.2023.104975","url":"https://doi.org/10.1016/j.jbc.2023.104975","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_12","type":"source","study":"Effects of Nicotinamide Adenine Dinucleotide on Older Patients with Heart Failure","year":2024,"doi":"10.31083/j.rcm2508297","url":"https://doi.org/10.31083/j.rcm2508297","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_13","type":"source","study":"Relationship between sperm NAD + concentration and reproductive aging in normozoospermia men:A Cohort study","year":2022,"doi":"10.1186/s12894-022-01107-3","url":"https://doi.org/10.1186/s12894-022-01107-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_14","type":"source","study":"NAD+-Increasing Strategies to Improve Cardiometabolic Health?","year":2022,"doi":"10.3389/fendo.2021.815565","url":"https://doi.org/10.3389/fendo.2021.815565","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_15","type":"source","study":"Nicotinamide Riboside Supplementation for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Midlife and Older Adults","year":2022,"doi":"10.3389/fcvm.2022.881703","url":"https://doi.org/10.3389/fcvm.2022.881703","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_16","type":"source","study":"The complexity of nicotinamide adenine dinucleotide (NAD), hypoxic, and aryl hydrocarbon receptor cell signaling in chronic kidney disease","year":2023,"doi":"10.1186/s12967-023-04584-8","url":"https://doi.org/10.1186/s12967-023-04584-8","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_17","type":"source","study":"Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study","year":2021,"doi":"10.1186/s12970-021-00442-4","url":"https://doi.org/10.1186/s12970-021-00442-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_18","type":"source","study":"A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models","year":2025,"doi":"10.1186/s12868-025-00937-9","url":"https://doi.org/10.1186/s12868-025-00937-9","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_19","type":"source","study":"Nicotinamide Mononucleotide Restores NAD + Levels to Alleviate LPS-Induced Inflammation via the TLR4/NF-κB/MAPK Signaling Pathway in Mice Granulosa Cells","year":2024,"doi":"10.3390/antiox14010039","url":"https://doi.org/10.3390/antiox14010039","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_20","type":"source","study":"Rebalancing of mitochondrial homeostasis through an NAD + -SIRT1 pathway preserves intestinal barrier function in severe malnutrition","year":2023,"doi":"10.1016/j.ebiom.2023.104809","url":"https://doi.org/10.1016/j.ebiom.2023.104809","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_21","type":"source","study":"Sauchinone alleviates dextran sulfate sodium-induced ulcerative colitis via NAD(P)H dehydrogenase [quinone] 1/NF-kB pathway and gut microbiota","year":2023,"doi":"10.3389/fmicb.2022.1084257","url":"https://doi.org/10.3389/fmicb.2022.1084257","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_22","type":"source","study":"A Liposomal Formulation Enhances the Anti-Senescence Properties of Nicotinamide Adenine-Dinucleotide (NAD + ) in Endothelial Cells and Keratinocytes","year":2025,"doi":"10.3390/cimb47090722","url":"https://doi.org/10.3390/cimb47090722","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_23","type":"source","study":"Trigonelline is an NAD + precursor that improves muscle function during ageing and is reduced in human sarcopenia","year":2024,"doi":"10.1038/s42255-024-00997-x","url":"https://doi.org/10.1038/s42255-024-00997-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_24","type":"source","study":"The impacts of continuous improvements in air quality on mortality in Beijing: A longitudinal comparative study.","year":2022,"doi":"10.1016/j.chemosphere.2021.132893","url":"https://doi.org/10.1016/j.chemosphere.2021.132893","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_25","type":"source","study":"Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin","year":2022,"doi":"10.1111/acel.13754","url":"https://doi.org/10.1111/acel.13754","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_26","type":"source","study":"Safety Evaluation for Restorin® NMN, a NAD+ Precursor","year":2021,"doi":"10.3389/fphar.2021.749727","url":"https://doi.org/10.3389/fphar.2021.749727","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_27","type":"source","study":"Unveiling the role of NAD glycohydrolase CD38 in aging and age-related diseases: insights from bibliometric analysis and comprehensive review","year":2025,"doi":"10.3389/fimmu.2025.1579924","url":"https://doi.org/10.3389/fimmu.2025.1579924","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_28","type":"source","study":"Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD + in healthy middle-aged and older adults","year":2018,"doi":"10.1038/s41467-018-03421-7","url":"https://doi.org/10.1038/s41467-018-03421-7","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_29","type":"source","study":"Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD + Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures","year":2019,"doi":"10.1016/j.celrep.2019.07.043","url":"https://doi.org/10.1016/j.celrep.2019.07.043","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_30","type":"source","study":"**Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_31","type":"source","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.","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_32","type":"source","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.","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_33","type":"source","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.","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_34","type":"source","study":"ADA 2024","year":null,"doi":"10.2337/dc24-S006","url":"https://doi.org/10.2337/dc24-S006","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_35","type":"source","study":"WHO 2000","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_36","type":"source","study":"Ioannidis 2005","year":null,"doi":"10.1371/journal.pmed.0020124","url":"https://doi.org/10.1371/journal.pmed.0020124","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"}],"edges":[{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_1","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_2","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_3","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_4","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_5","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_6","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_7","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_8","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_9","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_10","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_11","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_12","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_13","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_14","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_15","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_16","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_17","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_18","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_19","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_20","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_21","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_22","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_23","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_24","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_25","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_26","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_27","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_28","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_29","type":"contains_claim"},{"from":"ca403171-b282-4695-8058-9dd6bfe3754b","to":"claim_30","type":"contains_claim"}],"screening":{"identified":29,"screened":29,"excluded":0,"included":29,"included_or_retained":29,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"29 candidate receipts retained after source retrieval, deduplication, and topic filtering. 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