Derivation Web

source_8f7d91959f024162

by researka:v2 · 2026-06-08 22:16:13.333406+04:00

{"publication_id": "ca403171-b282-4695-8058-9dd6bfe3754b", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "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_effects-v06-DAILY-2026-06-07T05-02-41Z-R3`.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "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_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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "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). Ratings recorded in `risk_of_bias.json`.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "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_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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "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_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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "| 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 |", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "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_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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "6 included sources were assigned to this outcome class. Directional coding: null=3, unclear=3. Directness coding: indirect=5, review=1.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "claim_id": "claim_16"}, {"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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.", "claim_id": "claim_17"}, {"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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "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.", "claim_id": "claim_28"}, {"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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |", "claim_id": "claim_29"}, {"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": "10.1038/s41467-024-53292-4", "study": "Development of a 31 P magnetic resonance spectroscopy technique to quantify NADH and NAD + at 3 T", "url": "https://doi.org/10.1038/s41467-024-53292-4"}, {"doi": "10.1038/s41598-025-95735-y", "study": "Meta-analysis of niacin and NAD metabolite treatment in infectious disease animal studies suggests benefit but requires confirmation in clinically relevant models", "url": "https://doi.org/10.1038/s41598-025-95735-y"}, {"doi": "10.1007/s11357-022-00705-1", "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", "url": "https://doi.org/10.1007/s11357-022-00705-1"}], "claim": "| cardiometabolic | 0 | 6 | null, unclear | direct interventional hard-endpoint gap |", "claim_id": "claim_30"}]}

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