Derivation Web

source_19d6be67e5254bca

by researka:v2 · 2026-06-21 20:56:16.386543+04:00

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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. 18/19 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.", "type": "claim"}, {"id": "claim_2", "text": "This paper synthesizes evidence on NAD+ metabolism effects across 19 accepted source papers and 1054 high-confidence extracted claims.", "type": "claim"}, {"id": "claim_3", "text": "The evidence profile contains 1 direct clinical source, 18 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence, with 18 cross-study disagreements across the evidence base.", "type": "claim"}, {"id": "claim_4", "text": "Positive study-level signals are summarized in the frailty outcome class, null signals in the contextual adjacent evidence, dosing and pharmacokinetics, cardiometabolic outcome classes, and negative signals in no dominant outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "type": "claim"}, {"id": "claim_5", "text": "The conclusion is that NAD+ metabolism effects remains a bounded geroscience case: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.", "type": "claim"}, {"id": "claim_6", "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_metabolism_effects-v06-DAILY-2026-06-21T16-27-12Z-R2`.", "type": "claim"}, {"id": "claim_7", "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_8", "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_9", "text": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, dosing and pharmacokinetics, frailty, 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_10", "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_11", "text": "Signal-accounting note: biomarker-positive source-level findings are separated from clinical-endpoint mixed/null rows; biomarker elevation is not counted as clinical efficacy unless the mapped outcome class and endpoint support it.", "type": "claim"}, {"id": "claim_12", "text": "Role-accounting note: retained translational or mechanistic-with-human-correlational evidence is mapped by its public outcome and directness row; preclinical or mechanistic records that are not retained in the source map are excluded from clinical outcome-class tallies.", "type": "claim"}, {"id": "claim_13", "text": "Tension-accounting note: disagreement counts are claim-level. Substantive tension still remains between biomarker-elevating studies and mixed/null clinical-endpoint studies across cognition, menopause, acute-care, so these contrasts are treated as unresolved evidence gaps.", "type": "claim"}, {"id": "claim_14", "text": "Yulug 2023: Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial: outcome=Contextual Adjacent Evidence; directness=review; tier=B2.", "type": "claim"}, {"id": "claim_15", "text": "In animal/preclinical evidence, Elhassan 2019: Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD + Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures: outcome=Muscle Function; directness=indirect; tier=B2.", "type": "claim"}, {"id": "claim_16", "text": "In animal/preclinical evidence, Chen 2024: Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials: outcome=Cardiometabolic; directness=review; tier=B1.", "type": "claim"}, {"id": "claim_17", "text": "Ryu 2022: Nicotinamide riboside and caffeine partially restore diminished NAD availability but not altered energy metabolism in Alzheimer's disease: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.", "type": "claim"}, {"id": "claim_18", "text": "Holmes 2026: Nicotinamide riboside and pterostilbene reduces frequency and severity of undesirable symptoms of the menopause transition: an open-label, pilot clinical trial: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.", "type": "claim"}, {"id": "claim_19", "text": "Christen 2026: The differential impact of three different NAD + boosters on circulatory NAD and microbial metabolism in humans: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.", "type": "claim"}, {"id": "claim_20", "text": "Yu 2026: Double‐Pronged NAD Preservation: Delaying Cellular Senescence and Initiating Musculoskeletal Regeneration: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.", "type": "claim"}, {"id": "claim_21", "text": "In animal/preclinical evidence, Bozon 2025: Maternal Circulatory NAD Precursor Levels and the Yolk Sac Determine NAD Deficiency‐Driven Congenital Malformation Risk: outcome=Deficiency Prevalence; directness=indirect; tier=B2.", "type": "claim"}, {"id": "claim_22", "text": "In animal/preclinical evidence, Richard 2026: NAD + and Sirt5 restore mitochondrial bioenergetics failure and improve locomotor defects caused by sucla2 mutations: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.", "type": "claim"}, {"id": "claim_23", "text": "Visalli 2026: Mitochondrial Resilience in Glaucoma: Targeting NAD + Metabolism and Oxidative Stress in Retinal Ganglion Cell Degeneration with Nicotinamide Riboside and Berberine: Preliminary Clinical Evidence: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.", "type": "claim"}, {"id": "claim_24", "text": "In animal/preclinical evidence, Harasim-Krawcewicz 2026: NAD + Enhancer Nicotinamide Riboside Alters Extracellular Purine Metabolism in Human Endothelial Cells: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.", "type": "claim"}, {"id": "claim_25", "text": "Imai 2025: From Bench to Clinic: The 2024 FASEB Scientific Research Conference on NAD Metabolism and Signaling: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.", "type": "claim"}, {"id": "claim_26", "text": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "type": "claim"}, {"id": "claim_27", "text": "| Contextual Adjacent Evidence | n=9; claims=176 | no extracted directional signal in 9/9 sources | 8 indirect; 1 review | limited corpus depth in this outcome class |", "type": "claim"}, {"id": "claim_28", "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_29", "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_30", "text": "9 included sources were assigned to this outcome class. Directional coding: null=9. Directness coding: indirect=8, review=1.", "type": "claim"}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1016/j.isci.2026.114764", "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": "The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation", "type": "source", "url": "https://doi.org/10.1016/j.isci.2026.114764", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41598-023-29787-3", "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": "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_3", "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": "review-level", "doi": "10.1186/s40035-023-00336-2", "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": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "type": "source", "url": "https://doi.org/10.1186/s40035-023-00336-2", "year": 2023}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1007/s11892-024-01557-z", "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": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "type": "source", "url": "https://doi.org/10.1007/s11892-024-01557-z", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1096/fba.2025-00014", "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": "Oral MIB‐626 (β Nicotinamide Mononucleotide) Safely Raises Blood Nicotinamide Adenine Dinucleotide Levels in Hospitalized Patients With COVID‐19 and Acute Kidney Injury: A Randomized Controlled Trial", "type": "source", "url": "https://doi.org/10.1096/fba.2025-00014", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1111/acel.13658", "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": "Nicotinamide riboside and caffeine partially restore diminished NAD availability but not altered energy metabolism in Alzheimer's disease", "type": "source", "url": "https://doi.org/10.1111/acel.13658", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fragi.2026.1773667", "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 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_9", "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": "10.1111/acel.70468", "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": "Double‐Pronged NAD Preservation: Delaying Cellular Senescence and Initiating Musculoskeletal Regeneration", "type": "source", "url": "https://doi.org/10.1111/acel.70468", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s42255-024-00997-x", "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": "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": "10.1172/jci.insight.181812", "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": "NAD + and Sirt5 restore mitochondrial bioenergetics failure and improve locomotor defects caused by sucla2 mutations", "type": "source", "url": "https://doi.org/10.1172/jci.insight.181812", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1096/fj.202500708RR", "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": "Maternal Circulatory NAD Precursor Levels and the Yolk Sac Determine NAD Deficiency‐Driven Congenital Malformation Risk", "type": "source", "url": "https://doi.org/10.1096/fj.202500708RR", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/diseases14020056", "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": "Mitochondrial Resilience in Glaucoma: Targeting NAD + Metabolism and Oxidative Stress in Retinal Ganglion Cell Degeneration with Nicotinamide Riboside and Berberine: Preliminary Clinical Evidence", "type": "source", "url": "https://doi.org/10.3390/diseases14020056", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ijms27073267", "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": "NAD + Enhancer Nicotinamide Riboside Alters Extracellular Purine Metabolism in Human Endothelial Cells", "type": "source", "url": "https://doi.org/10.3390/ijms27073267", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s10020-025-01394-0", "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": "From Bench to Clinic: The 2024 FASEB Scientific Research Conference on NAD Metabolism and Signaling", "type": "source", "url": "https://doi.org/10.1186/s10020-025-01394-0", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1038/s41598-019-46120-z", "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": "Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults", "type": "source", "url": "https://doi.org/10.1038/s41598-019-46120-z", "year": 2019}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41467-018-03421-7", "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": "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": "10.1016/j.celrep.2019.07.043", "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": "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_20", "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_21", "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_22", "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_23", "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": "10.1371/journal.pmed.0020124", "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": "Ioannidis 2005", "type": "source", "url": "https://doi.org/10.1371/journal.pmed.0020124", "year": null}], "publication_id": "529fbc6c-66ad-49b5-910a-f2b076cb190c", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", "included"], "identified": 19, "included": 19, "included_or_retained": 19, "screened": 19, "wording": "19 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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