{"publication_id":"529fbc6c-66ad-49b5-910a-f2b076cb190c","traces":[{"claim_id":"claim_1","claim":"Evidence-honesty note: 13/19 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. 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.","candidate_sources":[{"study":"The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation","doi":"10.1016/j.isci.2026.114764","url":"https://doi.org/10.1016/j.isci.2026.114764"},{"study":"Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial","doi":"10.1038/s41598-023-29787-3","url":"https://doi.org/10.1038/s41598-023-29787-3"},{"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","doi":"10.1093/jn/nxab193","url":"https://doi.org/10.1093/jn/nxab193"},{"study":"Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial","doi":"10.1186/s40035-023-00336-2","url":"https://doi.org/10.1186/s40035-023-00336-2"},{"study":"Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials","doi":"10.1007/s11892-024-01557-z","url":"https://doi.org/10.1007/s11892-024-01557-z"}]},{"claim_id":"claim_2","claim":"This paper synthesizes evidence on NAD+ metabolism effects across 19 accepted source papers and 1054 high-confidence extracted claims.","candidate_sources":[{"study":"The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation","doi":"10.1016/j.isci.2026.114764","url":"https://doi.org/10.1016/j.isci.2026.114764"},{"study":"Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial","doi":"10.1038/s41598-023-29787-3","url":"https://doi.org/10.1038/s41598-023-29787-3"},{"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","doi":"10.1093/jn/nxab193","url":"https://doi.org/10.1093/jn/nxab193"},{"study":"Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial","doi":"10.1186/s40035-023-00336-2","url":"https://doi.org/10.1186/s40035-023-00336-2"},{"study":"Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials","doi":"10.1007/s11892-024-01557-z","url":"https://doi.org/10.1007/s11892-024-01557-z"}]},{"claim_id":"claim_3","claim":"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.","candidate_sources":[{"study":"The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation","doi":"10.1016/j.isci.2026.114764","url":"https://doi.org/10.1016/j.isci.2026.114764"},{"study":"Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial","doi":"10.1038/s41598-023-29787-3","url":"https://doi.org/10.1038/s41598-023-29787-3"},{"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","doi":"10.1093/jn/nxab193","url":"https://doi.org/10.1093/jn/nxab193"},{"study":"Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial","doi":"10.1186/s40035-023-00336-2","url":"https://doi.org/10.1186/s40035-023-00336-2"},{"study":"Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials","doi":"10.1007/s11892-024-01557-z","url":"https://doi.org/10.1007/s11892-024-01557-z"}]},{"claim_id":"claim_4","claim":"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.","candidate_sources":[{"study":"The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation","doi":"10.1016/j.isci.2026.114764","url":"https://doi.org/10.1016/j.isci.2026.114764"},{"study":"Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial","doi":"10.1038/s41598-023-29787-3","url":"https://doi.org/10.1038/s41598-023-29787-3"},{"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","doi":"10.1093/jn/nxab193","url":"https://doi.org/10.1093/jn/nxab193"},{"study":"Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial","doi":"10.1186/s40035-023-00336-2","url":"https://doi.org/10.1186/s40035-023-00336-2"},{"study":"Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials","doi":"10.1007/s11892-024-01557-z","url":"https://doi.org/10.1007/s11892-024-01557-z"}]},{"claim_id":"claim_5","claim":"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.","candidate_sources":[{"study":"The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation","doi":"10.1016/j.isci.2026.114764","url":"https://doi.org/10.1016/j.isci.2026.114764"},{"study":"Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial","doi":"10.1038/s41598-023-29787-3","url":"https://doi.org/10.1038/s41598-023-29787-3"},{"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","doi":"10.1093/jn/nxab193","url":"https://doi.org/10.1093/jn/nxab193"},{"study":"Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial","doi":"10.1186/s40035-023-00336-2","url":"https://doi.org/10.1186/s40035-023-00336-2"},{"study":"Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials","doi":"10.1007/s11892-024-01557-z","url":"https://doi.org/10.1007/s11892-024-01557-z"}]},{"claim_id":"claim_6","claim":"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`.","candidate_sources":[{"study":"The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation","doi":"10.1016/j.isci.2026.114764","url":"https://doi.org/10.1016/j.isci.2026.114764"},{"study":"Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial","doi":"10.1038/s41598-023-29787-3","url":"https://doi.org/10.1038/s41598-023-29787-3"},{"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","doi":"10.1093/jn/nxab193","url":"https://doi.org/10.1093/jn/nxab193"},{"study":"Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial","doi":"10.1186/s40035-023-00336-2","url":"https://doi.org/10.1186/s40035-023-00336-2"},{"study":"Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials","doi":"10.1007/s11892-024-01557-z","url":"https://doi.org/10.1007/s11892-024-01557-z"}]},{"claim_id":"claim_7","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 sidecar when populated, and claim registry) rather than from re-parsed full text.","candidate_sources":[{"study":"The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation","doi":"10.1016/j.isci.2026.114764","url":"https://doi.org/10.1016/j.isci.2026.114764"},{"study":"Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial","doi":"10.1038/s41598-023-29787-3","url":"https://doi.org/10.1038/s41598-023-29787-3"},{"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","doi":"10.1093/jn/nxab193","url":"https://doi.org/10.1093/jn/nxab193"},{"study":"Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial","doi":"10.1186/s40035-023-00336-2","url":"https://doi.org/10.1186/s40035-023-00336-2"},{"study":"Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials","doi":"10.1007/s11892-024-01557-z","url":"https://doi.org/10.1007/s11892-024-01557-z"}]},{"claim_id":"claim_8","claim":"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.","candidate_sources":[{"study":"The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation","doi":"10.1016/j.isci.2026.114764","url":"https://doi.org/10.1016/j.isci.2026.114764"},{"study":"Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial","doi":"10.1038/s41598-023-29787-3","url":"https://doi.org/10.1038/s41598-023-29787-3"},{"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","doi":"10.1093/jn/nxab193","url":"https://doi.org/10.1093/jn/nxab193"},{"study":"Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial","doi":"10.1186/s40035-023-00336-2","url":"https://doi.org/10.1186/s40035-023-00336-2"},{"study":"Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials","doi":"10.1007/s11892-024-01557-z","url":"https://doi.org/10.1007/s11892-024-01557-z"}]},{"claim_id":"claim_9","claim":"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.","candidate_sources":[{"study":"The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation","doi":"10.1016/j.isci.2026.114764","url":"https://doi.org/10.1016/j.isci.2026.114764"},{"study":"Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial","doi":"10.1038/s41598-023-29787-3","url":"https://doi.org/10.1038/s41598-023-29787-3"},{"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","doi":"10.1093/jn/nxab193","url":"https://doi.org/10.1093/jn/nxab193"},{"study":"Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial","doi":"10.1186/s40035-023-00336-2","url":"https://doi.org/10.1186/s40035-023-00336-2"},{"study":"Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials","doi":"10.1007/s11892-024-01557-z","url":"https://doi.org/10.1007/s11892-024-01557-z"}]},{"claim_id":"claim_10","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.","candidate_sources":[{"study":"The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation","doi":"10.1016/j.isci.2026.114764","url":"https://doi.org/10.1016/j.isci.2026.114764"},{"study":"Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial","doi":"10.1038/s41598-023-29787-3","url":"https://doi.org/10.1038/s41598-023-29787-3"},{"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","doi":"10.1093/jn/nxab193","url":"https://doi.org/10.1093/jn/nxab193"},{"study":"Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial","doi":"10.1186/s40035-023-00336-2","url":"https://doi.org/10.1186/s40035-023-00336-2"},{"study":"Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials","doi":"10.1007/s11892-024-01557-z","url":"https://doi.org/10.1007/s11892-024-01557-z"}]},{"claim_id":"claim_11","claim":"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.","candidate_sources":[{"study":"The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation","doi":"10.1016/j.isci.2026.114764","url":"https://doi.org/10.1016/j.isci.2026.114764"},{"study":"Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial","doi":"10.1038/s41598-023-29787-3","url":"https://doi.org/10.1038/s41598-023-29787-3"},{"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","doi":"10.1093/jn/nxab193","url":"https://doi.org/10.1093/jn/nxab193"},{"study":"Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial","doi":"10.1186/s40035-023-00336-2","url":"https://doi.org/10.1186/s40035-023-00336-2"},{"study":"Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials","doi":"10.1007/s11892-024-01557-z","url":"https://doi.org/10.1007/s11892-024-01557-z"}]},{"claim_id":"claim_12","claim":"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.","candidate_sources":[{"study":"The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation","doi":"10.1016/j.isci.2026.114764","url":"https://doi.org/10.1016/j.isci.2026.114764"},{"study":"Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial","doi":"10.1038/s41598-023-29787-3","url":"https://doi.org/10.1038/s41598-023-29787-3"},{"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","doi":"10.1093/jn/nxab193","url":"https://doi.org/10.1093/jn/nxab193"},{"study":"Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial","doi":"10.1186/s40035-023-00336-2","url":"https://doi.org/10.1186/s40035-023-00336-2"},{"study":"Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials","doi":"10.1007/s11892-024-01557-z","url":"https://doi.org/10.1007/s11892-024-01557-z"}]},{"claim_id":"claim_13","claim":"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.","candidate_sources":[{"study":"The NAD-brain pharmacokinetic study of NAD augmentation in blood and brain using oral precursor supplementation","doi":"10.1016/j.isci.2026.114764","url":"https://doi.org/10.1016/j.isci.2026.114764"},{"study":"Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial","doi":"10.1038/s41598-023-29787-3","url":"https://doi.org/10.1038/s41598-023-29787-3"},{"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","doi":"10.1093/jn/nxab193","url":"https://doi.org/10.1093/jn/nxab193"},{"study":"Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial","doi":"10.1186/s40035-023-00336-2","url":"https://doi.org/10.1186/s40035-023-00336-2"},{"study":"Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials","doi":"10.1007/s11892-024-01557-z","url":"https://doi.org/10.1007/s11892-024-01557-z"}]},{"claim_id":"claim_14","claim":"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; 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