source · application/json
source_15109964045b48d0
sha256 e6436ab2ee87c848ce11fc74555c1ae179fcb07f8fe7793e50e85777dfddfee8
by researka:v2 · 2026-06-19 10:16:13.475705+04:00
{"publication_id": "409d864f-0ec9-426f-a90e-da69e4fd0671", "traces": [{"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "Evidence-honesty note: 8/12 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. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.", "claim_id": "claim_1"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "This paper synthesizes evidence on NAD+ metabolism effects across 12 included source papers and 804 high-confidence extracted claims.", "claim_id": "claim_2"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 12 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence, with 0 cross-study disagreements across the evidence base.", "claim_id": "claim_3"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "No single positive outcome class dominates the retained corpus; null signals cluster in the contextual adjacent evidence, cardiometabolic, safety and comorbidity outcome classes, and negative signals cluster in no dominant outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "claim_id": "claim_4"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "The conclusion is that NAD+ metabolism effects should be treated as a bounded geroscience hypothesis: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.", "claim_id": "claim_5"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "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-2026-06-19T04-15-04Z`.", "claim_id": "claim_6"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text.", "claim_id": "claim_7"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses).", "claim_id": "claim_8"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, 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.", "claim_id": "claim_9"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.", "claim_id": "claim_10"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.", "claim_id": "claim_11"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "claim_id": "claim_12"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "| Contextual Adjacent Evidence | n=5; claims=146 | no extracted directional signal in 5/5 sources | 3 indirect; 2 review | limited corpus depth in this outcome class |", "claim_id": "claim_13"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.", "claim_id": "claim_14"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "5 included sources were assigned to this outcome class. Directional coding: null=5. Directness coding: indirect=3, review=2.", "claim_id": "claim_15"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "3 included sources were assigned to this outcome class. Directional coding: null=1, unclear=2. 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Directional coding: null=1. Directness coding: review=1.", "claim_id": "claim_18"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.", "claim_id": "claim_19"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "Several mechanistically appealing but clinically actionable effects — for example, the ARDS-ferroptosis link in Gao 2026 (P < 0.0001 in the cited source), the cognitive outcomes in Yulug 2023, and the menopause-symptom signal in Holmes 2026 (NCT04841499) — are each carried by a single trial within this corpus, so no within-corpus replication is possible and any effect estimate rests on one design, one population, and one analytic pipeline. Connell 2021 likewise represents the only formally enrolled skeletal-muscle-function RCT of a tryptophan/niacin/nicotinamide combination in physically compromised older adults, and although it reported more than 40 p-values, the vast majority were non-significant (P ≥ 0.05 across the muscle-function panel), so the function-null signal that contrasts with biomarker-positive precursor trials cannot be triangulated against an independent muscle-function dataset in this bundle.", "claim_id": "claim_20"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "Endpoint scope is narrower than the mechanistic literature would suggest. Safety follow-up in Conze 2019 is limited to the randomized, double-blind, placebo-controlled duration and does not capture long-term adverse-event rates, drug-drug interactions with common cardiometabolic medications, or effects in renally or hepatically impaired users.", "claim_id": "claim_21"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "The mechanism-to-clinic gap is particularly visible in the biomarker-versus-function divergence. This is consistent with the broader methodological caution that surrogate associations do not guarantee hard-outcome validity (Ioannidis 2005), so the headline claim that NAD+ metabolism shows a context-dependent profile rests on biomarker evidence with limited paired functional confirmation, and the boundary conditions of any clinical translation remain to be established.", "claim_id": "claim_22"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "For NAD+ metabolism effects, the final interpretation is deliberately tiered: the retained clinical and adjacent 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.", "claim_id": "claim_23"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "This synthesis maps 12 included sources on NAD+ Metabolism Effects across 5 outcome classes with no cross-study disagreements surfaced. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.", "claim_id": "claim_24"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "Across 12 curated reference papers, the evidence base for NAD+ shows a context-dependent profile. Null findings dominate: contextual other, cardiometabolic. 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.", "claim_id": "claim_25"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "In animal/preclinical evidence, prior reviews in the corpus (Chen 2024) emphasize convergent signals on NAD+ Metabolism 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.", "claim_id": "claim_26"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials", "url": "https://doi.org/10.1007/s11892-024-01557-z"}], "claim": "| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |", "claim_id": "claim_27"}, {"candidate_sources": [{"doi": "10.1038/s41598-023-29787-3", "study": "Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial", "url": "https://doi.org/10.1038/s41598-023-29787-3"}, {"doi": "10.1093/jn/nxab193", "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", "url": "https://doi.org/10.1093/jn/nxab193"}, {"doi": "10.1186/s40035-023-00336-2", "study": "Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial", "url": "https://doi.org/10.1186/s40035-023-00336-2"}, {"doi": "10.1186/s12868-025-00937-9", "study": "A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models", "url": "https://doi.org/10.1186/s12868-025-00937-9"}, {"doi": "10.1007/s11892-024-01557-z", "study": "Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and 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