Nutrient chapter

NAD+

Metabolic dinucleotide substrate of the reported SELENOO hydrolysis reaction.

91 recorded mechanisms · 9 availability situations · 11 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

A compartment-targeted biosensor estimated free NAD+ in HEK293T cells at 106 micromolar in cytoplasm, 109 micromolar in nucleus and 230 micromolar in mitochondria.
NAD+ → Free NAD+ pools in human HEK293T compartments source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Genetically encoded biosensor with permeabilization calibration in human HEK293T cells.
limitations
These are cell-line estimates with calibration assumptions, not normal human blood ranges or dietary deficiency thresholds.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Different compartments contain different amounts of freely available NAD+.
primary_references
Biosensor reveals multiple sources for mitochondrial NAD⁺. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27313049/ · DOI 10.1126/science.aad5168
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 12–18
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Genetically encoded biosensor with permeabilization calibration in human HEK293T cells. · source_derived_draft · unverified_draft
## nad-plus-free-pools Different compartments contain different amounts of freely available NAD+. A compartment-targeted biosensor estimated free NAD+ in HEK293T cells at 106 micromolar in cytoplasm, 109 micromolar in nucleus and 230 micromolar in mitochondria. Model: Genetically encoded biosensor with permeabilization calibration in human HEK293T cells. Limitations: These are cell-line estimates with calibration assumptions, not normal human blood ranges or dietary deficiency thresholds. Evidence access: Primary full text Biosensor reveals multiple sources for mitochondrial NAD⁺. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27313049/ · DOI 10.1126/science.aad5168
Complete structured claim and evidence
FK866 inhibition of NAMPT depleted nuclear and cytoplasmic free NAD+ with approximate two-hour half-times, versus approximately eight hours in mitochondria; 16 hours reduced free NAD+ by over 85% in all three compartments.
Human nicotinamide phosphoribosyltransferase / NAMPT → Free NAD+ pools in human HEK293T compartments source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Cultured human-cell biosensor experiments.
limitations
Drug-induced loss does not define dietary niacin deficiency or establish equivalent depletion in every tissue.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Blocking recycling empties NAD pools at different speeds.
primary_references
Biosensor reveals multiple sources for mitochondrial NAD⁺. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27313049/ · DOI 10.1126/science.aad5168
trigger_kind
machinery_impairment Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 20–26
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured human-cell biosensor experiments. · source_derived_draft · unverified_draft
## nad-plus-salvage-depletion Blocking recycling empties NAD pools at different speeds. FK866 inhibition of NAMPT depleted nuclear and cytoplasmic free NAD+ with approximate two-hour half-times, versus approximately eight hours in mitochondria; 16 hours reduced free NAD+ by over 85% in all three compartments. Model: Cultured human-cell biosensor experiments. Limitations: Drug-induced loss does not define dietary niacin deficiency or establish equivalent depletion in every tissue. Evidence access: Primary full text Biosensor reveals multiple sources for mitochondrial NAD⁺. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27313049/ · DOI 10.1126/science.aad5168
Complete structured claim and evidence
The PARP inhibitor Tiq-A slowed early nuclear/cytoplasmic NAD+ depletion after NAMPT inhibition, with little effect on mitochondrial depletion.
Human PARP1 → Nucleocytoplasmic NAD depletion during salvage blockade source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Cultured human cells; pharmacological PARP inhibition.
limitations
Tiq-A is not a PARP1-specific genetic experiment, and did not prevent eventual depletion in all compartments.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Consumption can determine how quickly a blocked supply becomes a shortage.
primary_references
Biosensor reveals multiple sources for mitochondrial NAD⁺. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27313049/ · DOI 10.1126/science.aad5168
trigger_kind
machinery_impairment Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 28–34
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured human cells; pharmacological PARP inhibition. · source_derived_draft · unverified_draft
## nad-plus-parp-depletion-rate Consumption can determine how quickly a blocked supply becomes a shortage. The PARP inhibitor Tiq-A slowed early nuclear/cytoplasmic NAD+ depletion after NAMPT inhibition, with little effect on mitochondrial depletion. Model: Cultured human cells; pharmacological PARP inhibition. Limitations: Tiq-A is not a PARP1-specific genetic experiment, and did not prevent eventual depletion in all compartments. Evidence access: Primary full text Biosensor reveals multiple sources for mitochondrial NAD⁺. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27313049/ · DOI 10.1126/science.aad5168
Complete structured claim and evidence
MCART1/SLC25A51-null human cells had reduced mitochondrial NAD+/NADH, TCA-cycle flux, respiration and complex-I activity.
SLC25A51 → Respiration supported by SLC25A51 in human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human cultured-cell knockout, metabolomics and isolated-mitochondrial assays.
limitations
Cellular transporter disruption, not proof that oral NAD crosses all membranes or treats a transporter disorder.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
A functioning NAD supply outside mitochondria cannot compensate for a broken mitochondrial entry route.
primary_references
MCART1/SLC25A51 is required for mitochondrial NAD transport. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33087354/ · DOI 10.1126/sciadv.abe5310
trigger_kind
machinery_impairment Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 36–42
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cultured-cell knockout, metabolomics and isolated-mitochondrial assays. · source_derived_draft · unverified_draft
## nad-plus-slc51-respiration A functioning NAD supply outside mitochondria cannot compensate for a broken mitochondrial entry route. MCART1/SLC25A51-null human cells had reduced mitochondrial NAD+/NADH, TCA-cycle flux, respiration and complex-I activity. Model: Human cultured-cell knockout, metabolomics and isolated-mitochondrial assays. Limitations: Cellular transporter disruption, not proof that oral NAD crosses all membranes or treats a transporter disorder. Evidence access: Primary full text MCART1/SLC25A51 is required for mitochondrial NAD transport. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33087354/ · DOI 10.1126/sciadv.abe5310
Complete structured claim and evidence
Overexpression of human SLC25A52 increased mitochondrial NAD+ in cultured human cells and complemented yeast lacking endogenous mitochondrial NAD transporters.
Human SLC25A52 → Mitochondrial NAD+ content source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human-cell overexpression and yeast complementation.
limitations
Overexpression does not establish normal tissue contribution, redundancy or human treatment efficacy.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
A related transporter can support mitochondrial NAD availability in experimental systems.
primary_references
SLC25A51 is a mammalian mitochondrial NAD+ transporter. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32906142/ · DOI 10.1038/s41586-020-2741-7
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 44–50
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell overexpression and yeast complementation. · source_derived_draft · unverified_draft
## nad-plus-slc52-expression A related transporter can support mitochondrial NAD availability in experimental systems. Overexpression of human SLC25A52 increased mitochondrial NAD+ in cultured human cells and complemented yeast lacking endogenous mitochondrial NAD transporters. Model: Human-cell overexpression and yeast complementation. Limitations: Overexpression does not establish normal tissue contribution, redundancy or human treatment efficacy. Evidence access: Primary full text SLC25A51 is a mammalian mitochondrial NAD+ transporter. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32906142/ · DOI 10.1038/s41586-020-2741-7
Complete structured claim and evidence
Adipogenic induction of cytoplasmic NMNAT2 in mouse 3T3-L1 cells competed with nuclear NMNAT1 for NMN and reduced nuclear NAD+ availability.
Mouse NMNAT2 → Mouse nuclear NMNAT1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse preadipocyte differentiation, enzyme perturbations and compartment measurements.
limitations
Not evidence that human NMN supplements cause weight gain; enzyme location and differentiation state matter.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Two compartments can compete for the same building material.
primary_references
Metabolic regulation of transcription through compartmentalized NAD+ biosynthesis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29748257/ · DOI 10.1126/science.aan5780
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 52–58
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse preadipocyte differentiation, enzyme perturbations and compartment measurements. · source_derived_draft · unverified_draft
## nad-plus-nmnat2-competition Two compartments can compete for the same building material. Adipogenic induction of cytoplasmic NMNAT2 in mouse 3T3-L1 cells competed with nuclear NMNAT1 for NMN and reduced nuclear NAD+ availability. Model: Mouse preadipocyte differentiation, enzyme perturbations and compartment measurements. Limitations: Not evidence that human NMN supplements cause weight gain; enzyme location and differentiation state matter. Evidence access: Primary full text Metabolic regulation of transcription through compartmentalized NAD+ biosynthesis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29748257/ · DOI 10.1126/science.aan5780
Complete structured claim and evidence
Nmnat1 knockdown reduced PARP1-mediated PARylation in mouse 3T3-L1 preadipocytes; catalytically active but not inactive NMNAT1 rescued the activity.
Mouse nuclear NMNAT1 → Mouse PARP1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse shRNA and enzyme re-expression experiments.
limitations
PARP activity is not a direct measurement of all nuclear NAD-dependent reactions.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
DNA-associated enzymes can depend on local NAD production.
primary_references
Metabolic regulation of transcription through compartmentalized NAD+ biosynthesis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29748257/ · DOI 10.1126/science.aan5780
trigger_kind
machinery_impairment Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 60–66
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse shRNA and enzyme re-expression experiments. · source_derived_draft · unverified_draft
## nad-plus-nmnat1-loss DNA-associated enzymes can depend on local NAD production. Nmnat1 knockdown reduced PARP1-mediated PARylation in mouse 3T3-L1 preadipocytes; catalytically active but not inactive NMNAT1 rescued the activity. Model: Mouse shRNA and enzyme re-expression experiments. Limitations: PARP activity is not a direct measurement of all nuclear NAD-dependent reactions. Evidence access: Primary full text Metabolic regulation of transcription through compartmentalized NAD+ biosynthesis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29748257/ · DOI 10.1126/science.aan5780
Complete structured claim and evidence
In mouse preadipocytes, PARP1-dependent ADP-ribosylation repressed C/EBP beta adipogenic transcription; reduced nuclear NAD synthesis relieved this repression.
Mouse PARP1 → Mouse C/EBP beta / Cebpb source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse 3T3-L1 transcription and differentiation experiments.
limitations
Cell differentiation mechanism, not a universal whole-body fat response.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
A local NAD change can alter a gene program through protein modification.
primary_references
Metabolic regulation of transcription through compartmentalized NAD+ biosynthesis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29748257/ · DOI 10.1126/science.aan5780
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 68–74
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse 3T3-L1 transcription and differentiation experiments. · source_derived_draft · unverified_draft
## nad-plus-parp-cebpb A local NAD change can alter a gene program through protein modification. In mouse preadipocytes, PARP1-dependent ADP-ribosylation repressed C/EBP beta adipogenic transcription; reduced nuclear NAD synthesis relieved this repression. Model: Mouse 3T3-L1 transcription and differentiation experiments. Limitations: Cell differentiation mechanism, not a universal whole-body fat response. Evidence access: Primary full text Metabolic regulation of transcription through compartmentalized NAD+ biosynthesis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29748257/ · DOI 10.1126/science.aan5780
Complete structured claim and evidence
Increasing NMN relative to NAD+ increased NADase activity of purified human SARM1 residues 28–724, which retain ARM, SAM and TIR domains but lack the mitochondrial targeting sequence.
NMN → Human SARM1 residues 28–724 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Purified human construct; NMR activity assays and cell experiments.
limitations
NAD+ is also the catalytic substrate, so activity cannot be inferred from ratio alone across all conditions. This does not show oral NMN causes nerve injury.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
The balance between a precursor and finished NAD can activate a destructive feedback loop.
primary_references
SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 76–82
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human construct; NMR activity assays and cell experiments. · source_derived_draft · unverified_draft
## nad-plus-sarm-ratio The balance between a precursor and finished NAD can activate a destructive feedback loop. Increasing NMN relative to NAD+ increased NADase activity of purified human SARM1 residues 28–724, which retain ARM, SAM and TIR domains but lack the mitochondrial targeting sequence. Model: Purified human construct; NMR activity assays and cell experiments. Limitations: NAD+ is also the catalytic substrate, so activity cannot be inferred from ratio alone across all conditions. This does not show oral NMN causes nerve injury. Evidence access: Primary full text SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009
Complete structured claim and evidence
NMN bound the purified Drosophila SARM1 ARM domain at approximately 6.39 micromolar dissociation constant, with one ligand per domain.
NMN → Drosophila SARM1 ARM domain residues 307–678 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Drosophila-domain ITC and structural experiments.
limitations
The binding affinity is for a fly domain, not a full-length human protein or a human toxicity threshold.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
The activating precursor has a directly measured binding site.
primary_references
SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 84–90
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Drosophila-domain ITC and structural experiments. · source_derived_draft · unverified_draft
## nad-plus-sarm-nmn-binding The activating precursor has a directly measured binding site. NMN bound the purified Drosophila SARM1 ARM domain at approximately 6.39 micromolar dissociation constant, with one ligand per domain. Model: Drosophila-domain ITC and structural experiments. Limitations: The binding affinity is for a fly domain, not a full-length human protein or a human toxicity threshold. Evidence access: Primary full text SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009
Complete structured claim and evidence
NAD+ bound the same Drosophila SARM1 ARM-domain regulatory site with approximately 54.2 micromolar dissociation constant; competition assays supported opposing occupancy by NAD+ and NMN.
NAD+ → Drosophila SARM1 ARM domain residues 307–678 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Drosophila-domain ITC and NMR competition.
limitations
Species/domain-specific affinity; separate from catalytic-site kinetics.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
NAD can help restrain the switch at a regulatory site while also being its substrate.
primary_references
SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 92–98
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Drosophila-domain ITC and NMR competition. · source_derived_draft · unverified_draft
## nad-plus-sarm-nad-binding NAD can help restrain the switch at a regulatory site while also being its substrate. NAD+ bound the same Drosophila SARM1 ARM-domain regulatory site with approximately 54.2 micromolar dissociation constant; competition assays supported opposing occupancy by NAD+ and NMN. Model: Drosophila-domain ITC and NMR competition. Limitations: Species/domain-specific affinity; separate from catalytic-site kinetics. Evidence access: Primary full text SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009
Complete structured claim and evidence
Aged mouse liver and white adipose tissue accumulated CD38-positive immune cells, including macrophages/monocytes, with increased expression per cell in several comparisons.
Inflammatory-cell accumulation during mouse aging → Mouse CD38 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Young versus aged mice; flow cytometry, histology and macrophage experiments.
limitations
Cell abundance and expression observations do not alone quantify absolute tissue NAD flux.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
More NAD-consuming immune cells can change a tissue metabolite pool.
primary_references
CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33199925/ · DOI 10.1038/s42255-020-00298-z
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 100–106
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Young versus aged mice; flow cytometry, histology and macrophage experiments. · source_derived_draft · unverified_draft
## nad-plus-aging-cd38 More NAD-consuming immune cells can change a tissue metabolite pool. Aged mouse liver and white adipose tissue accumulated CD38-positive immune cells, including macrophages/monocytes, with increased expression per cell in several comparisons. Model: Young versus aged mice; flow cytometry, histology and macrophage experiments. Limitations: Cell abundance and expression observations do not alone quantify absolute tissue NAD flux. Evidence access: Primary full text CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33199925/ · DOI 10.1038/s42255-020-00298-z
Complete structured claim and evidence
Senescent-cell-associated inflammatory signals promoted CD38 expression; reducing senescent-cell burden partially restored NAD+ in the reported mouse experiments.
Secretory factors from senescent mouse-cell models → Mouse CD38 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Senescent-cell conditioned media and mouse interventions.
limitations
Partial rescue supports a contributing mechanism, not a single cause of every age-associated NAD decline.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Signals from one cell population can change NAD availability in another.
primary_references
CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33199925/ · DOI 10.1038/s42255-020-00298-z
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 108–114
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Senescent-cell conditioned media and mouse interventions. · source_derived_draft · unverified_draft
## nad-plus-sasp-cd38 Signals from one cell population can change NAD availability in another. Senescent-cell-associated inflammatory signals promoted CD38 expression; reducing senescent-cell burden partially restored NAD+ in the reported mouse experiments. Model: Senescent-cell conditioned media and mouse interventions. Limitations: Partial rescue supports a contributing mechanism, not a single cause of every age-associated NAD decline. Evidence access: Primary full text CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33199925/ · DOI 10.1038/s42255-020-00298-z
Complete structured claim and evidence
The study linked extracellular CD38 enzymatic activity to NMN degradation and lower precursor availability; selective blockade of ecto-CD38 increased NAD+ in mouse experiments.
Mouse CD38 → NMN source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse biochemical, cellular and ecto-CD38 antibody experiments.
limitations
Not established clinical benefit from an over-the-counter CD38 inhibitor.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
A precursor can be destroyed before a neighboring cell uses it.
primary_references
CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33199925/ · DOI 10.1038/s42255-020-00298-z
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 116–122
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse biochemical, cellular and ecto-CD38 antibody experiments. · source_derived_draft · unverified_draft
## nad-plus-ecto-cd38-nmn A precursor can be destroyed before a neighboring cell uses it. The study linked extracellular CD38 enzymatic activity to NMN degradation and lower precursor availability; selective blockade of ecto-CD38 increased NAD+ in mouse experiments. Model: Mouse biochemical, cellular and ecto-CD38 antibody experiments. Limitations: Not established clinical benefit from an over-the-counter CD38 inhibitor. Evidence access: Primary full text CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33199925/ · DOI 10.1038/s42255-020-00298-z
Complete structured claim and evidence
Isotope tracing found a median tissue NAD+ decrease of about 30% in aged mice while absolute synthesis was maintained in most tissues through faster turnover of the smaller pool.
NAD turnover in aged mice → Absolute NAD biosynthetic flux in mice source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse isotope tracing and mass spectrometry across tissues.
limitations
Tissue-specific animal flux; expression of one enzyme or a static human blood test cannot substitute for this measurement.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
A smaller pool does not necessarily mean slower production.
primary_references
NAD+ flux is maintained in aged mice despite lower tissue concentrations. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34559996/ · DOI 10.1016/j.cels.2021.09.001
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 124–130
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse isotope tracing and mass spectrometry across tissues. · source_derived_draft · unverified_draft
## nad-plus-aging-flux A smaller pool does not necessarily mean slower production. Isotope tracing found a median tissue NAD+ decrease of about 30% in aged mice while absolute synthesis was maintained in most tissues through faster turnover of the smaller pool. Model: Mouse isotope tracing and mass spectrometry across tissues. Limitations: Tissue-specific animal flux; expression of one enzyme or a static human blood test cannot substitute for this measurement. Evidence access: Primary full text NAD+ flux is maintained in aged mice despite lower tissue concentrations. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34559996/ · DOI 10.1016/j.cels.2021.09.001
Complete structured claim and evidence
Calorie restriction partially mitigated age-associated NAD+ decline by decreasing consumption in the mouse isotope-tracing study.
Calorie restriction in mice → NAD consumption flux in mice source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Calorie-restricted versus control mice.
limitations
Not a universal fasting schedule or demonstrated human lifespan mechanism.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Changing demand can preserve a metabolite without increasing supply.
primary_references
NAD+ flux is maintained in aged mice despite lower tissue concentrations. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34559996/ · DOI 10.1016/j.cels.2021.09.001
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 132–138
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Calorie-restricted versus control mice. · source_derived_draft · unverified_draft
## nad-plus-calorie-restriction-flux Changing demand can preserve a metabolite without increasing supply. Calorie restriction partially mitigated age-associated NAD+ decline by decreasing consumption in the mouse isotope-tracing study. Model: Calorie-restricted versus control mice. Limitations: Not a universal fasting schedule or demonstrated human lifespan mechanism. Evidence access: Primary full text NAD+ flux is maintained in aged mice despite lower tissue concentrations. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34559996/ · DOI 10.1016/j.cels.2021.09.001
Complete structured claim and evidence
Acute LPS inflammatory stress reduced NAD+ by impairing synthesis in both young and aged mice.
Acute LPS inflammatory stress in mice → Absolute NAD biosynthetic flux in mice source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse isotope-tracing intervention.
limitations
LPS challenge is not equivalent to every chronic inflammatory condition.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Acute inflammation can impair supply through a different pattern from ordinary aging.
primary_references
NAD+ flux is maintained in aged mice despite lower tissue concentrations. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34559996/ · DOI 10.1016/j.cels.2021.09.001
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 140–146
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse isotope-tracing intervention. · source_derived_draft · unverified_draft
## nad-plus-lps-synthesis Acute inflammation can impair supply through a different pattern from ordinary aging. Acute LPS inflammatory stress reduced NAD+ by impairing synthesis in both young and aged mice. Model: Mouse isotope-tracing intervention. Limitations: LPS challenge is not equivalent to every chronic inflammatory condition. Evidence access: Primary full text NAD+ flux is maintained in aged mice despite lower tissue concentrations. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34559996/ · DOI 10.1016/j.cels.2021.09.001
Complete structured claim and evidence
HMGA1-dependent NAMPT expression contributed to increased NAD metabolism and the proinflammatory secretory phenotype in oncogene-induced senescent human IMR90 fibroblasts.
Human HMGA1 → Human nicotinamide phosphoribosyltransferase / NAMPT source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human fibroblast oncogene-induced senescence with genetic perturbations.
limitations
Senescence type matters; replicative and mitochondrial-dysfunction senescence need not share this pattern.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
A gene regulator can increase NAD salvage in a cell that is already senescent.
primary_references
NAD+ metabolism governs the proinflammatory senescence-associated secretome. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30778219/ · DOI 10.1038/s41556-019-0287-4
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 148–154
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human fibroblast oncogene-induced senescence with genetic perturbations. · source_derived_draft · unverified_draft
## nad-plus-hmga-nampt A gene regulator can increase NAD salvage in a cell that is already senescent. HMGA1-dependent NAMPT expression contributed to increased NAD metabolism and the proinflammatory secretory phenotype in oncogene-induced senescent human IMR90 fibroblasts. Model: Human fibroblast oncogene-induced senescence with genetic perturbations. Limitations: Senescence type matters; replicative and mitochondrial-dysfunction senescence need not share this pattern. Evidence access: Primary full text NAD+ metabolism governs the proinflammatory senescence-associated secretome. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30778219/ · DOI 10.1038/s41556-019-0287-4
Complete structured claim and evidence
NAMPT-supported NAD metabolism sustained glycolysis and respiration and promoted a proinflammatory SASP through the AMPK–p53–p38/NF-kappaB regulatory network in the tested senescent cells.
Human nicotinamide phosphoribosyltransferase / NAMPT → Proinflammatory SASP in human IMR90 fibroblasts source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human IMR90 fibroblast senescence; NAMPT inhibition and knockdown.
limitations
Not proof that NAD supplementation causes cancer in humans or that all senescent cells respond alike.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Supporting cellular metabolism can also support inflammatory secretion.
primary_references
NAD+ metabolism governs the proinflammatory senescence-associated secretome. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30778219/ · DOI 10.1038/s41556-019-0287-4
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 156–162
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human IMR90 fibroblast senescence; NAMPT inhibition and knockdown. · source_derived_draft · unverified_draft
## nad-plus-nampt-sasp Supporting cellular metabolism can also support inflammatory secretion. NAMPT-supported NAD metabolism sustained glycolysis and respiration and promoted a proinflammatory SASP through the AMPK–p53–p38/NF-kappaB regulatory network in the tested senescent cells. Model: Human IMR90 fibroblast senescence; NAMPT inhibition and knockdown. Limitations: Not proof that NAD supplementation causes cancer in humans or that all senescent cells respond alike. Evidence access: Primary full text NAD+ metabolism governs the proinflammatory senescence-associated secretome. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30778219/ · DOI 10.1038/s41556-019-0287-4
Complete structured claim and evidence
Bacterial PncA converted nicotinamide to nicotinic acid, enabling an alternative deamidated NAD synthesis route in mammalian cells.
Escherichia coli nicotinamidase PncA → Nicotinic acid source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
E. coli PncA genetic experiments, mammalian cancer cells and xenografts.
limitations
PncA is bacterial; do not create a human nicotinamidase from this result.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Microbes can redirect one vitamin form into another route around a blocked enzyme.
primary_references
Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32130883/ · DOI 10.1016/j.cmet.2020.02.001
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 164–170
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · E. coli PncA genetic experiments, mammalian cancer cells and xenografts. · source_derived_draft · unverified_draft
## nad-plus-microbial-deamidation Microbes can redirect one vitamin form into another route around a blocked enzyme. Bacterial PncA converted nicotinamide to nicotinic acid, enabling an alternative deamidated NAD synthesis route in mammalian cells. Model: E. coli PncA genetic experiments, mammalian cancer cells and xenografts. Limitations: PncA is bacterial; do not create a human nicotinamidase from this result. Evidence access: Primary full text Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32130883/ · DOI 10.1016/j.cmet.2020.02.001
Complete structured claim and evidence
Removing bacterial PncA abolished, and supplying it enabled, bacterial protection against NAMPT inhibitors in the tested cancer-cell and xenograft systems.
Escherichia coli nicotinamidase PncA → NAMPT-inhibitor-induced cancer-cell killing source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Microbial genetic manipulation plus mammalian cancer models.
limitations
Preclinical resistance mechanism, not guidance to manipulate microbiota during cancer treatment.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
An alternative precursor source can defeat a blockade of salvage.
primary_references
Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32130883/ · DOI 10.1016/j.cmet.2020.02.001
trigger_kind
machinery_impairment Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 172–178
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Microbial genetic manipulation plus mammalian cancer models. · source_derived_draft · unverified_draft
## nad-plus-microbial-rescue An alternative precursor source can defeat a blockade of salvage. Removing bacterial PncA abolished, and supplying it enabled, bacterial protection against NAMPT inhibitors in the tested cancer-cell and xenograft systems. Model: Microbial genetic manipulation plus mammalian cancer models. Limitations: Preclinical resistance mechanism, not guidance to manipulate microbiota during cancer treatment. Evidence access: Primary full text Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32130883/ · DOI 10.1016/j.cmet.2020.02.001
Complete structured claim and evidence
Stable-isotope tracing and microbiota depletion showed bacterial deamidation contributed substantially to tissue NAD increases after oral nicotinamide or NR in mice.
Microbiota-mediated NAD precursor deamidation in mice → Mouse tissue NAD response to oral precursors source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse isotope tracing and microbiota-depletion experiments.
limitations
Not a measured human conversion fraction or proof that all formulations use the same route.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
An oral precursor may reach tissues through a microbially altered route.
primary_references
Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32130883/ · DOI 10.1016/j.cmet.2020.02.001
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 180–186
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse isotope tracing and microbiota-depletion experiments. · source_derived_draft · unverified_draft
## nad-plus-microbiota-oral-precursors An oral precursor may reach tissues through a microbially altered route. Stable-isotope tracing and microbiota depletion showed bacterial deamidation contributed substantially to tissue NAD increases after oral nicotinamide or NR in mice. Model: Mouse isotope tracing and microbiota-depletion experiments. Limitations: Not a measured human conversion fraction or proof that all formulations use the same route. Evidence access: Primary full text Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32130883/ · DOI 10.1016/j.cmet.2020.02.001
Complete structured claim and evidence
Mouse tracer experiments identified liver conversion of tryptophan to NAD followed by nicotinamide release to support other tissues.
Mouse liver tryptophan-to-NAD flux → Nicotinamide source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse circulating/tissue stable-isotope flux measurements.
limitations
Does not imply that all tissues lack de novo synthesis or that liver is the only contributor under every condition.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
One organ can help supply another with recycled vitamin material.
primary_references
Quantitative Analysis of NAD Synthesis-Breakdown Fluxes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29685734/ · DOI 10.1016/j.cmet.2018.03.018
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 188–194
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse circulating/tissue stable-isotope flux measurements. · source_derived_draft · unverified_draft
## nad-plus-liver-nam-export One organ can help supply another with recycled vitamin material. Mouse tracer experiments identified liver conversion of tryptophan to NAD followed by nicotinamide release to support other tissues. Model: Mouse circulating/tissue stable-isotope flux measurements. Limitations: Does not imply that all tissues lack de novo synthesis or that liver is the only contributor under every condition. Evidence access: Primary full text Quantitative Analysis of NAD Synthesis-Breakdown Fluxes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29685734/ · DOI 10.1016/j.cmet.2018.03.018
Complete structured claim and evidence
In mouse tracer experiments, oral NR and NMN were largely metabolized to nicotinamide, whereas intravenous administration delivered intact precursors to multiple tissues.
Nicotinamide riboside → Nicotinamide source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse oral versus intravenous isotope-labeled precursor administration.
limitations
This study tests NR/NMN, not intact NAD infusion; it does not establish an optimal human route.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Route of administration changes which molecules tissues encounter.
primary_references
Quantitative Analysis of NAD Synthesis-Breakdown Fluxes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29685734/ · DOI 10.1016/j.cmet.2018.03.018
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 196–202
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse oral versus intravenous isotope-labeled precursor administration. · source_derived_draft · unverified_draft
## nad-plus-oral-versus-iv-precursors Route of administration changes which molecules tissues encounter. In mouse tracer experiments, oral NR and NMN were largely metabolized to nicotinamide, whereas intravenous administration delivered intact precursors to multiple tissues. Model: Mouse oral versus intravenous isotope-labeled precursor administration. Limitations: This study tests NR/NMN, not intact NAD infusion; it does not establish an optimal human route. Evidence access: Primary full text Quantitative Analysis of NAD Synthesis-Breakdown Fluxes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29685734/ · DOI 10.1016/j.cmet.2018.03.018
Complete structured claim and evidence
Respiration-deficient proliferating cells became limited in aspartate synthesis; alpha-ketobutyrate restored proliferation as an electron acceptor without supplying carbon or ATP.
Respiration-deficient proliferating cell models → L-Aspartate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Cultured proliferating mammalian cells with impaired respiration.
limitations
ATP is not generally dispensable; this experiment isolates an electron-acceptor bottleneck in supplied culture conditions.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Respiration supports building material by restoring electron acceptors, as well as producing ATP.
primary_references
Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232225/ · DOI 10.1016/j.cell.2015.07.017
trigger_kind
machinery_impairment Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 204–210
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured proliferating mammalian cells with impaired respiration. · source_derived_draft · unverified_draft
## nad-plus-electron-acceptor-aspartate Respiration supports building material by restoring electron acceptors, as well as producing ATP. Respiration-deficient proliferating cells became limited in aspartate synthesis; alpha-ketobutyrate restored proliferation as an electron acceptor without supplying carbon or ATP. Model: Cultured proliferating mammalian cells with impaired respiration. Limitations: ATP is not generally dispensable; this experiment isolates an electron-acceptor bottleneck in supplied culture conditions. Evidence access: Primary full text Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232225/ · DOI 10.1016/j.cell.2015.07.017
Complete structured claim and evidence
Aspartate supplementation rescued proliferation of the tested respiration-deficient cells.
L-Aspartate → Proliferation of respiration-deficient cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mammalian cell-culture respiration perturbation and rescue.
limitations
Cell-culture rescue does not establish oral aspartate delivery or therapeutic efficacy in people.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Supplying the missing product can bypass a biosynthetic bottleneck.
primary_references
Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232225/ · DOI 10.1016/j.cell.2015.07.017
trigger_kind
machinery_impairment Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 212–218
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mammalian cell-culture respiration perturbation and rescue. · source_derived_draft · unverified_draft
## nad-plus-aspartate-rescue Supplying the missing product can bypass a biosynthetic bottleneck. Aspartate supplementation rescued proliferation of the tested respiration-deficient cells. Model: Mammalian cell-culture respiration perturbation and rescue. Limitations: Cell-culture rescue does not establish oral aspartate delivery or therapeutic efficacy in people. Evidence access: Primary full text Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232225/ · DOI 10.1016/j.cell.2015.07.017
Complete structured claim and evidence
Pyruvate supplied an alternative electron-acceptor route for NAD+ regeneration and aspartate synthesis, reducing the antiproliferative effect of metformin in the tested cancer cells.
Pyruvate → NAD regeneration in metformin-treated cancer cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Cancer-cell culture, complex-I-dependent respiration and nutrient manipulation.
limitations
Experimental concentrations and culture composition matter; not a medication adjustment or claim that metformin has one mechanism in all tissues.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Available nutrients can change the effect of an inhibitor on the same pathway.
primary_references
Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 220–226
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cancer-cell culture, complex-I-dependent respiration and nutrient manipulation. · source_derived_draft · unverified_draft
## nad-plus-pyruvate-metformin Available nutrients can change the effect of an inhibitor on the same pathway. Pyruvate supplied an alternative electron-acceptor route for NAD+ regeneration and aspartate synthesis, reducing the antiproliferative effect of metformin in the tested cancer cells. Model: Cancer-cell culture, complex-I-dependent respiration and nutrient manipulation. Limitations: Experimental concentrations and culture composition matter; not a medication adjustment or claim that metformin has one mechanism in all tissues. Evidence access: Primary full text Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006
Complete structured claim and evidence
CD73 silencing or pharmacological inhibition reduced NMN-supported survival after NAMPT inhibition in human tumor cells; the authors assigned CD73 a role in converting extracellular NMN to NR.
Human ecto-5-prime-nucleotidase / CD73 / NT5E → Nicotinamide riboside source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human tumor-cell CD73 overexpression/silencing and FK866 experiments.
limitations
Mechanistic assignment is disputed by the later human recombinant-enzyme and knockout study. Primary abstract accessed here; direct catalytic attribution is retained as reported.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
One study found that CD73 helped cells use an outside NAD precursor.
primary_references
CD73 protein as a source of extracellular precursors for sustained NAD+ biosynthesis in FK866-treated tumor cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23880765/ · DOI 10.1074/jbc.M113.470435
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 228–234
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human tumor-cell CD73 overexpression/silencing and FK866 experiments. · source_derived_draft · unverified_draft
## nad-plus-cd73-positive One study found that CD73 helped cells use an outside NAD precursor. CD73 silencing or pharmacological inhibition reduced NMN-supported survival after NAMPT inhibition in human tumor cells; the authors assigned CD73 a role in converting extracellular NMN to NR. Model: Human tumor-cell CD73 overexpression/silencing and FK866 experiments. Limitations: Mechanistic assignment is disputed by the later human recombinant-enzyme and knockout study. Primary abstract accessed here; direct catalytic attribution is retained as reported. Evidence access: Primary abstract CD73 protein as a source of extracellular precursors for sustained NAD+ biosynthesis in FK866-treated tumor cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23880765/ · DOI 10.1074/jbc.M113.470435
Complete structured claim and evidence
Recombinant human CD73 did not process NAD+ and processed NMN poorly in the reported biochemical assays.
Human ecto-5-prime-nucleotidase / CD73 / NT5E → NMN source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human recombinant enzyme; biochemical substrate assays.
limitations
Do not erase the earlier cellular result. Preparation, assay sensitivity and indirect cellular effects require reconciliation.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
A later direct assay challenged the proposed precursor-processing enzyme.
primary_references
Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 236–242
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant enzyme; biochemical substrate assays. · source_derived_draft · unverified_draft
## nad-plus-cd73-negative A later direct assay challenged the proposed precursor-processing enzyme. Recombinant human CD73 did not process NAD+ and processed NMN poorly in the reported biochemical assays. Model: Human recombinant enzyme; biochemical substrate assays. Limitations: Do not erase the earlier cellular result. Preparation, assay sensitivity and indirect cellular effects require reconciliation. Evidence access: Primary full text Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9
Complete structured claim and evidence
CD73 knockout did not prevent human cancer cells from using extracellular NAD+ or NMN to restore intracellular NAD+ under the tested conditions.
Human ecto-5-prime-nucleotidase / CD73 / NT5E → Intracellular NAD restoration from extracellular precursors in human cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human cancer-cell CRISPR knockout and precursor supplementation.
limitations
Does not identify a universal alternative uptake route or prove intact NAD crossed the plasma membrane.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Cells could still use outside precursor material without CD73.
primary_references
Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 244–250
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell CRISPR knockout and precursor supplementation. · source_derived_draft · unverified_draft
## nad-plus-cd73-knockout Cells could still use outside precursor material without CD73. CD73 knockout did not prevent human cancer cells from using extracellular NAD+ or NMN to restore intracellular NAD+ under the tested conditions. Model: Human cancer-cell CRISPR knockout and precursor supplementation. Limitations: Does not identify a universal alternative uptake route or prove intact NAD crossed the plasma membrane. Evidence access: Primary full text Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9
Complete structured claim and evidence
FK866-mediated NAD depletion impaired DNA repair and damage-induced PARylation in the tested human cancer-cell experiments.
Human nicotinamide phosphoribosyltransferase / NAMPT → DNA repair after NAD depletion in human MCF-7 cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human MCF-7 cells, NAMPT inhibitor, genotoxins and CometChip/PAR assays.
limitations
Genotoxin and endpoint dependent; not proof that raising NAD prevents human cancer.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
When salvage is blocked, repair enzymes can lose access to their substrate.
primary_references
Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9
trigger_kind
machinery_impairment Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 252–258
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MCF-7 cells, NAMPT inhibitor, genotoxins and CometChip/PAR assays. · source_derived_draft · unverified_draft
## nad-plus-repair-depletion When salvage is blocked, repair enzymes can lose access to their substrate. FK866-mediated NAD depletion impaired DNA repair and damage-induced PARylation in the tested human cancer-cell experiments. Model: Human MCF-7 cells, NAMPT inhibitor, genotoxins and CometChip/PAR assays. Limitations: Genotoxin and endpoint dependent; not proof that raising NAD prevents human cancer. Evidence access: Primary full text Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9
Complete structured claim and evidence
Extracellular NAD+ or NMN restored intracellular NAD availability, PAR-dependent signaling and XRCC1 recruitment in the tested NAD-depleted human cells independently of CD73 status.
NAD+ → NAD-dependent XRCC1 recruitment and PAR signaling in human cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human MCF-7 cells with NAMPT inhibition, CD73 comparison and serum-containing medium; NMN/NR XRCC1 rescue is reported as data not shown.
limitations
Rescue depended on medium and incubation time; serum-free and heat-inactivated-serum conditions did not give the same early rescue. No proof of intact cellular NAD uptake or clinical benefit.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Supplying precursor material restored part of a repair response in this model.
primary_references
Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 260–266
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MCF-7 cells with NAMPT inhibition, CD73 comparison and serum-containing medium; NMN/NR XRCC1 rescue is reported as data not shown. · source_derived_draft · unverified_draft
## nad-plus-repair-precursor-rescue Supplying precursor material restored part of a repair response in this model. Extracellular NAD+ or NMN restored intracellular NAD availability, PAR-dependent signaling and XRCC1 recruitment in the tested NAD-depleted human cells independently of CD73 status. Model: Human MCF-7 cells with NAMPT inhibition, CD73 comparison and serum-containing medium; NMN/NR XRCC1 rescue is reported as data not shown. Limitations: Rescue depended on medium and incubation time; serum-free and heat-inactivated-serum conditions did not give the same early rescue. No proof of intact cellular NAD uptake or clinical benefit. Evidence access: Primary full text Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9
Complete structured claim and evidence
Extracellular NAD supported ART2.2-dependent ADP-ribosylation and activation of P2X7 in mouse regulatory T cells.
Mouse ADP-ribosyltransferase ARTC2.2 / Art2b → Mouse purinergic receptor P2X7 / P2rx7 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse regulatory T-cell experiments with ART2.2 blockade.
limitations
Mouse pathway; not a demonstrated human IV-NAD mechanism or toxicity threshold.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Outside the cell, NAD can act as a signaling substrate rather than an energy supplement.
primary_references
Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20975043/ · DOI 10.1084/jem.20091154
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 268–274
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse regulatory T-cell experiments with ART2.2 blockade. · source_derived_draft · unverified_draft
## nad-plus-extracellular-art2 Outside the cell, NAD can act as a signaling substrate rather than an energy supplement. Extracellular NAD supported ART2.2-dependent ADP-ribosylation and activation of P2X7 in mouse regulatory T cells. Model: Mouse regulatory T-cell experiments with ART2.2 blockade. Limitations: Mouse pathway; not a demonstrated human IV-NAD mechanism or toxicity threshold. Evidence access: Primary full text Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20975043/ · DOI 10.1084/jem.20091154
Complete structured claim and evidence
NAD administration depleted mouse regulatory T cells through the ART2.2/P2X7 pathway; ART2.2-blocking antibody protected against the effect.
Mouse purinergic receptor P2X7 / P2rx7 → NAD-induced mouse regulatory T-cell death source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse in-vitro and in-vivo NAD intervention.
limitations
Species and exposure dependent; cannot be directly assigned to human regulatory T cells.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
A receptor-linked extracellular reaction can determine which immune cells survive.
primary_references
Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20975043/ · DOI 10.1084/jem.20091154
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 276–282
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse in-vitro and in-vivo NAD intervention. · source_derived_draft · unverified_draft
## nad-plus-treg-death A receptor-linked extracellular reaction can determine which immune cells survive. NAD administration depleted mouse regulatory T cells through the ART2.2/P2X7 pathway; ART2.2-blocking antibody protected against the effect. Model: Mouse in-vitro and in-vivo NAD intervention. Limitations: Species and exposure dependent; cannot be directly assigned to human regulatory T cells. Evidence access: Primary full text Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20975043/ · DOI 10.1084/jem.20091154
Complete structured claim and evidence
In a randomized pilot with eight NAD+ recipients and three saline controls, 750 mg NAD+ over six hours produced a significant plasma NAD increase at the six-hour endpoint, with no significant early rise during the first two hours.
Intravenous NAD+ intervention in humans → Human plasma NAD concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human pilot; approximately 3 micromoles/minute; serial plasma and urine sampling.
limitations
Small pharmacokinetic study; disappearance from plasma does not prove intact tissue uptake or clinical benefit.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Infusion input and measured blood concentration need not rise together immediately.
primary_references
A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31572171/ · DOI 10.3389/fnagi.2019.00257
trigger_kind
biomarker_context Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 284–290
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human pilot; approximately 3 micromoles/minute; serial plasma and urine sampling. · source_derived_draft · unverified_draft
## nad-plus-iv-plasma Infusion input and measured blood concentration need not rise together immediately. In a randomized pilot with eight NAD+ recipients and three saline controls, 750 mg NAD+ over six hours produced a significant plasma NAD increase at the six-hour endpoint, with no significant early rise during the first two hours. Model: Human pilot; approximately 3 micromoles/minute; serial plasma and urine sampling. Limitations: Small pharmacokinetic study; disappearance from plasma does not prove intact tissue uptake or clinical benefit. Evidence access: Primary full text A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31572171/ · DOI 10.3389/fnagi.2019.00257
Complete structured claim and evidence
The six-hour NAD+ infusion altered circulating breakdown products and urinary NAD/metabolite excretion, demonstrating substantial handling of administered material.
Intravenous NAD+ intervention in humans → Human NAD metabolites after intravenous NAD source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Same 11-person human pilot.
limitations
Not a quantitative map of every tissue uptake route or evidence of rejuvenation.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Some infused material is broken down or excreted.
primary_references
A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31572171/ · DOI 10.3389/fnagi.2019.00257
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 292–298
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same 11-person human pilot. · source_derived_draft · unverified_draft
## nad-plus-iv-metabolites Some infused material is broken down or excreted. The six-hour NAD+ infusion altered circulating breakdown products and urinary NAD/metabolite excretion, demonstrating substantial handling of administered material. Model: Same 11-person human pilot. Limitations: Not a quantitative map of every tissue uptake route or evidence of rejuvenation. Evidence access: Primary full text A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31572171/ · DOI 10.3389/fnagi.2019.00257
Complete structured claim and evidence
A retrospective commercial-clinic series compared six clients receiving 500 mg IV NAD+ with eight receiving 500 mg IV NR over four-day loading protocols; NAD recipients reported gastrointestinal symptoms, chest pressure or elevated heart rate and required longer infusions.
Intravenous NAD+ intervention in humans → Symptoms during commercial IV NAD infusions source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Small nonrandomized retrospective clinical series.
limitations
Selection, infusion rate and clinic practices limit causal comparison; not efficacy evidence or an incidence estimate for all users.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Infusion tolerability is a separate question from whether NAD biomarkers rise.
primary_references
Intravenous infusion of nicotinamide adenine dinucleotide (NAD+) versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41704678/ · DOI 10.3389/fragi.2026.1652582
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 300–306
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Small nonrandomized retrospective clinical series. · source_derived_draft · unverified_draft
## nad-plus-iv-tolerability Infusion tolerability is a separate question from whether NAD biomarkers rise. A retrospective commercial-clinic series compared six clients receiving 500 mg IV NAD+ with eight receiving 500 mg IV NR over four-day loading protocols; NAD recipients reported gastrointestinal symptoms, chest pressure or elevated heart rate and required longer infusions. Model: Small nonrandomized retrospective clinical series. Limitations: Selection, infusion rate and clinic practices limit causal comparison; not efficacy evidence or an incidence estimate for all users. Evidence access: Primary full text Intravenous infusion of nicotinamide adenine dinucleotide (NAD+) versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41704678/ · DOI 10.3389/fragi.2026.1652582
Complete structured claim and evidence
A five-day placebo-controlled trial of oral LNAD+ reported whole-blood intracellular NAD 53% higher versus placebo at day six; 60 adults were randomized and 50 entered the primary analysis.
LathMized NAD+ formulation → Whole-blood intracellular NAD measurement source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Healthy adults aged 45–75; short phase 0/1b trial, NCT07336836, retrospectively registered.
limitations
Primary abstract only. Formulation-specific, no isotope-traced intact uptake, no inference about muscle or brain NAD; exclusions and assay details require full-report appraisal.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
A particular oral formulation increased a blood-cell-associated NAD measure.
primary_references
Oral LNAD+ rapidly elevates whole blood intracellular NAD and metabolic flux without elevating plasma NAD: evidence from a randomized controlled trial. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42530810/ · DOI 10.1007/s11357-026-02399-1
trigger_kind
biomarker_context Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 308–314
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Healthy adults aged 45–75; short phase 0/1b trial, NCT07336836, retrospectively registered. · source_derived_draft · unverified_draft
## nad-plus-oral-formulation-blood A particular oral formulation increased a blood-cell-associated NAD measure. A five-day placebo-controlled trial of oral LNAD+ reported whole-blood intracellular NAD 53% higher versus placebo at day six; 60 adults were randomized and 50 entered the primary analysis. Model: Healthy adults aged 45–75; short phase 0/1b trial, NCT07336836, retrospectively registered. Limitations: Primary abstract only. Formulation-specific, no isotope-traced intact uptake, no inference about muscle or brain NAD; exclusions and assay details require full-report appraisal. Evidence access: Primary abstract Oral LNAD+ rapidly elevates whole blood intracellular NAD and metabolic flux without elevating plasma NAD: evidence from a randomized controlled trial. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42530810/ · DOI 10.1007/s11357-026-02399-1
Complete structured claim and evidence
The same LNAD+ trial found unchanged plasma NAD while methyl-nicotinamide and 2PY increased.
LathMized NAD+ formulation → Human plasma NAD concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Same five-day randomized trial; primary analysis n=50.
limitations
Catabolite concentration changes are consistent with metabolism but are not direct quantitative flux measurements or proof of intact uptake.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Blood compartments and breakdown products can move differently.
primary_references
Oral LNAD+ rapidly elevates whole blood intracellular NAD and metabolic flux without elevating plasma NAD: evidence from a randomized controlled trial. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42530810/ · DOI 10.1007/s11357-026-02399-1
trigger_kind
biomarker_context Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 316–322
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same five-day randomized trial; primary analysis n=50. · source_derived_draft · unverified_draft
## nad-plus-oral-formulation-plasma Blood compartments and breakdown products can move differently. The same LNAD+ trial found unchanged plasma NAD while methyl-nicotinamide and 2PY increased. Model: Same five-day randomized trial; primary analysis n=50. Limitations: Catabolite concentration changes are consistent with metabolism but are not direct quantitative flux measurements or proof of intact uptake. Evidence access: Primary abstract Oral LNAD+ rapidly elevates whole blood intracellular NAD and metabolic flux without elevating plasma NAD: evidence from a randomized controlled trial. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42530810/ · DOI 10.1007/s11357-026-02399-1
Complete structured claim and evidence
No secondary clinical, vital-sign, wellbeing or wearable-derived endpoint survived multiplicity correction in the LNAD+ trial; one mild nausea event occurred in the active arm.
LathMized NAD+ formulation → Short-term clinical endpoints in the LNAD trial source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same short trial; exploratory secondary outcomes.
limitations
Five days cannot establish long-term safety, longevity or disease prevention. Retrospective registration and industry-affiliated authors remain visible in the reference record.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
A large biomarker change did not establish a clinical benefit.
primary_references
Oral LNAD+ rapidly elevates whole blood intracellular NAD and metabolic flux without elevating plasma NAD: evidence from a randomized controlled trial. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42530810/ · DOI 10.1007/s11357-026-02399-1
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 324–330
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same short trial; exploratory secondary outcomes. · source_derived_draft · unverified_draft
## nad-plus-oral-formulation-clinical-null A large biomarker change did not establish a clinical benefit. No secondary clinical, vital-sign, wellbeing or wearable-derived endpoint survived multiplicity correction in the LNAD+ trial; one mild nausea event occurred in the active arm. Model: Same short trial; exploratory secondary outcomes. Limitations: Five days cannot establish long-term safety, longevity or disease prevention. Retrospective registration and industry-affiliated authors remain visible in the reference record. Evidence access: Primary abstract Oral LNAD+ rapidly elevates whole blood intracellular NAD and metabolic flux without elevating plasma NAD: evidence from a randomized controlled trial. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42530810/ · DOI 10.1007/s11357-026-02399-1
Complete structured claim and evidence
In 25 postmenopausal women with prediabetes and overweight/obesity, 250 mg/day NMN for ten weeks increased basal PBMC NAD but did not increase measured muscle NAD; muscle NAD-related catabolites increased.
NMN → Skeletal muscle NAD+ content source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Randomized double-blind trial; 13 NMN and 12 placebo; biopsies and metabolomics.
limitations
Catabolites suggest turnover but are not isotope-measured flux; total biopsy NAD can miss small subcellular pools.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
A blood-cell response did not mean measured muscle NAD rose.
primary_references
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888596/ · DOI 10.1126/science.abe9985
trigger_kind
biomarker_context Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 332–338
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized double-blind trial; 13 NMN and 12 placebo; biopsies and metabolomics. · source_derived_draft · unverified_draft
## nad-plus-nmn-muscle-versus-blood A blood-cell response did not mean measured muscle NAD rose. In 25 postmenopausal women with prediabetes and overweight/obesity, 250 mg/day NMN for ten weeks increased basal PBMC NAD but did not increase measured muscle NAD; muscle NAD-related catabolites increased. Model: Randomized double-blind trial; 13 NMN and 12 placebo; biopsies and metabolomics. Limitations: Catabolites suggest turnover but are not isotope-measured flux; total biopsy NAD can miss small subcellular pools. Evidence access: Primary full text Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888596/ · DOI 10.1126/science.abe9985
Complete structured claim and evidence
The same NMN trial increased insulin-stimulated glucose disposal and muscle insulin signaling relative to baseline, while placebo did not; the study did not demonstrate broad improvement in all metabolic endpoints.
NMN → Clamp-measured muscle insulin sensitivity after NMN source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Ten-week randomized trial in postmenopausal women with prediabetes; clamp and muscle signaling measurements.
limitations
Small defined population, not proof of longevity, benefit in healthy adults or a proven NAD mediator.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
A specific physiological improvement can occur without a measured rise in total muscle NAD.
primary_references
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888596/ · DOI 10.1126/science.abe9985
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 340–346
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Ten-week randomized trial in postmenopausal women with prediabetes; clamp and muscle signaling measurements. · source_derived_draft · unverified_draft
## nad-plus-nmn-clamp A specific physiological improvement can occur without a measured rise in total muscle NAD. The same NMN trial increased insulin-stimulated glucose disposal and muscle insulin signaling relative to baseline, while placebo did not; the study did not demonstrate broad improvement in all metabolic endpoints. Model: Ten-week randomized trial in postmenopausal women with prediabetes; clamp and muscle signaling measurements. Limitations: Small defined population, not proof of longevity, benefit in healthy adults or a proven NAD mediator. Evidence access: Primary full text Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888596/ · DOI 10.1126/science.abe9985
Complete structured claim and evidence
In the tested human A549 and HeLa cancer cells, net pyruvate-to-lactate conversion provided an alternative route to regenerate NAD+ from NADH during complex-I inhibition.
Human lactate dehydrogenase activity → NAD+ source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human cancer-cell nutrient manipulation and NAD+/NADH measurements.
limitations
Reaction-level LDH activity is recorded without assigning an untested isoform.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
An electron acceptor can restore NAD without making new NAD molecules.
primary_references
Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 348–354
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell nutrient manipulation and NAD+/NADH measurements. · source_derived_draft · unverified_draft
## nad-plus-ldh-redox An electron acceptor can restore NAD without making new NAD molecules. In the tested human A549 and HeLa cancer cells, net pyruvate-to-lactate conversion provided an alternative route to regenerate NAD+ from NADH during complex-I inhibition. Model: Human cancer-cell nutrient manipulation and NAD+/NADH measurements. Limitations: Reaction-level LDH activity is recorded without assigning an untested isoform. Evidence access: Primary full text Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006
Complete structured claim and evidence
The LDH inhibitor GSK2837808A partially inhibited pyruvate-to-lactate conversion and restored metformin sensitivity in pyruvate-containing cancer-cell medium.
Human lactate dehydrogenase activity → Pyruvate-associated metformin resistance in human cancer cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human cancer-cell pharmacological inhibition and proliferation assay.
limitations
Inhibitor results do not resolve individual LDH isoforms or establish a clinical combination.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Blocking the backup redox route removes its rescue effect.
primary_references
Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006
trigger_kind
machinery_impairment Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 356–362
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell pharmacological inhibition and proliferation assay. · source_derived_draft · unverified_draft
## nad-plus-ldh-inhibition Blocking the backup redox route removes its rescue effect. The LDH inhibitor GSK2837808A partially inhibited pyruvate-to-lactate conversion and restored metformin sensitivity in pyruvate-containing cancer-cell medium. Model: Human cancer-cell pharmacological inhibition and proliferation assay. Limitations: Inhibitor results do not resolve individual LDH isoforms or establish a clinical combination. Evidence access: Primary full text Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006
Complete structured claim and evidence
NAD+ restored XRCC1 recruitment in NAD-depleted MCF-7 cells more readily in fetal-bovine-serum-containing medium than serum-free or heat-inactivated-serum conditions; precursor metabolism and rescue also depended on incubation time.
NAD precursor processing by fetal bovine serum → NAD-dependent XRCC1 recruitment and PAR signaling in human cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human cells; medium comparison, NMR precursor stability and six- versus 24-hour exposure.
limitations
Serum components are not individually identified by this result; do not assign the effect to human CD73 or infer direct uptake.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
The material outside a cell can determine whether an added precursor works.
primary_references
Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 364–370
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cells; medium comparison, NMR precursor stability and six- versus 24-hour exposure. · source_derived_draft · unverified_draft
## nad-plus-serum-processing The material outside a cell can determine whether an added precursor works. NAD+ restored XRCC1 recruitment in NAD-depleted MCF-7 cells more readily in fetal-bovine-serum-containing medium than serum-free or heat-inactivated-serum conditions; precursor metabolism and rescue also depended on incubation time. Model: Human cells; medium comparison, NMR precursor stability and six- versus 24-hour exposure. Limitations: Serum components are not individually identified by this result; do not assign the effect to human CD73 or infer direct uptake. Evidence access: Primary full text Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9
Complete structured claim and evidence
Human NAMPT converts nicotinamide and PRPP to nicotinamide mononucleotide and pyrophosphate.
Human nicotinamide phosphoribosyltransferase / NAMPT → NMN source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/nampt2009.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1272, "file_sha256": "b67ca4decafccfc4132deba87ffddf2114e60542c77fa4354165d414aa0f13c5", "text_sha256": "b67ca4decafccfc4132deba87ffddf2114e60542c77fa4354165d414aa0f13c5"}
experimental_model
Purified human NAMPT reaction monitoring by 1H/31P NMR and substrate/product crystallography
exposure
Biochemical or structural assay; no dietary intervention
limitations
Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Nicotinamide salvage first makes NMN.
primary_references
[b3-pre-nampt2009] Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase. (2010). https://pubmed.ncbi.nlm.nih.gov/19819904/ DOI: 10.1093/jb/mvp152
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 369–380
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human NAMPT reaction monitoring by 1H/31P NMR and substrate/product crystallography · source_derived_draft · unverified_draft
### b3-pre-nampt-reaction Human NAMPT converts nicotinamide and PRPP to nicotinamide mononucleotide and pyrophosphate. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotinamide salvage first makes NMN. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human NAMPT reaction monitoring by 1H/31P NMR and substrate/product crystallography limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nampt2009.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1272, "file_sha256": "b67ca4decafccfc4132deba87ffddf2114e60542c77fa4354165d414aa0f13c5", "text_sha256": "b67ca4decafccfc4132deba87ffddf2114e60542c77fa4354165d414aa0f13c5"} [b3-pre-nampt2009] Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase. (2010). https://pubmed.ncbi.nlm.nih.gov/19819904/ DOI: 10.1093/jb/mvp152
Complete structured claim and evidence
Human NAPRT catalyzes phosphoribosyl transfer from PRPP to nicotinic acid, producing nicotinic acid mononucleotide and pyrophosphate.
Human nicotinate phosphoribosyltransferase / NAPRT → Nicotinic acid mononucleotide source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/naprt2015.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1606, "file_sha256": "df6e36cf3464d4cda171d06ee24065532dee0d8b5fd5c3ccafcb1cc8df951bbe", "text_sha256": "df6e36cf3464d4cda171d06ee24065532dee0d8b5fd5c3ccafcb1cc8df951bbe"}
experimental_model
Recombinant human NAPRT crystallography and docking; purified protein, no intact tissue
exposure
Biochemical or structural assay; no dietary intervention
limitations
Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Nicotinic acid enters its NAD-building route through NAPRT.
primary_references
[b3-pre-naprt2015] Crystal structure of human nicotinic acid phosphoribosyltransferase. (2015). https://pubmed.ncbi.nlm.nih.gov/26042198/ DOI: 10.1016/j.fob.2015.05.002
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 249–260
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human NAPRT crystallography and docking; purified protein, no intact tissue · source_derived_draft · unverified_draft
### b3-pre-naprt-reaction Human NAPRT catalyzes phosphoribosyl transfer from PRPP to nicotinic acid, producing nicotinic acid mononucleotide and pyrophosphate. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotinic acid enters its NAD-building route through NAPRT. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human NAPRT crystallography and docking; purified protein, no intact tissue limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/naprt2015.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1606, "file_sha256": "df6e36cf3464d4cda171d06ee24065532dee0d8b5fd5c3ccafcb1cc8df951bbe", "text_sha256": "df6e36cf3464d4cda171d06ee24065532dee0d8b5fd5c3ccafcb1cc8df951bbe"} [b3-pre-naprt2015] Crystal structure of human nicotinic acid phosphoribosyltransferase. (2015). https://pubmed.ncbi.nlm.nih.gov/26042198/ DOI: 10.1016/j.fob.2015.05.002
Complete structured claim and evidence
Inorganic phosphate activated purified recombinant human NAPRT in the reported kinetic experiments.
Inorganic phosphate → Human nicotinate phosphoribosyltransferase / NAPRT source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Phosphorus-containing inorganic phosphate alters a niacin precursor enzyme in vitro; no dietary phosphate deficiency was tested.
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/naprt2011.abstract.txt", "locator": "Indexed primary abstract; identified exact passage", "start_char": 815, "end_char": 876, "file_sha256": "c9f4959ad65f0b0621179b3ccf00c460f7f648293bf910209ecc6e7785417deb", "text_sha256": "53af728f32d65092c92246c77801e92e521892adac900df62bf3f8206129f714"}
experimental_model
Purified recombinant human NAPRT kinetic assays and site-directed mutagenesis
exposure
Biochemical or structural assay; no dietary intervention
limitations
Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Phosphate supported this isolated precursor enzyme.
primary_references
[b3-pre-naprt2011] Characterization of human nicotinate phosphoribosyltransferase: Kinetic studies, structure prediction and functional analysis by site-directed mutagenesis. (2012). https://pubmed.ncbi.nlm.nih.gov/21742010/ DOI: 10.1016/j.biochi.2011.06.033
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 262–274
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human NAPRT kinetic assays and site-directed mutagenesis · source_derived_draft · unverified_draft
### b3-pre-naprt-phosphate Inorganic phosphate activated purified recombinant human NAPRT in the reported kinetic experiments. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phosphate supported this isolated precursor enzyme. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human NAPRT kinetic assays and site-directed mutagenesis limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention cross_nutrient: Phosphorus-containing inorganic phosphate alters a niacin precursor enzyme in vitro; no dietary phosphate deficiency was tested. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/naprt2011.abstract.txt", "locator": "Indexed primary abstract; identified exact passage", "start_char": 815, "end_char": 876, "file_sha256": "c9f4959ad65f0b0621179b3ccf00c460f7f648293bf910209ecc6e7785417deb", "text_sha256": "53af728f32d65092c92246c77801e92e521892adac900df62bf3f8206129f714"} [b3-pre-naprt2011] Characterization of human nicotinate phosphoribosyltransferase: Kinetic studies, structure prediction and functional analysis by site-directed mutagenesis. (2012). https://pubmed.ncbi.nlm.nih.gov/21742010/ DOI: 10.1016/j.biochi.2011.06.033
Complete structured claim and evidence
ATP stimulated or inhibited recombinant human NAPRT depending on low or high substrate saturation in the reported kinetic assays.
ATP → Human nicotinate phosphoribosyltransferase / NAPRT source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/naprt2011.abstract.txt", "locator": "Indexed primary abstract; identified exact passage", "start_char": 645, "end_char": 876, "file_sha256": "c9f4959ad65f0b0621179b3ccf00c460f7f648293bf910209ecc6e7785417deb", "text_sha256": "4c7ca81c7fa47c688d3b609b934e21bddf5bb0501b5bd8b54699ff7761280cb9"}
experimental_model
Purified recombinant human NAPRT kinetic assays and site-directed mutagenesis
exposure
Biochemical or structural assay; no dietary intervention
limitations
Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
ATP’s effect on this enzyme depended on the assay conditions.
primary_references
[b3-pre-naprt2011] Characterization of human nicotinate phosphoribosyltransferase: Kinetic studies, structure prediction and functional analysis by site-directed mutagenesis. (2012). https://pubmed.ncbi.nlm.nih.gov/21742010/ DOI: 10.1016/j.biochi.2011.06.033
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 276–287
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human NAPRT kinetic assays and site-directed mutagenesis · source_derived_draft · unverified_draft
### b3-pre-naprt-atp-context ATP stimulated or inhibited recombinant human NAPRT depending on low or high substrate saturation in the reported kinetic assays. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP’s effect on this enzyme depended on the assay conditions. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human NAPRT kinetic assays and site-directed mutagenesis limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/naprt2011.abstract.txt", "locator": "Indexed primary abstract; identified exact passage", "start_char": 645, "end_char": 876, "file_sha256": "c9f4959ad65f0b0621179b3ccf00c460f7f648293bf910209ecc6e7785417deb", "text_sha256": "4c7ca81c7fa47c688d3b609b934e21bddf5bb0501b5bd8b54699ff7761280cb9"} [b3-pre-naprt2011] Characterization of human nicotinate phosphoribosyltransferase: Kinetic studies, structure prediction and functional analysis by site-directed mutagenesis. (2012). https://pubmed.ncbi.nlm.nih.gov/21742010/ DOI: 10.1016/j.biochi.2011.06.033
Complete structured claim and evidence
Purified recombinant human NMNAT2 has adenylyltransferase activity toward NMN, supporting NAD+ formation.
Human nicotinamide mononucleotide adenylyltransferase 2 / NMNAT2 → NAD+ source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/nmnat2002.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 826, "file_sha256": "5064cc6a7b31875eeaea8def5544c3cce75a971f73aa74f332d89e06c3c54477", "text_sha256": "5064cc6a7b31875eeaea8def5544c3cce75a971f73aa74f332d89e06c3c54477"}
experimental_model
Cloned, expressed and purified recombinant human NMNAT2
exposure
Biochemical or structural assay; no dietary intervention
limitations
Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The same human isozyme processes either the amidated or deamidated mononucleotide.
primary_references
[b3-pre-nmnat2002] Identification of a novel human nicotinamide mononucleotide adenylyltransferase. (2002). https://pubmed.ncbi.nlm.nih.gov/12359228/ DOI: 10.1016/s0006-291x(02)02285-4
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 302–313
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloned, expressed and purified recombinant human NMNAT2 · source_derived_draft · unverified_draft
### b3-pre-nmnat2-nmn Purified recombinant human NMNAT2 has adenylyltransferase activity toward NMN, supporting NAD+ formation. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same human isozyme processes either the amidated or deamidated mononucleotide. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Cloned, expressed and purified recombinant human NMNAT2 limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nmnat2002.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 826, "file_sha256": "5064cc6a7b31875eeaea8def5544c3cce75a971f73aa74f332d89e06c3c54477", "text_sha256": "5064cc6a7b31875eeaea8def5544c3cce75a971f73aa74f332d89e06c3c54477"} [b3-pre-nmnat2002] Identification of a novel human nicotinamide mononucleotide adenylyltransferase. (2002). https://pubmed.ncbi.nlm.nih.gov/12359228/ DOI: 10.1016/s0006-291x(02)02285-4
Complete structured claim and evidence
Purified recombinant human NMNAT2 has adenylyltransferase activity toward nicotinic acid mononucleotide, supporting NaAD formation.
Human nicotinamide mononucleotide adenylyltransferase 2 / NMNAT2 → Nicotinic acid adenine dinucleotide source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/nmnat2002.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 826, "file_sha256": "5064cc6a7b31875eeaea8def5544c3cce75a971f73aa74f332d89e06c3c54477", "text_sha256": "5064cc6a7b31875eeaea8def5544c3cce75a971f73aa74f332d89e06c3c54477"}
experimental_model
Cloned, expressed and purified recombinant human NMNAT2
exposure
Biochemical or structural assay; no dietary intervention
limitations
Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The same human isozyme processes either the amidated or deamidated mononucleotide.
primary_references
[b3-pre-nmnat2002] Identification of a novel human nicotinamide mononucleotide adenylyltransferase. (2002). https://pubmed.ncbi.nlm.nih.gov/12359228/ DOI: 10.1016/s0006-291x(02)02285-4
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 315–326
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloned, expressed and purified recombinant human NMNAT2 · source_derived_draft · unverified_draft
### b3-pre-nmnat2-namn Purified recombinant human NMNAT2 has adenylyltransferase activity toward nicotinic acid mononucleotide, supporting NaAD formation. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same human isozyme processes either the amidated or deamidated mononucleotide. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Cloned, expressed and purified recombinant human NMNAT2 limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nmnat2002.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 826, "file_sha256": "5064cc6a7b31875eeaea8def5544c3cce75a971f73aa74f332d89e06c3c54477", "text_sha256": "5064cc6a7b31875eeaea8def5544c3cce75a971f73aa74f332d89e06c3c54477"} [b3-pre-nmnat2002] Identification of a novel human nicotinamide mononucleotide adenylyltransferase. (2002). https://pubmed.ncbi.nlm.nih.gov/12359228/ DOI: 10.1016/s0006-291x(02)02285-4
Complete structured claim and evidence
Purified human NADSYN1 catalyzed ATP-dependent NAD+ production from nicotinic acid adenine dinucleotide in glutamine-supported assays.
Human glutamine-dependent NAD synthetase / NADSYN1 → NAD+ source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Glutamine supplies nitrogen for the final amidation of the nicotinic-acid/de novo NAD pathway.
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/nadsyn2019.paragraphs.txt", "locator": "Normalized full-text paragraphs 8–8 (0-based)", "start_char": 7090, "end_char": 8684, "file_sha256": "36ad82ce734c8e0c44d01c7dc813b1641708738319b53a926e429155b1a602f4", "text_sha256": "90cb4d2ce3001f2ecf18f1d751db36047726b71a75be94b073474f6f518c96cd"}
experimental_model
Recombinant human NADSYN1 steady-state kinetic assays and crystallography; bacterial comparison kept separate
exposure
Biochemical or structural assay; no dietary intervention
limitations
Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The deamidated route finishes by making NAD+ through NADSYN1.
primary_references
[b3-pre-nadsyn2019] Different ways to transport ammonia in human and Mycobacterium tuberculosis NAD+ synthetases. (2020). https://pubmed.ncbi.nlm.nih.gov/31911602/ DOI: 10.1038/s41467-019-13845-4
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 328–340
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human NADSYN1 steady-state kinetic assays and crystallography; bacterial comparison kept separate · source_derived_draft · unverified_draft
### b3-pre-nadsyn-amidation Purified human NADSYN1 catalyzed ATP-dependent NAD+ production from nicotinic acid adenine dinucleotide in glutamine-supported assays. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The deamidated route finishes by making NAD+ through NADSYN1. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human NADSYN1 steady-state kinetic assays and crystallography; bacterial comparison kept separate limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention cross_nutrient: Glutamine supplies nitrogen for the final amidation of the nicotinic-acid/de novo NAD pathway. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nadsyn2019.paragraphs.txt", "locator": "Normalized full-text paragraphs 8–8 (0-based)", "start_char": 7090, "end_char": 8684, "file_sha256": "36ad82ce734c8e0c44d01c7dc813b1641708738319b53a926e429155b1a602f4", "text_sha256": "90cb4d2ce3001f2ecf18f1d751db36047726b71a75be94b073474f6f518c96cd"} [b3-pre-nadsyn2019] Different ways to transport ammonia in human and Mycobacterium tuberculosis NAD+ synthetases. (2020). https://pubmed.ncbi.nlm.nih.gov/31911602/ DOI: 10.1038/s41467-019-13845-4
Complete structured claim and evidence
Human NADSYN1 glutaminase activity was measured as glutamate production; NaAD plus ATP/Mg2+ increased that activity 31-fold over glutamine alone in the reported assay.
Human glutamine-dependent NAD synthetase / NADSYN1 → L-Glutamate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Glutamine nitrogen handling and magnesium-containing ATP chemistry couple in a niacin precursor enzyme.
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/nadsyn2019.paragraphs.txt", "locator": "Normalized full-text paragraphs 10–10 (0-based)", "start_char": 8754, "end_char": 10450, "file_sha256": "36ad82ce734c8e0c44d01c7dc813b1641708738319b53a926e429155b1a602f4", "text_sha256": "32dd95b3bef542cb15f227e9dd3de1ed68b6b9c8f6cda41d34daf7b6fe387ce7"}
experimental_model
Recombinant human NADSYN1 steady-state kinetic assays and crystallography; bacterial comparison kept separate
exposure
Biochemical or structural assay; no dietary intervention
limitations
Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The two enzyme activities communicate while NAD is assembled.
primary_references
[b3-pre-nadsyn2019] Different ways to transport ammonia in human and Mycobacterium tuberculosis NAD+ synthetases. (2020). https://pubmed.ncbi.nlm.nih.gov/31911602/ DOI: 10.1038/s41467-019-13845-4
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 342–354
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human NADSYN1 steady-state kinetic assays and crystallography; bacterial comparison kept separate · source_derived_draft · unverified_draft
### b3-pre-nadsyn-glutaminase Human NADSYN1 glutaminase activity was measured as glutamate production; NaAD plus ATP/Mg2+ increased that activity 31-fold over glutamine alone in the reported assay. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two enzyme activities communicate while NAD is assembled. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human NADSYN1 steady-state kinetic assays and crystallography; bacterial comparison kept separate limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention cross_nutrient: Glutamine nitrogen handling and magnesium-containing ATP chemistry couple in a niacin precursor enzyme. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nadsyn2019.paragraphs.txt", "locator": "Normalized full-text paragraphs 10–10 (0-based)", "start_char": 8754, "end_char": 10450, "file_sha256": "36ad82ce734c8e0c44d01c7dc813b1641708738319b53a926e429155b1a602f4", "text_sha256": "32dd95b3bef542cb15f227e9dd3de1ed68b6b9c8f6cda41d34daf7b6fe387ce7"} [b3-pre-nadsyn2019] Different ways to transport ammonia in human and Mycobacterium tuberculosis NAD+ synthetases. (2020). https://pubmed.ncbi.nlm.nih.gov/31911602/ DOI: 10.1038/s41467-019-13845-4
Complete structured claim and evidence
Human QPRT converts quinolinate and PRPP toward nicotinic acid mononucleotide; the human enzyme structures resolve reactant quinolinate and product NaMN complexes.
Human quinolinate phosphoribosyltransferase / QPRT → Nicotinic acid mononucleotide source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/qprt2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 13–15 (0-based)", "start_char": 10597, "end_char": 15612, "file_sha256": "85fcc4a79a17f4f3846301f67698a444c3c9930829e167d86a96adbb72d830e6", "text_sha256": "8da78d25a53af6507018eece4ce553705dc505d0b169f678affad49ee21b10f6"}
experimental_model
Purified recombinant human QPRT crystallography, calorimetry and oligomer studies
exposure
Biochemical or structural assay; no dietary intervention
limitations
Structural and biochemical enzyme study; does not establish how much dietary tryptophan becomes NAD in a person.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Quinolinate enters the same deamidated mononucleotide route used by nicotinic acid.
primary_references
[b3-pre-qprt2016] Structural Insights into the Quaternary Catalytic Mechanism of Hexameric Human Quinolinate Phosphoribosyltransferase, a Key Enzyme in de novo NAD Biosynthesis. (2016). https://pubmed.ncbi.nlm.nih.gov/26805589/ DOI: 10.1038/srep19681
supporting_evidence_spans
[{"source_cache": "artifacts/niacin-precursors-sources/qprt2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 4–4 (0-based)", "start_char": 1453, "end_char": 3871, "file_sha256": "85fcc4a79a17f4f3846301f67698a444c3c9930829e167d86a96adbb72d830e6", "text_sha256": "be14ed97ccf53b635f2cb35969188ce42c84dd739db897a24cbf3e65d8a3e3d1"}]
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 537–549
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human QPRT crystallography, calorimetry and oligomer studies · source_derived_draft · unverified_draft
### b3-pre-qprt-namn Human QPRT converts quinolinate and PRPP toward nicotinic acid mononucleotide; the human enzyme structures resolve reactant quinolinate and product NaMN complexes. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Quinolinate enters the same deamidated mononucleotide route used by nicotinic acid. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human QPRT crystallography, calorimetry and oligomer studies limitations: Structural and biochemical enzyme study; does not establish how much dietary tryptophan becomes NAD in a person. exposure: Biochemical or structural assay; no dietary intervention evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/qprt2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 13–15 (0-based)", "start_char": 10597, "end_char": 15612, "file_sha256": "85fcc4a79a17f4f3846301f67698a444c3c9930829e167d86a96adbb72d830e6", "text_sha256": "8da78d25a53af6507018eece4ce553705dc505d0b169f678affad49ee21b10f6"} supporting_evidence_spans: [{"source_cache": "artifacts/niacin-precursors-sources/qprt2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 4–4 (0-based)", "start_char": 1453, "end_char": 3871, "file_sha256": "85fcc4a79a17f4f3846301f67698a444c3c9930829e167d86a96adbb72d830e6", "text_sha256": "be14ed97ccf53b635f2cb35969188ce42c84dd739db897a24cbf3e65d8a3e3d1"}] [b3-pre-qprt2016] Structural Insights into the Quaternary Catalytic Mechanism of Hexameric Human Quinolinate Phosphoribosyltransferase, a Key Enzyme in de novo NAD Biosynthesis. (2016). https://pubmed.ncbi.nlm.nih.gov/26805589/ DOI: 10.1038/srep19681
Complete structured claim and evidence
Primary hepatocytes from Nmrk1-knockout mice failed to increase NAD+ after NR treatment, whereas wild-type hepatocytes responded.
Mouse Nmrk1 knockout genotype → NAD+ source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 14–14 (0-based)", "start_char": 14813, "end_char": 16096, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "fcfc45b2ce45c05afffe5608ea3be48fe50bd17083c12f5b0993f3bc183da63f"}
experimental_model
Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments
exposure
0.5 mM NR for 6 h (Fig. 5e)
limitations
Isolated hepatocytes. Whole-animal liver retained substantial response after injected NR/NMN; the claim is not universal direct-uptake exclusion.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Mus musculus
plain_language
The precursor response required NRK1 in these isolated liver cells.
primary_references
[b3-pre-nmrk2016] NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27725675/ DOI: 10.1038/ncomms13103
supporting_evidence_spans
[{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 52–52 (0-based)", "start_char": 47696, "end_char": 48288, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "541856eddb8e5c1162040cb1e010a6d556de92ee36f223d0da751b4c53b06104"}]
tissue_or_cell_type
Primary hepatocytes from male mice aged 10–15 weeks
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 423–435
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments · source_derived_draft · unverified_draft
### b3-pre-nrk1ko-nr Primary hepatocytes from Nmrk1-knockout mice failed to increase NAD+ after NR treatment, whereas wild-type hepatocytes responded. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The precursor response required NRK1 in these isolated liver cells. organism: Mus musculus tissue_or_cell_type: Primary hepatocytes from male mice aged 10–15 weeks experimental_model: Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments limitations: Isolated hepatocytes. Whole-animal liver retained substantial response after injected NR/NMN; the claim is not universal direct-uptake exclusion. exposure: 0.5 mM NR for 6 h (Fig. 5e) evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 14–14 (0-based)", "start_char": 14813, "end_char": 16096, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "fcfc45b2ce45c05afffe5608ea3be48fe50bd17083c12f5b0993f3bc183da63f"} supporting_evidence_spans: [{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 52–52 (0-based)", "start_char": 47696, "end_char": 48288, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "541856eddb8e5c1162040cb1e010a6d556de92ee36f223d0da751b4c53b06104"}] [b3-pre-nmrk2016] NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27725675/ DOI: 10.1038/ncomms13103
Complete structured claim and evidence
Primary hepatocytes from Nmrk1-knockout mice failed to increase NAD+ after NMN treatment, whereas wild-type hepatocytes responded.
Mouse Nmrk1 knockout genotype → NAD+ source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 14–14 (0-based)", "start_char": 14813, "end_char": 16096, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "fcfc45b2ce45c05afffe5608ea3be48fe50bd17083c12f5b0993f3bc183da63f"}
experimental_model
Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments
exposure
0.5 mM NMN for 6 h (Fig. 5e)
limitations
Isolated hepatocytes. Whole-animal liver retained substantial response after injected NR/NMN; the claim is not universal direct-uptake exclusion.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Mus musculus
plain_language
The precursor response required NRK1 in these isolated liver cells.
primary_references
[b3-pre-nmrk2016] NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27725675/ DOI: 10.1038/ncomms13103
supporting_evidence_spans
[{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 52–52 (0-based)", "start_char": 47696, "end_char": 48288, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "541856eddb8e5c1162040cb1e010a6d556de92ee36f223d0da751b4c53b06104"}]
tissue_or_cell_type
Primary hepatocytes from male mice aged 10–15 weeks
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 437–449
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments · source_derived_draft · unverified_draft
### b3-pre-nrk1ko-nmn Primary hepatocytes from Nmrk1-knockout mice failed to increase NAD+ after NMN treatment, whereas wild-type hepatocytes responded. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The precursor response required NRK1 in these isolated liver cells. organism: Mus musculus tissue_or_cell_type: Primary hepatocytes from male mice aged 10–15 weeks experimental_model: Murine NRK gain/loss of function in fibroblasts and primary hepatocytes; separate human HepG2 stable-isotope experiments limitations: Isolated hepatocytes. Whole-animal liver retained substantial response after injected NR/NMN; the claim is not universal direct-uptake exclusion. exposure: 0.5 mM NMN for 6 h (Fig. 5e) evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 14–14 (0-based)", "start_char": 14813, "end_char": 16096, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "fcfc45b2ce45c05afffe5608ea3be48fe50bd17083c12f5b0993f3bc183da63f"} supporting_evidence_spans: [{"source_cache": "artifacts/niacin-precursors-sources/nmrk2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 52–52 (0-based)", "start_char": 47696, "end_char": 48288, "file_sha256": "fcbd5465aff51c9870d65fc9812edbad2cdf2af8bb16b6afb3170d7f0503178a", "text_sha256": "541856eddb8e5c1162040cb1e010a6d556de92ee36f223d0da751b4c53b06104"}] [b3-pre-nmrk2016] NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27725675/ DOI: 10.1038/ncomms13103
Complete structured claim and evidence
SLC25A51 loss reduced mitochondrial NAD+ availability in the tested human cell models.
SLC25A51 depletion or knockout → Mitochondrial NAD+ content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/slc25a51-2020.author.txt", "locator": "Publisher PDF, results; page/figure identified by adjacent text", "start_char": 6119, "end_char": 6538, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "024f4688a65e3279f2865ef892f19ed4d5357469c71a5e2e6fb27fe1a2dd4043"}
experimental_model
Multiple shRNA/siRNA perturbations; mitochondrial assays and biosensors
exposure
SLC25A51 RNA interference
limitations
Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Cells can lose mitochondrial NAD even when the total-cell pool is maintained.
primary_references
[slc25a51-2020] SLC25A51 is a mammalian mitochondrial NAD+ transporter. (2020). https://pubmed.ncbi.nlm.nih.gov/32906142/ DOI: 10.1038/s41586-020-2741-7
tissue_or_cell_type
Human cultured cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1042–1053
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multiple shRNA/siRNA perturbations; mitochondrial assays and biosensors · source_derived_draft · unverified_draft
### b3-redox-slc25a51-mito-pool SLC25A51 loss reduced mitochondrial NAD+ availability in the tested human cell models. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells can lose mitochondrial NAD even when the total-cell pool is maintained. organism: Homo sapiens tissue_or_cell_type: Human cultured cells experimental_model: Multiple shRNA/siRNA perturbations; mitochondrial assays and biosensors limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: SLC25A51 RNA interference evidence_span: {"source_cache": "artifacts/niacin-redox-sources/slc25a51-2020.author.txt", "locator": "Publisher PDF, results; page/figure identified by adjacent text", "start_char": 6119, "end_char": 6538, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "024f4688a65e3279f2865ef892f19ed4d5357469c71a5e2e6fb27fe1a2dd4043"} [slc25a51-2020] SLC25A51 is a mammalian mitochondrial NAD+ transporter. (2020). https://pubmed.ncbi.nlm.nih.gov/32906142/ DOI: 10.1038/s41586-020-2741-7
Complete structured claim and evidence
SLC25A51 loss did not reduce whole-cell NAD+ content in the comparisons that showed mitochondrial depletion.
SLC25A51 depletion or knockout → Whole-cell NAD+ content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/slc25a51-2020.author.txt", "locator": "Publisher PDF, results; page/figure identified by adjacent text", "start_char": 6119, "end_char": 6538, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "024f4688a65e3279f2865ef892f19ed4d5357469c71a5e2e6fb27fe1a2dd4043"}
experimental_model
RNA interference and whole-cell NAD measurements
exposure
SLC25A51 depletion
limitations
Scoped null result; total NAD is not a universal proxy for mitochondrial NAD availability.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
A total-cell measurement did not reveal the compartment-specific deficit.
primary_references
[slc25a51-2020] SLC25A51 is a mammalian mitochondrial NAD+ transporter. (2020). https://pubmed.ncbi.nlm.nih.gov/32906142/ DOI: 10.1038/s41586-020-2741-7
tissue_or_cell_type
Human cell lines
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1055–1066
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RNA interference and whole-cell NAD measurements · source_derived_draft · unverified_draft
### b3-redox-slc25a51-whole-cell-null SLC25A51 loss did not reduce whole-cell NAD+ content in the comparisons that showed mitochondrial depletion. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A total-cell measurement did not reveal the compartment-specific deficit. organism: Homo sapiens tissue_or_cell_type: Human cell lines experimental_model: RNA interference and whole-cell NAD measurements limitations: Scoped null result; total NAD is not a universal proxy for mitochondrial NAD availability. exposure: SLC25A51 depletion evidence_span: {"source_cache": "artifacts/niacin-redox-sources/slc25a51-2020.author.txt", "locator": "Publisher PDF, results; page/figure identified by adjacent text", "start_char": 6119, "end_char": 6538, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "024f4688a65e3279f2865ef892f19ed4d5357469c71a5e2e6fb27fe1a2dd4043"} [slc25a51-2020] SLC25A51 is a mammalian mitochondrial NAD+ transporter. (2020). https://pubmed.ncbi.nlm.nih.gov/32906142/ DOI: 10.1038/s41586-020-2741-7
Complete structured claim and evidence
Re-expression of SLC25A51 restored exogenous NAD+ uptake into mitochondria isolated from SLC25A51-deficient cells.
SLC25A51 → Mitochondrial NAD+ uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/slc25a51-2020.author.txt", "locator": "Publisher PDF, results; page/figure identified by adjacent text", "start_char": 18765, "end_char": 19491, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "151d453cb71149ec656b6e82375a1e679d977643e107133d197cac4a5df0f7b9"}
experimental_model
HEK293T knockdown and HAP1 knockout mitochondria with genetic rescue
exposure
1 mM exogenous NAD+; 40-min uptake incubation
limitations
Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The transporter restored mitochondrial entry of intact NAD+.
primary_references
[slc25a51-2020] SLC25A51 is a mammalian mitochondrial NAD+ transporter. (2020). https://pubmed.ncbi.nlm.nih.gov/32906142/ DOI: 10.1038/s41586-020-2741-7
tissue_or_cell_type
Isolated mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1029–1040
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HEK293T knockdown and HAP1 knockout mitochondria with genetic rescue · source_derived_draft · unverified_draft
### b3-redox-slc25a51-import Re-expression of SLC25A51 restored exogenous NAD+ uptake into mitochondria isolated from SLC25A51-deficient cells. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The transporter restored mitochondrial entry of intact NAD+. organism: Homo sapiens tissue_or_cell_type: Isolated mitochondria experimental_model: HEK293T knockdown and HAP1 knockout mitochondria with genetic rescue limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: 1 mM exogenous NAD+; 40-min uptake incubation evidence_span: {"source_cache": "artifacts/niacin-redox-sources/slc25a51-2020.author.txt", "locator": "Publisher PDF, results; page/figure identified by adjacent text", "start_char": 18765, "end_char": 19491, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "151d453cb71149ec656b6e82375a1e679d977643e107133d197cac4a5df0f7b9"} [slc25a51-2020] SLC25A51 is a mammalian mitochondrial NAD+ transporter. (2020). https://pubmed.ncbi.nlm.nih.gov/32906142/ DOI: 10.1038/s41586-020-2741-7
Complete structured claim and evidence
Restoration of mitochondrial NAD+ by nicotinamide riboside in the intact-cell biosensor experiment depended on SLC25A51.
SLC25A51 → Mitochondrial NAD+ content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
[{"source_cache": "artifacts/niacin-redox-sources/slc25a51-2020.author.txt", "locator": "Publisher PDF, results; page/figure identified by adjacent text", "start_char": 19922, "end_char": 20160, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "78e9cfd3c25b8d33b54ac67bebc01314eed3925b3b6a4bdea527d48191da0977"}, {"source_cache": "artifacts/niacin-redox-sources/slc25a51-2020.author.txt", "locator": "Publisher PDF, results; page/figure identified by adjacent text", "start_char": 24477, "end_char": 24725, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "7125713c87024da0a0f8c1d4442115144c9ff20543fbd39cfc4cfc46de135cad"}]
experimental_model
HeLa siRNA and mitochondrial NAD biosensor
exposure
100 μM NR for 16 h after siRNA transfection three days earlier
limitations
Cultured-cell precursor response; no direct clinical inference or generic claim that every NAD-raising intervention fails.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Precursor provision still required functional mitochondrial import in these cells.
primary_references
[slc25a51-2020] SLC25A51 is a mammalian mitochondrial NAD+ transporter. (2020). https://pubmed.ncbi.nlm.nih.gov/32906142/ DOI: 10.1038/s41586-020-2741-7
tissue_or_cell_type
HeLa cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1094–1105
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HeLa siRNA and mitochondrial NAD biosensor · source_derived_draft · unverified_draft
### b3-redox-slc25a51-nr-dependence Restoration of mitochondrial NAD+ by nicotinamide riboside in the intact-cell biosensor experiment depended on SLC25A51. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Precursor provision still required functional mitochondrial import in these cells. organism: Homo sapiens tissue_or_cell_type: HeLa cells experimental_model: HeLa siRNA and mitochondrial NAD biosensor limitations: Cultured-cell precursor response; no direct clinical inference or generic claim that every NAD-raising intervention fails. exposure: 100 μM NR for 16 h after siRNA transfection three days earlier evidence_span: [{"source_cache": "artifacts/niacin-redox-sources/slc25a51-2020.author.txt", "locator": "Publisher PDF, results; page/figure identified by adjacent text", "start_char": 19922, "end_char": 20160, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "78e9cfd3c25b8d33b54ac67bebc01314eed3925b3b6a4bdea527d48191da0977"}, {"source_cache": "artifacts/niacin-redox-sources/slc25a51-2020.author.txt", "locator": "Publisher PDF, results; page/figure identified by adjacent text", "start_char": 24477, "end_char": 24725, "file_sha256": "8348dbfda6d16d576bb64301f0c75f1488e90e33c4a72213b69756bed21d047d", "text_sha256": "7125713c87024da0a0f8c1d4442115144c9ff20543fbd39cfc4cfc46de135cad"}] [slc25a51-2020] SLC25A51 is a mammalian mitochondrial NAD+ transporter. (2020). https://pubmed.ncbi.nlm.nih.gov/32906142/ DOI: 10.1038/s41586-020-2741-7
Complete structured claim and evidence
Purified full-length human NADK catalyzed NADP+ production from NAD+ in a coupled assay supplied with 5 mM MgATP.
NADK → NADP+ source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Mg-ATP supplies the phosphate donor for generating niacin-derived NADP+. NADP+ production is distinct from its later reduction to NADPH.
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/nadk-human-2025.fulltext.txt", "locator": "Results", "start_char": 53525, "end_char": 54577, "file_sha256": "72c7b9625e1bf4137d6833adac6ae49fc108f2cd75bb4945c5b04d72a0355f9b", "text_sha256": "db49fc47ad605562e1c1cf93e1b39596505906831ae509e7ec0031485f84ba4f"}
experimental_model
Full-length recombinant human NADK; G6PD-coupled assay
exposure
5 mM MgATP; 0.1–2 mM NAD+; 1 mM additional MgCl2; 30°C
limitations
Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The cytosolic kinase makes the phosphorylated cofactor using magnesium-associated ATP.
primary_references
[nadk-human-2025] Cryo-EM structure and regulation of human NAD kinase. (2025). https://pubmed.ncbi.nlm.nih.gov/39854463/ DOI: 10.1126/sciadv.ads2664
tissue_or_cell_type
Purified enzyme
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 831–843
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Full-length recombinant human NADK; G6PD-coupled assay · source_derived_draft · unverified_draft
### b3-redox-nadk-mgatp Purified full-length human NADK catalyzed NADP+ production from NAD+ in a coupled assay supplied with 5 mM MgATP. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cytosolic kinase makes the phosphorylated cofactor using magnesium-associated ATP. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Full-length recombinant human NADK; G6PD-coupled assay limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: 5 mM MgATP; 0.1–2 mM NAD+; 1 mM additional MgCl2; 30°C cross_nutrient: Mg-ATP supplies the phosphate donor for generating niacin-derived NADP+. NADP+ production is distinct from its later reduction to NADPH. evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk-human-2025.fulltext.txt", "locator": "Results", "start_char": 53525, "end_char": 54577, "file_sha256": "72c7b9625e1bf4137d6833adac6ae49fc108f2cd75bb4945c5b04d72a0355f9b", "text_sha256": "db49fc47ad605562e1c1cf93e1b39596505906831ae509e7ec0031485f84ba4f"} [nadk-human-2025] Cryo-EM structure and regulation of human NAD kinase. (2025). https://pubmed.ncbi.nlm.nih.gov/39854463/ DOI: 10.1126/sciadv.ads2664
Complete structured claim and evidence
Full-length human NADK2 localized to mitochondria in HEK293A cells; deletion of its first 62 residues disrupted that localization.
NADK2 → Mitochondria source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 12522, "end_char": 13722, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "bdd61af93db3bf8e573fc599daf7a38da7f5b844d9b5da00d86e955657611875"}
experimental_model
FLAG-tagged proteins and endogenous-protein fractionation
exposure
Full-length versus Δ62 construct
limitations
Evidence resolves mitochondrial localization, not precise submitochondrial position.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The N-terminal targeting region directs this kinase into mitochondria.
primary_references
[nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
tissue_or_cell_type
HEK293A cells
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 912–923
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · FLAG-tagged proteins and endogenous-protein fractionation · source_derived_draft · unverified_draft
### b3-redox-nadk2-localization Full-length human NADK2 localized to mitochondria in HEK293A cells; deletion of its first 62 residues disrupted that localization. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The N-terminal targeting region directs this kinase into mitochondria. organism: Homo sapiens tissue_or_cell_type: HEK293A cells experimental_model: FLAG-tagged proteins and endogenous-protein fractionation limitations: Evidence resolves mitochondrial localization, not precise submitochondrial position. exposure: Full-length versus Δ62 construct evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 12522, "end_char": 13722, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "bdd61af93db3bf8e573fc599daf7a38da7f5b844d9b5da00d86e955657611875"} [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
Complete structured claim and evidence
NADK2 knockdown reduced measured mitochondrial-fraction NAD kinase activity to 47% of control in HEK293A cells.
NADK2 → Mitochondrial NAD kinase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 16830, "end_char": 18219, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "5de49f80d76c73b6a308096c07b330e8d3d53ee28c6a06f4b2a331e4798b45d7"}
experimental_model
siRNA knockdown
exposure
Three days after siRNA transfection
limitations
Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Reducing the kinase reduced the mitochondrial capacity to make NADP+.
primary_references
[nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
tissue_or_cell_type
HEK293A mitochondrial fraction
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 925–936
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · siRNA knockdown · source_derived_draft · unverified_draft
### b3-redox-nadk2-knockdown-activity NADK2 knockdown reduced measured mitochondrial-fraction NAD kinase activity to 47% of control in HEK293A cells. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing the kinase reduced the mitochondrial capacity to make NADP+. organism: Homo sapiens tissue_or_cell_type: HEK293A mitochondrial fraction experimental_model: siRNA knockdown limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: Three days after siRNA transfection evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 16830, "end_char": 18219, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "5de49f80d76c73b6a308096c07b330e8d3d53ee28c6a06f4b2a331e4798b45d7"} [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
Complete structured claim and evidence
Three days after NADK2 knockdown, HEK293A intracellular ROS-probe signals increased with and without the tested menadione challenge.
NADK2 → Cellular ROS assay signal source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 16830, "end_char": 18219, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "5de49f80d76c73b6a308096c07b330e8d3d53ee28c6a06f4b2a331e4798b45d7"}
experimental_model
siRNA knockdown; CM-H2DCFDA readout
exposure
Three-day knockdown; vehicle or 100 μM menadione for 30 min in ROS assay
limitations
CM-H2DCFDA is an intracellular probe; do not relabel this result as a direct measurement of mitochondrial ROS or assume dietary niacin deficiency.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Loss of the kinase increased a cellular oxidant readout in this experiment.
primary_references
[nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
tissue_or_cell_type
HEK293A cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 938–949
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · siRNA knockdown; CM-H2DCFDA readout · source_derived_draft · unverified_draft
### b3-redox-nadk2-knockdown-ros Three days after NADK2 knockdown, HEK293A intracellular ROS-probe signals increased with and without the tested menadione challenge. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of the kinase increased a cellular oxidant readout in this experiment. organism: Homo sapiens tissue_or_cell_type: HEK293A cells experimental_model: siRNA knockdown; CM-H2DCFDA readout limitations: CM-H2DCFDA is an intracellular probe; do not relabel this result as a direct measurement of mitochondrial ROS or assume dietary niacin deficiency. exposure: Three-day knockdown; vehicle or 100 μM menadione for 30 min in ROS assay evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 16830, "end_char": 18219, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "5de49f80d76c73b6a308096c07b330e8d3d53ee28c6a06f4b2a331e4798b45d7"} [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
Complete structured claim and evidence
Transfection with functional NADK2 rescued deficient DECR activity in the patient-cell experiments.
NADK2 → Dienoyl-CoA reductase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/nadk2-patient-2014.abstract.txt", "locator": "Indexed abstract, rescue experiment", "start_char": 706, "end_char": 1462, "file_sha256": "0e8ce719f0454f41ce98a5c35f75c88a21f5219f0d9b574cf8a793697f39db5a", "text_sha256": "3e8d0b720e24732ab8f9603138f761f1dc2974876c1f81919cf5ecdae2f71eeb"}
experimental_model
Functional NADK2 transfection of patient fibroblasts
exposure
Genetic complementation
limitations
Cellular gene rescue; neither dietary niacin nor NADPH dosing was shown to reproduce it.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Replacing the defective kinase restored the enzyme readout in cells.
primary_references
[nadk2-patient-2014] Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia. (2014). https://pubmed.ncbi.nlm.nih.gov/24847004/ DOI: 10.1093/hmg/ddu218
tissue_or_cell_type
Fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 990–1001
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Functional NADK2 transfection of patient fibroblasts · source_derived_draft · unverified_draft
### b3-redox-nadk2-patient-decr-rescue Transfection with functional NADK2 rescued deficient DECR activity in the patient-cell experiments. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing the defective kinase restored the enzyme readout in cells. organism: Homo sapiens tissue_or_cell_type: Fibroblasts experimental_model: Functional NADK2 transfection of patient fibroblasts limitations: Cellular gene rescue; neither dietary niacin nor NADPH dosing was shown to reproduce it. exposure: Genetic complementation evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-patient-2014.abstract.txt", "locator": "Indexed abstract, rescue experiment", "start_char": 706, "end_char": 1462, "file_sha256": "0e8ce719f0454f41ce98a5c35f75c88a21f5219f0d9b574cf8a793697f39db5a", "text_sha256": "3e8d0b720e24732ab8f9603138f761f1dc2974876c1f81919cf5ecdae2f71eeb"} [nadk2-patient-2014] Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia. (2014). https://pubmed.ncbi.nlm.nih.gov/24847004/ DOI: 10.1093/hmg/ddu218
Complete structured claim and evidence
Structural analysis of mammalian NNT supported coupling of NADH-to-NADP+ hydride transfer to proton translocation across the mitochondrial membrane.
Ovine NNT → NADPH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/nnt-structure-2019.abstract.txt", "locator": "Indexed abstract, reaction and structural mechanism", "start_char": 199, "end_char": 1759, "file_sha256": "edb35c2cdf2f57d604cb86da48665e5742d398f43c50f3e1622d161564c78a83", "text_sha256": "aa5063e57c35097c2fa2557ed9a7d61c3a411d90d0ded9b947525012520a5712"}
experimental_model
Cryo-EM of intact ovine NNT in different nucleotide states
exposure
Nucleotide-bound conformational states
limitations
Structural mechanism supported in ovine protein; forward flux is context dependent and not equivalent to adding phosphate to NAD. No human intake inference.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Ovis aries
plain_language
NNT links the NADH and NADPH redox systems through membrane-coupled chemistry.
primary_references
[nnt-structure-2019] Structure and mechanism of mitochondrial proton-translocating transhydrogenase. (2019). https://pubmed.ncbi.nlm.nih.gov/31462775/ DOI: 10.1038/s41586-019-1519-2
tissue_or_cell_type
Purified mitochondrial protein
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1003–1014
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of intact ovine NNT in different nucleotide states · source_derived_draft · unverified_draft
### b3-redox-nnt-coupling Structural analysis of mammalian NNT supported coupling of NADH-to-NADP+ hydride transfer to proton translocation across the mitochondrial membrane. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NNT links the NADH and NADPH redox systems through membrane-coupled chemistry. organism: Ovis aries tissue_or_cell_type: Purified mitochondrial protein experimental_model: Cryo-EM of intact ovine NNT in different nucleotide states limitations: Structural mechanism supported in ovine protein; forward flux is context dependent and not equivalent to adding phosphate to NAD. No human intake inference. exposure: Nucleotide-bound conformational states evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nnt-structure-2019.abstract.txt", "locator": "Indexed abstract, reaction and structural mechanism", "start_char": 199, "end_char": 1759, "file_sha256": "edb35c2cdf2f57d604cb86da48665e5742d398f43c50f3e1622d161564c78a83", "text_sha256": "aa5063e57c35097c2fa2557ed9a7d61c3a411d90d0ded9b947525012520a5712"} [nnt-structure-2019] Structure and mechanism of mitochondrial proton-translocating transhydrogenase. (2019). https://pubmed.ncbi.nlm.nih.gov/31462775/ DOI: 10.1038/s41586-019-1519-2
Complete structured claim and evidence
In the cardiac pathological-workload study, reverse-mode Nnt consumed NADPH while supporting NADH and ATP production.
Mouse Nnt → NADPH source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/nnt-reverse-2015.abstract.txt", "locator": "Indexed abstract, pathological workload results", "start_char": 373, "end_char": 1028, "file_sha256": "88e6510d357946cd087e5af7ca3c9fdfd2ac22f2fb1851dd1164f176c5e39ce4", "text_sha256": "a8e2d67ccb1f5f041786aecfb33760602a804017dccfe41c54b34213ea0c6223"}
experimental_model
Mouse cardiac pressure-overload / pathological-demand experiments
exposure
Pathological cardiac metabolic demand
limitations
Context-dependent reversal, not genetic kinase failure or dietary niacin deficiency. Abstract-only extraction; do not generalize to all hearts or propose NNT inhibition clinically.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Mus musculus
plain_language
Under this high-workload condition Nnt used up NADPH instead of supplying it.
primary_references
[nnt-reverse-2015] Reversal of Mitochondrial Transhydrogenase Causes Oxidative Stress in Heart Failure. (2015). https://pubmed.ncbi.nlm.nih.gov/26256392/ DOI: 10.1016/j.cmet.2015.07.008
tissue_or_cell_type
Heart
trigger_kind
machinery_impairment Imported condition classification; unverified.
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1016–1027
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse cardiac pressure-overload / pathological-demand experiments · source_derived_draft · unverified_draft
### b3-redox-nnt-reversal In the cardiac pathological-workload study, reverse-mode Nnt consumed NADPH while supporting NADH and ATP production. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Under this high-workload condition Nnt used up NADPH instead of supplying it. organism: Mus musculus tissue_or_cell_type: Heart experimental_model: Mouse cardiac pressure-overload / pathological-demand experiments limitations: Context-dependent reversal, not genetic kinase failure or dietary niacin deficiency. Abstract-only extraction; do not generalize to all hearts or propose NNT inhibition clinically. exposure: Pathological cardiac metabolic demand evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nnt-reverse-2015.abstract.txt", "locator": "Indexed abstract, pathological workload results", "start_char": 373, "end_char": 1028, "file_sha256": "88e6510d357946cd087e5af7ca3c9fdfd2ac22f2fb1851dd1164f176c5e39ce4", "text_sha256": "a8e2d67ccb1f5f041786aecfb33760602a804017dccfe41c54b34213ea0c6223"} [nnt-reverse-2015] Reversal of Mitochondrial Transhydrogenase Causes Oxidative Stress in Heart Failure. (2015). https://pubmed.ncbi.nlm.nih.gov/26256392/ DOI: 10.1016/j.cmet.2015.07.008
Complete structured claim and evidence
Human CD38 hydrolyzes NAD+ to free ADP-ribose and nicotinamide.
Human CD38 → NAD+ source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/niacin-consumption-sources/cd381998.abstract.txt", "locator": "Indexed abstract", "start_char": 0, "end_char": 1755, "file_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad", "text_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad"}
experimental_model
Biochemical characterization of human CD38
exposure
NAD+ as substrate
limitations
Primary human enzyme study; source abstract used. Product proportions are assay-specific and do not establish tissue flux or supplementation outcomes.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human
plain_language
CD38 can break NAD into ADP-ribose and nicotinamide.
primary_references
[b3-cons-cd381998] Human CD38 is an authentic NAD(P)+ glycohydrolase. (1998). https://pubmed.ncbi.nlm.nih.gov/9494110/ DOI: 10.1042/bj3301383
tissue_or_cell_type
Cell-free enzyme preparation
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 565–577
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical characterization of human CD38 · source_derived_draft · unverified_draft
### b3-cons-cd38-hydrolysis Human CD38 hydrolyzes NAD+ to free ADP-ribose and nicotinamide. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: CD38 can break NAD into ADP-ribose and nicotinamide. organism: Human tissue_or_cell_type: Cell-free enzyme preparation experimental_model: Biochemical characterization of human CD38 limitations: Primary human enzyme study; source abstract used. Product proportions are assay-specific and do not establish tissue flux or supplementation outcomes. exposure: NAD+ as substrate cross_nutrient: false evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/cd381998.abstract.txt", "locator": "Indexed abstract", "start_char": 0, "end_char": 1755, "file_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad", "text_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad"} [b3-cons-cd381998] Human CD38 is an authentic NAD(P)+ glycohydrolase. (1998). https://pubmed.ncbi.nlm.nih.gov/9494110/ DOI: 10.1042/bj3301383
Complete structured claim and evidence
Human CD38 produces cyclic ADP-ribose as a low-efficiency branch of NAD+ cleavage.
Human CD38 → Cyclic ADP-ribose source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/niacin-consumption-sources/cd381998.abstract.txt", "locator": "Indexed abstract", "start_char": 0, "end_char": 1755, "file_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad", "text_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad"}
experimental_model
Biochemical characterization of human CD38
exposure
NAD+ as substrate
limitations
Primary human enzyme study; source abstract used. Product proportions are assay-specific and do not establish tissue flux or supplementation outcomes.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human
plain_language
Some CD38 cleavage produces the cyclic calcium messenger.
primary_references
[b3-cons-cd381998] Human CD38 is an authentic NAD(P)+ glycohydrolase. (1998). https://pubmed.ncbi.nlm.nih.gov/9494110/ DOI: 10.1042/bj3301383
tissue_or_cell_type
Cell-free enzyme preparation
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 579–591
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical characterization of human CD38 · source_derived_draft · unverified_draft
### b3-cons-cd38-cyclization Human CD38 produces cyclic ADP-ribose as a low-efficiency branch of NAD+ cleavage. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some CD38 cleavage produces the cyclic calcium messenger. organism: Human tissue_or_cell_type: Cell-free enzyme preparation experimental_model: Biochemical characterization of human CD38 limitations: Primary human enzyme study; source abstract used. Product proportions are assay-specific and do not establish tissue flux or supplementation outcomes. exposure: NAD+ as substrate cross_nutrient: false evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/cd381998.abstract.txt", "locator": "Indexed abstract", "start_char": 0, "end_char": 1755, "file_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad", "text_sha256": "39f90bb382ddfee34e808fc93c5a1afafc1d9638a9dc73f2770e815827b4f2ad"} [b3-cons-cd381998] Human CD38 is an authentic NAD(P)+ glycohydrolase. (1998). https://pubmed.ncbi.nlm.nih.gov/9494110/ DOI: 10.1042/bj3301383
Complete structured claim and evidence
Purified human SARM1 TIR domain cleaved NAD+, producing ADP-ribose and nicotinamide as major products.
Human SARM1 TIR-domain construct → NAD+ source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/niacin-consumption-sources/sarm2017.txt", "locator": "Full text, normalized paragraph 24", "start_char": 15550, "end_char": 16946, "file_sha256": "fc30de231911f5c30425173d684495e62c725ba27c78d44592e6bc68433ef545", "text_sha256": "9a9b91a772186c34d8b6305a04bbcf6d3acc40b0448e6f478811527c5174981e"}
experimental_model
Purified human SARM1 TIR domain; HPLC and LC-MS/MS
exposure
NAD+ incubation
limitations
Purified engineered TIR fragment rather than basal activity of intact full-length SARM1; no dietary dose inference.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human
plain_language
SARM1 contains a catalytic domain that breaks NAD.
primary_references
[b3-cons-sarm2017] The SARM1 Toll/Interleukin-1 Receptor Domain Possesses Intrinsic NAD+ Cleavage Activity that Promotes Pathological Axonal Degeneration. (2017). https://pubmed.ncbi.nlm.nih.gov/28334607/ DOI: 10.1016/j.neuron.2017.02.022
tissue_or_cell_type
Cell-free preparation
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 677–689
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SARM1 TIR domain; HPLC and LC-MS/MS · source_derived_draft · unverified_draft
### b3-cons-sarm-adpr-nam Purified human SARM1 TIR domain cleaved NAD+, producing ADP-ribose and nicotinamide as major products. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: SARM1 contains a catalytic domain that breaks NAD. organism: Human tissue_or_cell_type: Cell-free preparation experimental_model: Purified human SARM1 TIR domain; HPLC and LC-MS/MS limitations: Purified engineered TIR fragment rather than basal activity of intact full-length SARM1; no dietary dose inference. exposure: NAD+ incubation cross_nutrient: false evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/sarm2017.txt", "locator": "Full text, normalized paragraph 24", "start_char": 15550, "end_char": 16946, "file_sha256": "fc30de231911f5c30425173d684495e62c725ba27c78d44592e6bc68433ef545", "text_sha256": "9a9b91a772186c34d8b6305a04bbcf6d3acc40b0448e6f478811527c5174981e"} [b3-cons-sarm2017] The SARM1 Toll/Interleukin-1 Receptor Domain Possesses Intrinsic NAD+ Cleavage Activity that Promotes Pathological Axonal Degeneration. (2017). https://pubmed.ncbi.nlm.nih.gov/28334607/ DOI: 10.1016/j.neuron.2017.02.022
Complete structured claim and evidence
PARP1 with HPF1 and NAD+ ADP-ribosylated histone H3 at serines 10 and 28 in reconstituted assays.
Human PARP1 → Histone H3 serine ADP-ribosylation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/niacin-consumption-sources/parp2017.txt", "locator": "Full text, normalized paragraph 33", "start_char": 8991, "end_char": 10338, "file_sha256": "8195abaa884a41856a21fb1d4e7ee376ce80424f11f4625ca4d597a717cef30e", "text_sha256": "ce51127814506d2aa745261fa114922afd3585ee7a97be6fc1cf3914c6609789"}
experimental_model
Recombinant human PARP/HPF1 and histone substrate reconstitution with mass spectrometry
exposure
Activated DNA and NAD+; HPF1 addition
limitations
Direct in vitro modification; protein-bound serine is not a free dietary substrate. No vitamin intake or clinical benefit measured.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human
plain_language
PARP1 uses NAD to add ADP-ribose to histone serines when HPF1 is present.
primary_references
[b3-cons-parp2017] Serine ADP-Ribosylation Depends on HPF1. (2017). https://pubmed.ncbi.nlm.nih.gov/28190768/ DOI: 10.1016/j.molcel.2017.01.003
tissue_or_cell_type
Cell-free histone assay
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 635–647
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PARP/HPF1 and histone substrate reconstitution with mass spectrometry · source_derived_draft · unverified_draft
### b3-cons-parp1-h3-serine PARP1 with HPF1 and NAD+ ADP-ribosylated histone H3 at serines 10 and 28 in reconstituted assays. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: PARP1 uses NAD to add ADP-ribose to histone serines when HPF1 is present. organism: Human tissue_or_cell_type: Cell-free histone assay experimental_model: Recombinant human PARP/HPF1 and histone substrate reconstitution with mass spectrometry limitations: Direct in vitro modification; protein-bound serine is not a free dietary substrate. No vitamin intake or clinical benefit measured. exposure: Activated DNA and NAD+; HPF1 addition cross_nutrient: false evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/parp2017.txt", "locator": "Full text, normalized paragraph 33", "start_char": 8991, "end_char": 10338, "file_sha256": "8195abaa884a41856a21fb1d4e7ee376ce80424f11f4625ca4d597a717cef30e", "text_sha256": "ce51127814506d2aa745261fa114922afd3585ee7a97be6fc1cf3914c6609789"} [b3-cons-parp2017] Serine ADP-Ribosylation Depends on HPF1. (2017). https://pubmed.ncbi.nlm.nih.gov/28190768/ DOI: 10.1016/j.molcel.2017.01.003
Complete structured claim and evidence
Human SIRT1 removes acetylation from histone H4 Lys16 in an NAD+-dependent reaction.
SIRT1 → Histone H4 acetylated at K16 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human enzyme assays and cultured-cell SIRT1 perturbation.
limitations
This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.
organism
Human
plain_language
A different enzyme removes a lysine modification using NAD+.
primary_references
[sirt1-2004] Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin (2004). https://pubmed.ncbi.nlm.nih.gov/15469825/ DOI: 10.1016/j.molcel.2004.08.031
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 537–545
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme assays and cultured-cell SIRT1 perturbation. · source_derived_draft · unverified_draft
### sirt1-h4k16-deacetylation Human SIRT1 removes acetylation from histone H4 Lys16 in an NAD+-dependent reaction. Plain language: A different enzyme removes a lysine modification using NAD+. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human enzyme assays and cultured-cell SIRT1 perturbation. limitations: This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [sirt1-2004] Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin (2004). https://pubmed.ncbi.nlm.nih.gov/15469825/ DOI: 10.1016/j.molcel.2004.08.031
Complete structured claim and evidence
NNMT transfers a methyl group from SAM to nicotinamide, yielding N1-methylnicotinamide and S-adenosylhomocysteine.
Human NNMT → N1-Methylnicotinamide source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 8", "start_char": 2396, "end_char": 4508, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "fc5cdd48751fa59656f5c16e70c31ab3f36788c265267d7cb57f269bb1848fc6"}
experimental_model
Human cancer-cell enzyme activity and metabolomics study
exposure
Nicotinamide substrate and NNMT expression/activity comparisons
limitations
Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human
plain_language
Nicotinamide methylation uses a methyl group from SAM.
primary_references
[b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204
tissue_or_cell_type
769P, OVCAR3, MUM2C and comparison cell models
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 747–759
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cancer-cell enzyme activity and metabolomics study · source_derived_draft · unverified_draft
### b3-cons-nnmt-methyl-transfer NNMT transfers a methyl group from SAM to nicotinamide, yielding N1-methylnicotinamide and S-adenosylhomocysteine. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotinamide methylation uses a methyl group from SAM. organism: Human tissue_or_cell_type: 769P, OVCAR3, MUM2C and comparison cell models experimental_model: Human cancer-cell enzyme activity and metabolomics study limitations: Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements. exposure: Nicotinamide substrate and NNMT expression/activity comparisons cross_nutrient: true evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 8", "start_char": 2396, "end_char": 4508, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "fc5cdd48751fa59656f5c16e70c31ab3f36788c265267d7cb57f269bb1848fc6"} [b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204
Complete structured claim and evidence
In 769P cells cultured with 10 micromolar methionine, NNMT overexpression significantly lowered SAM relative to control cells.
Human NNMT → Cellular S-adenosylmethionine concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 24", "start_char": 12788, "end_char": 14928, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "760641ee47babbc4c1261afe881ea4baa14ae9032d0538bd467c9957224059f7"}
experimental_model
Targeted LC-MS metabolomics
exposure
NNMT overexpression versus GFP/inactive Y20A controls in 10 micromolar methionine medium
limitations
Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements. Low medium methionine is an experimental exposure, not diagnosed human methionine or niacin deficiency.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human
plain_language
SAM fell when these NNMT-rich cancer cells were cultured with less methionine.
primary_references
[b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204
tissue_or_cell_type
Human 769P renal carcinoma cells
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 789–801
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted LC-MS metabolomics · source_derived_draft · unverified_draft
### b3-cons-nnmt-sam-low-methionine In 769P cells cultured with 10 micromolar methionine, NNMT overexpression significantly lowered SAM relative to control cells. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: SAM fell when these NNMT-rich cancer cells were cultured with less methionine. organism: Human tissue_or_cell_type: Human 769P renal carcinoma cells experimental_model: Targeted LC-MS metabolomics limitations: Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements. Low medium methionine is an experimental exposure, not diagnosed human methionine or niacin deficiency. exposure: NNMT overexpression versus GFP/inactive Y20A controls in 10 micromolar methionine medium cross_nutrient: true evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 24", "start_char": 12788, "end_char": 14928, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "760641ee47babbc4c1261afe881ea4baa14ae9032d0538bd467c9957224059f7"} [b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204
Complete structured claim and evidence
At standard 100 micromolar medium methionine, NNMT overexpression changed SAM by less than 1.5-fold despite increased SAH.
Human NNMT → Cellular S-adenosylmethionine concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 24", "start_char": 12788, "end_char": 14928, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "760641ee47babbc4c1261afe881ea4baa14ae9032d0538bd467c9957224059f7"}
experimental_model
Targeted LC-MS metabolomics
exposure
100 micromolar methionine culture medium; NNMT overexpression
limitations
Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Human
plain_language
A higher methyl-transfer product did not necessarily mean a large fall in SAM.
primary_references
[b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204
tissue_or_cell_type
Human cancer-cell overexpression models
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 775–787
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted LC-MS metabolomics · source_derived_draft · unverified_draft
### b3-cons-nnmt-sam-standard At standard 100 micromolar medium methionine, NNMT overexpression changed SAM by less than 1.5-fold despite increased SAH. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A higher methyl-transfer product did not necessarily mean a large fall in SAM. organism: Human tissue_or_cell_type: Human cancer-cell overexpression models experimental_model: Targeted LC-MS metabolomics limitations: Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements. exposure: 100 micromolar methionine culture medium; NNMT overexpression cross_nutrient: true evidence_span: {"source_cache": "artifacts/niacin-consumption-sources/nnmt2013.txt", "locator": "Full text, normalized paragraph 24", "start_char": 12788, "end_char": 14928, "file_sha256": "7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca", "text_sha256": "760641ee47babbc4c1261afe881ea4baa14ae9032d0538bd467c9957224059f7"} [b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204
Complete structured claim and evidence
Human DHPS binds NAD and spermidine; NAD-dependent chemistry initiates aminobutyl transfer.
NAD+ → DHPS source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Purified human DHPS crystallography and single-turnover assays.
limitations
NAD is regenerated during the reaction; this does not measure NAD depletion or establish niacin supplementation benefit.
nutrient_topic
Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Spermidine
plain_language
A niacin-derived coenzyme participates in using spermidine.
primary_references
Half Way to Hypusine-Structural Basis for Substrate Recognition by Human Deoxyhypusine Synthase. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32235505/ · DOI 10.3390/biom10040522
Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 14–20
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human DHPS crystallography and single-turnover assays. · source_derived_draft · unverified_draft
## spermidine-dhps-nad A niacin-derived coenzyme participates in using spermidine. Human DHPS binds NAD and spermidine; NAD-dependent chemistry initiates aminobutyl transfer. Model: Purified human DHPS crystallography and single-turnover assays. Limitations: NAD is regenerated during the reaction; this does not measure NAD depletion or establish niacin supplementation benefit. Evidence access: Primary full text Half Way to Hypusine-Structural Basis for Substrate Recognition by Human Deoxyhypusine Synthase. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32235505/ · DOI 10.3390/biom10040522
Complete structured claim and evidence
Human ISYNA1 used NAD+ in its catalytic assay, with a reported apparent Km of 8 micromolar.
NAD+ → ISYNA1 (human inositol-3-phosphate synthase 1) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/15024000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac", "start_char": 0, "end_char": 1427, "text_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac"}
experimental_model
Recombinant human enzyme and complementation of yeast ino1 deletion
exposure
Substrate, NAD+, cation and valproate experiments
limitations
Purified-enzyme and yeast results do not establish supplement effects or a human dietary deficiency threshold.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human protein expressed in bacteria and yeast
plain_language
The synthesis enzyme depends on NAD+, connecting inositol chemistry to the niacin-derived cofactor network.
primary_references
[ino-p15024000] Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast. (2004). https://pubmed.ncbi.nlm.nih.gov/15024000/ DOI: 10.1074/jbc.m312078200
tissue_or_cell_type
Purified enzyme; yeast cultures
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 184–195
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human enzyme and complementation of yeast ino1 deletion · source_derived_draft · unverified_draft
### ino-isyna-nad Human ISYNA1 used NAD+ in its catalytic assay, with a reported apparent Km of 8 micromolar. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The synthesis enzyme depends on NAD+, connecting inositol chemistry to the niacin-derived cofactor network. organism: Human protein expressed in bacteria and yeast tissue_or_cell_type: Purified enzyme; yeast cultures experimental_model: Recombinant human enzyme and complementation of yeast ino1 deletion limitations: Purified-enzyme and yeast results do not establish supplement effects or a human dietary deficiency threshold. exposure: Substrate, NAD+, cation and valproate experiments evidence_span: {"source_cache": "artifacts/inositol-research/15024000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac", "start_char": 0, "end_char": 1427, "text_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac"} [ino-p15024000] Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast. (2004). https://pubmed.ncbi.nlm.nih.gov/15024000/ DOI: 10.1074/jbc.m312078200
Complete structured claim and evidence
The XDH form transfers purine-derived electrons through its iron-sulfur centers and FAD to NAD+, producing NADH.
Human xanthine oxidoreductase / XDH → NAD+ source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/molybdenum-research/37713777.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8092b2aa7328b59f0275dd8a37d2a2dbb5abb2a32236d0cab5fffcc1ddc671d", "start_char": 0, "end_char": 1579, "text_sha256": "18325172be489f8f4beae16c04dbc4f49f94c87186321e32aede61f27089c7c4"}
experimental_model
Recombinant human XDH variants with urate, superoxide and NO assays
exposure
Xanthine, oxygen and inorganic nitrite assays
limitations
Canonical electron-transfer mechanism stated in this primary article; not an experiment on dietary B2 or niacin depletion.
nutrient_topic
Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum
organism
Homo sapiens protein
plain_language
Riboflavin-derived FAD, iron-sulfur centers and niacin-derived NAD work alongside molybdenum.
primary_references
[mo-p37713777] Natural mutations of human XDH promote the nitrite (NO2-)-reductase capacity of xanthine oxidoreductase: A novel mechanism to promote redox health? (2023). https://pubmed.ncbi.nlm.nih.gov/37713777/ DOI: 10.1016/j.redox.2023.102864
tissue_or_cell_type
Purified human enzyme
Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 768–779
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human XDH variants with urate, superoxide and NO assays · source_derived_draft · unverified_draft
### mo-xdh-nad The XDH form transfers purine-derived electrons through its iron-sulfur centers and FAD to NAD+, producing NADH. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Riboflavin-derived FAD, iron-sulfur centers and niacin-derived NAD work alongside molybdenum. organism: Homo sapiens protein tissue_or_cell_type: Purified human enzyme experimental_model: Recombinant human XDH variants with urate, superoxide and NO assays limitations: Canonical electron-transfer mechanism stated in this primary article; not an experiment on dietary B2 or niacin depletion. exposure: Xanthine, oxygen and inorganic nitrite assays evidence_span: {"source_cache": "artifacts/molybdenum-research/37713777.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8092b2aa7328b59f0275dd8a37d2a2dbb5abb2a32236d0cab5fffcc1ddc671d", "start_char": 0, "end_char": 1579, "text_sha256": "18325172be489f8f4beae16c04dbc4f49f94c87186321e32aede61f27089c7c4"} [mo-p37713777] Natural mutations of human XDH promote the nitrite (NO2-)-reductase capacity of xanthine oxidoreductase: A novel mechanism to promote redox health? (2023). https://pubmed.ncbi.nlm.nih.gov/37713777/ DOI: 10.1016/j.redox.2023.102864
Complete structured claim and evidence
In the resveratrol study, human TyrRS stimulated NAD-dependent PARP1 auto-poly-ADP-ribosylation in biochemical experiments.
Human cytosolic tyrosyl-tRNA synthetase / YARS1 → Human PARP1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Purified-protein interaction/activation assays.
limitations
Greater PARylation need not imply greater net NAD stores.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
This signaling step consumes a niacin-derived cofactor.
primary_references
A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 302–308
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified-protein interaction/activation assays. · source_derived_draft · unverified_draft
## resveratrol-tyrrs-parp This signaling step consumes a niacin-derived cofactor. In the resveratrol study, human TyrRS stimulated NAD-dependent PARP1 auto-poly-ADP-ribosylation in biochemical experiments. Model: Purified-protein interaction/activation assays. Limitations: Greater PARylation need not imply greater net NAD stores. Evidence access: Primary full text A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Complete structured claim and evidence
NAD depletion with NAMPT inhibitor STF-118804 abolished resveratrol-mediated induction of BRCA1, FOXO3A, NAMPT, SESN2 and SIRT6 in human HeLa cells.
Human nicotinamide phosphoribosyltransferase / NAMPT → Resveratrol-induced stress-protein response in human HeLa cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Pharmacological NAMPT inhibition.
limitations
This does not prove supplementation with niacin, NR or NMN improves the response.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
The response needs functioning NAD salvage machinery.
primary_references
A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
trigger_kind
machinery_impairment Imported condition classification; unverified.
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 334–340
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pharmacological NAMPT inhibition. · source_derived_draft · unverified_draft
## resveratrol-nampt-block The response needs functioning NAD salvage machinery. NAD depletion with NAMPT inhibitor STF-118804 abolished resveratrol-mediated induction of BRCA1, FOXO3A, NAMPT, SESN2 and SIRT6 in human HeLa cells. Model: Pharmacological NAMPT inhibition. Limitations: This does not prove supplementation with niacin, NR or NMN improves the response. Evidence access: Primary full text A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Complete structured claim and evidence
Silencing PARP1 abolished the one-hour NAD increase induced by low-dose resveratrol in human HeLa cells.
Human PARP1 → NAD content in human HeLa cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
siRNA experiments; 5 micromolar resveratrol.
limitations
Cell-model dependency, not a dietary resveratrol-deficiency state.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
Removing a signaling component prevented the rebound.
primary_references
A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
trigger_kind
machinery_impairment Imported condition classification; unverified.
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 326–332
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · siRNA experiments; 5 micromolar resveratrol. · source_derived_draft · unverified_draft
## resveratrol-parp-loss Removing a signaling component prevented the rebound. Silencing PARP1 abolished the one-hour NAD increase induced by low-dose resveratrol in human HeLa cells. Model: siRNA experiments; 5 micromolar resveratrol. Limitations: Cell-model dependency, not a dietary resveratrol-deficiency state. Evidence access: Primary full text A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Complete structured claim and evidence
Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD.
DLD → Protein-bound reduced dihydrolipoyl-lysine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction.
evidence
[{"paper_key": "brautigam-2005-dld", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human DLD crystallography with NAD+ and NADH.
limitations
Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover.
primary_references
[brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014
tissue_or_cell_type
Purified enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 717–729
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DLD crystallography with NAD+ and NADH. · source_derived_draft · unverified_draft
### b1-dld-fad-nad-lipoyl-regeneration Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Human DLD crystallography with NAD+ and NADH. limitations: Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency. evidence: [{"paper_key": "brautigam-2005-dld", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction. nutrient: Thiamine (vitamin B1) [brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014
Complete structured claim and evidence
Human OGDH, lipoylated DLST and DLD assembled into an active complex coupling 2-oxoglutarate oxidation to NADH production in the CoA-containing assay.
2-Oxoglutarate dehydrogenase complex → Succinyl-CoA source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1, B5-derived CoA, B2-derived FAD and niacin-related NAD act at different steps of one complex.
evidence
[{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-28"], "locator": "The reaction medium contained the following in 1.0 ml", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Reconstituted human multienzyme assay.
limitations
NADH assay measures overall complex turnover, not every intermediate independently.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1-dependent E1 feeds a lipoyl/CoA transfer pathway, and E3 transfers the resulting reducing equivalents to NAD.
primary_references
[nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073
tissue_or_cell_type
Purified enzyme complex
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 855–867
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted human multienzyme assay. · source_derived_draft · unverified_draft
### b1-ogdh-complex-couples-succinyl-nadh Human OGDH, lipoylated DLST and DLD assembled into an active complex coupling 2-oxoglutarate oxidation to NADH production in the CoA-containing assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1-dependent E1 feeds a lipoyl/CoA transfer pathway, and E3 transfers the resulting reducing equivalents to NAD. organism: Homo sapiens tissue_or_cell_type: Purified enzyme complex experimental_model: Reconstituted human multienzyme assay. limitations: NADH assay measures overall complex turnover, not every intermediate independently. evidence: [{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-28"], "locator": "The reaction medium contained the following in 1.0 ml", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1, B5-derived CoA, B2-derived FAD and niacin-related NAD act at different steps of one complex. nutrient: Thiamine (vitamin B1) [nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073
Complete structured claim and evidence
Human KYNU cleaves 3-hydroxykynurenine to 3-hydroxyanthranilate and alanine using PLP.
Human kynureninase / KYNU → 3-Hydroxy-L-kynurenine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
PLP-dependent KYNU follows the FAD-dependent KMO step, connecting B6 and B2 with tryptophan-niacin metabolism.
existing_related_claim_ids
["5570a502-6ebf-5397-bf2a-0148727e7695"]
experimental_model
Recombinant human KYNU crystallography and biochemical characterization
limitations
KYNU does not directly make NAD; subsequent enzymes and dietary niacin also contribute.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This B6-dependent step processes the product of upstream KMO chemistry.
primary_references
[b6-kynu-2007] Crystal Structure of Homo Sapiens Kynureninase (2007). https://pmc.ncbi.nlm.nih.gov/articles/PMC2531291/ DOI: 10.1021/bi0616697
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 885–896
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human KYNU crystallography and biochemical characterization · source_derived_draft · unverified_draft
### b6-met-kynu-hydrolysis Human KYNU cleaves 3-hydroxykynurenine to 3-hydroxyanthranilate and alanine using PLP. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B6-dependent step processes the product of upstream KMO chemistry. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human KYNU crystallography and biochemical characterization limitations: KYNU does not directly make NAD; subsequent enzymes and dietary niacin also contribute. cross_nutrient: PLP-dependent KYNU follows the FAD-dependent KMO step, connecting B6 and B2 with tryptophan-niacin metabolism. existing_related_claim_ids: ["5570a502-6ebf-5397-bf2a-0148727e7695"] [b6-kynu-2007] Crystal Structure of Homo Sapiens Kynureninase (2007). https://pmc.ncbi.nlm.nih.gov/articles/PMC2531291/ DOI: 10.1021/bi0616697
Complete structured claim and evidence
Qprt-heterozygous mice had higher quinolinate, lower NAD and greater acute kidney injury susceptibility.
Mouse quinolinate phosphoribosyltransferase / Qprt → Mouse acute kidney injury susceptibility source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse Qprt heterozygous deletion.
limitations
No inference that more tryptophan fixes the blocked step.
nutrient_topic
Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
plain_language
Less conversion machinery increased vulnerability despite accumulated precursor.
primary_references
De novo NAD+ biosynthetic impairment in acute kidney injury in humans. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30127395/ · DOI 10.1038/s41591-018-0138-z
trigger_kind
machinery_impairment Imported condition classification; unverified.
Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 250–256
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse Qprt heterozygous deletion. · source_derived_draft · unverified_draft
## tryptophan-qprt-dosage Less conversion machinery increased vulnerability despite accumulated precursor. Qprt-heterozygous mice had higher quinolinate, lower NAD and greater acute kidney injury susceptibility. Model: Mouse Qprt heterozygous deletion. Limitations: No inference that more tryptophan fixes the blocked step. Evidence access: Primary abstract De novo NAD+ biosynthetic impairment in acute kidney injury in humans. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30127395/ · DOI 10.1038/s41591-018-0138-z
Complete structured claim and evidence
Mouse acute kidney injury reduced renal QPRT and NAD while quinolinate accumulated.
Mouse quinolinate phosphoribosyltransferase / Qprt → Mouse renal NAD abundance source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse acute kidney injury measurements.
limitations
Co-occurrence alone is not the complete causal test; Qprt dosage manipulation is recorded separately.
nutrient_topic
Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
plain_language
An upstream metabolite can rise while the useful downstream product falls.
primary_references
De novo NAD+ biosynthetic impairment in acute kidney injury in humans. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30127395/ · DOI 10.1038/s41591-018-0138-z
trigger_kind
machinery_impairment Imported condition classification; unverified.
Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 242–248
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse acute kidney injury measurements. · source_derived_draft · unverified_draft
## tryptophan-qprt-injury An upstream metabolite can rise while the useful downstream product falls. Mouse acute kidney injury reduced renal QPRT and NAD while quinolinate accumulated. Model: Mouse acute kidney injury measurements. Limitations: Co-occurrence alone is not the complete causal test; Qprt dosage manipulation is recorded separately. Evidence access: Primary abstract De novo NAD+ biosynthetic impairment in acute kidney injury in humans. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30127395/ · DOI 10.1038/s41591-018-0138-z
Complete structured claim and evidence
Oral nicotinamide riboside increased the measured cardiac NAD+ pool in the two-hit HFpEF study.
Nicotinamide riboside → Mouse cardiac NAD+ pool source_derived_draftungraded
Experimental context and source evidence
access_level
full_text_and_supplement_review
compartment
Cardiac tissue / mitochondria
dose
400 mg/kg/day
duration
Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative
endpoint
mouse-cardiac-nad-pool
evidence_location
NAD+ assay kit; Figure 2I
experimental_model
Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated
exposure
nicotinamide-riboside
limitations
Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · NAD+
organism
Mus musculus
plain_language
Oral nicotinamide riboside increased the measured cardiac NAD+ pool in the two-hit HFpEF study.
primary_locator
[{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}]
primary_references
https://doi.org/10.1038/s41467-026-70703-w
route
Oral gavage
sample_size
6 per group
tissue_or_cell_type
Cardiac tissue and cardiomyocytes
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 513–529
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated · source_derived_draft · unverified_draft
Oral nicotinamide riboside increased the measured cardiac NAD+ pool in the two-hit HFpEF study. organism: Mus musculus tissue_or_cell_type: Cardiac tissue and cardiomyocytes experimental_model: Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated compartment: Cardiac tissue / mitochondria dose: 400 mg/kg/day duration: Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative route: Oral gavage primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: NAD+ assay kit; Figure 2I endpoint: mouse-cardiac-nad-pool exposure: nicotinamide-riboside limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}] plain_language: Oral nicotinamide riboside increased the measured cardiac NAD+ pool in the two-hit HFpEF study. sample_size: 6 per group
Complete structured claim and evidence
Nicotinamide riboside supplementation reduced HADHA acetylation in HFpEF mouse hearts.
Nicotinamide riboside → Mouse cardiac HADHA lysine acetylation source_derived_draftungraded
Experimental context and source evidence
access_level
full_text_and_supplement_review
compartment
Cardiac tissue / mitochondria
dose
400 mg/kg/day
duration
Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative
endpoint
mouse-hadha-acetylation
evidence_location
IP/immunoblot; Figure 2L
experimental_model
Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated
exposure
nicotinamide-riboside
limitations
Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. The experiment does not establish selective direct NR action on HADHA or prove SIRT3 is the only mediator.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · NAD+
organism
Mus musculus
plain_language
Nicotinamide riboside supplementation reduced HADHA acetylation in HFpEF mouse hearts.
primary_locator
[{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}]
primary_references
https://doi.org/10.1038/s41467-026-70703-w
route
Oral gavage
sample_size
3 per group
tissue_or_cell_type
Cardiac tissue and cardiomyocytes
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 532–548
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated · source_derived_draft · unverified_draft
Nicotinamide riboside supplementation reduced HADHA acetylation in HFpEF mouse hearts. organism: Mus musculus tissue_or_cell_type: Cardiac tissue and cardiomyocytes experimental_model: Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated compartment: Cardiac tissue / mitochondria dose: 400 mg/kg/day duration: Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative route: Oral gavage primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: IP/immunoblot; Figure 2L endpoint: mouse-hadha-acetylation exposure: nicotinamide-riboside limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. The experiment does not establish selective direct NR action on HADHA or prove SIRT3 is the only mediator. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}] plain_language: Nicotinamide riboside supplementation reduced HADHA acetylation in HFpEF mouse hearts. sample_size: 3 per group
Complete structured claim and evidence
Nicotinamide riboside improved substrate-supported respiration in HFpEF mouse hearts.
Nicotinamide riboside → Mouse cardiac fatty-acid oxidation capacity source_derived_draftungraded
Experimental context and source evidence
access_level
full_text_and_supplement_review
compartment
Cardiac tissue / mitochondria
dose
400 mg/kg/day
duration
Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative
endpoint
mouse-cardiac-fao
evidence_location
Figure 2M–O
experimental_model
Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated
exposure
nicotinamide-riboside
limitations
Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Mouse pharmacological exposure, not a human supplement efficacy or dose claim.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · NAD+
organism
Mus musculus
plain_language
Nicotinamide riboside improved substrate-supported respiration in HFpEF mouse hearts.
primary_locator
[{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}]
primary_references
https://doi.org/10.1038/s41467-026-70703-w
route
Oral gavage
sample_size
4 biological replicates
tissue_or_cell_type
Cardiac tissue and cardiomyocytes
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 551–567
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated · source_derived_draft · unverified_draft
Nicotinamide riboside improved substrate-supported respiration in HFpEF mouse hearts. organism: Mus musculus tissue_or_cell_type: Cardiac tissue and cardiomyocytes experimental_model: Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated compartment: Cardiac tissue / mitochondria dose: 400 mg/kg/day duration: Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative route: Oral gavage primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: Figure 2M–O endpoint: mouse-cardiac-fao exposure: nicotinamide-riboside limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Mouse pharmacological exposure, not a human supplement efficacy or dose claim. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}] plain_language: Nicotinamide riboside improved substrate-supported respiration in HFpEF mouse hearts. sample_size: 4 biological replicates
Complete structured claim and evidence
Nicotinamide riboside improved the reported diastolic phenotype in the mouse HFpEF model.
Nicotinamide riboside → Mouse cardiac diastolic impairment source_derived_draftungraded
Experimental context and source evidence
access_level
full_text_and_supplement_review
compartment
Cardiac tissue / mitochondria
dose
400 mg/kg/day
duration
Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative
endpoint
mouse-cardiac-diastolic-impairment
evidence_location
Supplementary Figure S6
experimental_model
Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated
exposure
nicotinamide-riboside
limitations
Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Systemic metabolic effects can contribute; no human efficacy inference.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · NAD+
organism
Mus musculus
plain_language
Nicotinamide riboside improved the reported diastolic phenotype in the mouse HFpEF model.
primary_locator
[{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}]
primary_references
https://doi.org/10.1038/s41467-026-70703-w
route
Oral gavage
tissue_or_cell_type
Cardiac tissue and cardiomyocytes
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 570–585
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated · source_derived_draft · unverified_draft
Nicotinamide riboside improved the reported diastolic phenotype in the mouse HFpEF model. organism: Mus musculus tissue_or_cell_type: Cardiac tissue and cardiomyocytes experimental_model: Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated compartment: Cardiac tissue / mitochondria dose: 400 mg/kg/day duration: Figure 2 treatment timeline; exact intervention duration not independently resolved from narrative route: Oral gavage primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: Supplementary Figure S6 endpoint: mouse-cardiac-diastolic-impairment exposure: nicotinamide-riboside limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Systemic metabolic effects can contribute; no human efficacy inference. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 26, "text_sha256": "61dd26202087c725d9dc65345339778ed43192b3f765d05fa8a311a6e1944b34", "xml_element_id": "Par11"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 72, "text_sha256": "2b1ada63fe6c48d4296bbfb14a97940ac4a866b1d5171b0923851ec72f88ab15", "xml_element_id": "Par31"}] plain_language: Nicotinamide riboside improved the reported diastolic phenotype in the mouse HFpEF model.
Complete structured claim and evidence
NR co-treatment opposed the impaired FAO-associated respiration in the 3-TYP rat-cell experiment.
Nicotinamide riboside → Rat cardiac fatty-acid oxidation capacity source_derived_draftungraded
Experimental context and source evidence
access_level
full_text_and_supplement_review
compartment
Mitochondria or cell lysate, depending on assay
dose
Compound concentration not established in reviewed text
duration
Treatment endpoint timing not established in reviewed text
endpoint
rat-cardiac-fao
evidence_location
Figure 2A–G
experimental_model
Pharmacological 3-TYP experiment; NR co-treatment where stated
exposure
nicotinamide-riboside
limitations
Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. The figure tests 3-TYP plus NR; do not mislabel it as an NR-alone dose-response experiment.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · NAD+
organism
Rattus norvegicus host cells; construct species may be unspecified
plain_language
NR co-treatment opposed the impaired FAO-associated respiration in the 3-TYP rat-cell experiment.
primary_locator
[{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 23, "text_sha256": "08f11746524e975c9e1a5e3d53de363a6762891bc05afffbd711f347867ac842", "xml_element_id": "Par10"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}]
primary_references
https://doi.org/10.1038/s41467-026-70703-w
sample_size
4 respiratory replicates; 6 staining replicates
tissue_or_cell_type
Neonatal rat ventricular cardiomyocytes (NRVCMs)
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 623–638
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Pharmacological 3-TYP experiment; NR co-treatment where stated · source_derived_draft · unverified_draft
NR co-treatment opposed the impaired FAO-associated respiration in the 3-TYP rat-cell experiment. organism: Rattus norvegicus host cells; construct species may be unspecified tissue_or_cell_type: Neonatal rat ventricular cardiomyocytes (NRVCMs) experimental_model: Pharmacological 3-TYP experiment; NR co-treatment where stated compartment: Mitochondria or cell lysate, depending on assay dose: Compound concentration not established in reviewed text duration: Treatment endpoint timing not established in reviewed text primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: Figure 2A–G endpoint: rat-cardiac-fao exposure: nicotinamide-riboside limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. The figure tests 3-TYP plus NR; do not mislabel it as an NR-alone dose-response experiment. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 23, "text_sha256": "08f11746524e975c9e1a5e3d53de363a6762891bc05afffbd711f347867ac842", "xml_element_id": "Par10"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 25, "text_sha256": "1814242d6194ed4e0b3ab78287e20f85b6bc243051183d0f24d9034c3a930257", "xml_element_id": null}] plain_language: NR co-treatment opposed the impaired FAO-associated respiration in the 3-TYP rat-cell experiment. sample_size: 4 respiratory replicates; 6 staining replicates
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

Salvage blockade exposes compartment-specific consumption

Condition: machinery_impairment · NAMPT inhibition in cultured human cells.